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Notes: Summary Projections of the somesthetic ascending pathways to the superior colliculus (SC) of the cat have been demonstrated by means of the horseradish peroxidase (HRP) tracing technique. Following HRP injection in one SC, marked neurons were found in the contralateral dorsal horn and in the contralateral dorsal column nuclei, mainly the cuneate nucleus. Moreover, in the contralateral trigeminal complex, the sub-nucleus caudalis of the spinal nucleus of the Vth nerve, and the subnucleus oralis plus the main sensory trigeminal nucleus were labeled. Thus, the anterolateral system and the lemniscal system subserving face and forelimb sensation send afferent fibers to the contralateral SC.

Notes: Summary In the cat caudate nucleus the same nine types of synapses are found as in putamen and fundus striati. The three parts of the striatum in the strict sense do not differ in the morphological differentiation of synapse types but only in their quantitative distribution. One-third of all synapses in the caudate nucleus are axo-spinous type IV synapses with a curved and divided asymmetric contact. This strongly suggests that the caudate nucleus interneuronal apparatus is dominated by centre-median input, in contrast to the putamen which is controlled by the cortico-striatal input to its internuncial cells and by its strong intrastriatal feedback mechanism. Extensive destruction of the convexity of the cortex and the medial cortex in one hemisphere results in dark degeneration of a large proportion of two of the nine types of caudate synapses: a) the axo-dendritic type VII synapses exciting the large aspiny caudate neurons and b) the axo-spinous type III synapses making contact with the small spiny neurons of the interneuronal cell apparatus.

Notes: Summary Retrograde tracing experiments using horseradish peroxidase (HRP) have been utilized for demonstrating the origin of efferent projections of the ventral lateral geniculate nucleus (LGNv) in the cat. HRP-positive cells identifiable as origins of thalamic projections were found in LGNv after injections of HRP into the lateral central intralaminar nucleus. The labeled cells appeared concentrated in the medial part of the internal division of LGNv, consisting of medium-sized multipolar cells. Contralaterally, fewer labeled cells were present in the corresponding part of LGNv. In the case of injections of HRP into the midbrain (pretectum and superior colliculus), labeled cells in LGNv were distributed almost exclusively in its external division, composed of mainly small cells. Little overlap of the distribution of HRP-positive cells was seen in LGNv between the thalamic and midbrain injection cases.

Notes: Summary It has previously been shown that unilateral ablation of the whole auditory cortex in the cat disrupts the precedence effect, and also interferes with the ability of the normal animal to discriminate in the Y-maze between a single sound on one side and a double sound consisting of a signal on both left and right sides. The present work has confirmed these effects and has shown that both can be obtained with lesions confined to AI and AII The ‘one-versus-two’ deficit has invariably been seen in all the animals studied, but a proportion of animals do not show the precedence effect deficit. It has been confirmed that the apparent success of some animals can be due to the training effect of the one-versus-two paradigm, as was proposed in the earlier paper; however it has also been shown that this cannot be the explanation in all cases. It has been demonstrated that cats are able to localize sounds behind them with some success; turning around in the start box to reverse right and left space is therefore a possible strategy for overcoming a unilateral deficit. However, even with the head ‘fixed’ in the forward-facing position, one animal was still able to run well above chance. The size of the lesion does not appear to be a correlate of the performance level.

Notes: Summary Electron microscopical studies of the thalamic AV-AM nuclei substantiated the presence of two main types of neurons, i.e. principal (or relay) cells and Golgi type II interneurons. Characteristic synaptic islands are found in abundance in the AV-AM. Four different types of synaptic terminals have been identified in these islands: RL-boutons = large axonal terminals with round synaptic vesicles; RS-boutons = small axonal terminals with round synaptic vesicles; F1-boutons = small axonal profiles containing flattened synaptic vesicles, and F2-profiles interpreted as presynaptic dendrite appendages, bearing pleomorphic vesicles, both belonging to the Golgi type II interneurons. — The synaptic relations were studied in normal preparations and after lesions in the mamillary body, limbic cortex and hippocampus. The specific afferents (RL-boutons) — originating from the medial mamillary nucleus — are presynaptic to both relay cell dendrites and “presynaptic” dendrite profiles of Golgi type II interneurons, which in turn are presynaptic to the same relay dendrites (synaptic triads). RS-boutons originate mainly from limbic cortex and hippocampus.

Notes: Summary A sudden and rapid angular displacement of the limb evokes, in human and monkey subjects, a segmented pattern of electromyographic activity in muscles which are stretched. While the first segment is acknowledged to represent a tendon jerk, it has been proposed that the second segment, occurring with a shorter latency than a reaction time, is mediated by a transcortical loop. The present experiments were conducted in cats to determine the properties of muscle responses to torque perturbations analogous to those used in the monkey, and to determine if the integrity of supraspinal pathways is required for the individual response segments to occur. Torque perturbations which flexed the forearm evoked a segmented response in the electromyogram of the cat triceps muscle. This response typically consisted of three early segments with latencies of 10, 30 and 60 msec which were similar to the M1, M2, and M3 segments described in the monkey. The M3 and occasionally M2 components were depressed when the cat followed rather than resisted the perturbation. A torque pulse of 10 msec duration was sufficient to elicit a near maximal M1 response while torque pulses in excess of 20 msec were required to evoke the M2 response. To determine if any of these components required mediation by the cerebral cortex, experiments were conducted in decerebrate and spinal cats. Similar torque perturbations produced segmented electromyographic responses in the triceps muscles which were indistinguishable in their timing from those observed in intact cats. The torque required to produce the segmented responses was comparable as well. All three segments were dependent upon the activation of receptors in the homonymous muscle and did not require cutaneous input. These observations show that receptor properties and/or spinal mechanisms involved in the stretch reflex are sufficient to produce a segmented response similar to that observed in intact animals.

Notes: Summary The ascending and intrinsic projections of the superior olivary complex (SO) in the cat were investigated by injection of 3H-leucine and horseradish peroxidase (HRP) in SO and the inferior colliculus (IC), respectively. A topically arranged projection was demonstrated from the nucleus of the trapezoid body (NTB) to the ipsilateral lateral superior olivary nucleus (LSO) with a lesser connection in the opposite direction. The medial superior olivary nucleus (MSO) has a strictly ipsilateral projection, whilst LSO projects symmetrically through the lateral lemniscus (LL) of both sides, to end with topically arranged terminals in the ventrolateral part of the central nucleus of the inferior colliculus (CNIC). Terminal labelling found in the ventral and dorsal nuclei of LL (VNLL and DNLL) probably represents collaterals from bypassing fibres originating in MSO and LSO, respectively. These results were demonstrated by both techniques, whilst in addition the HRP method revealed an ipsilateral and a contralateral projection to IC from VNLL and DNLL, respectively.

Notes: Summary Single unit recordings were carried out in the reticularis thalamic nucleus (RT) and the ventral lateral geniculate body (LGv) of chronically prepared alert cats under sinusoidal vestibular stimulation in the horizontal plane. Optokinetic stimulation was also used. Of the 57 recorded neurons, 12 present vestibular modulation in the dark, analogous to Duensing's and Schaefer's (1958) type I response in the vestibular nuclei. Responses of 26 cells are similar to response of type II vestibular neurons and 14 units have a type III response; the 5 remaining cells were activated by vestibular stimulation in the vertical sagittal plane. The majority of these cells does not present detectable direct visual responses, but 50% can be driven by Optokinetic stimulation. 74 % of types I, II and III neurons show saccadic responses to vestibular nystagmic saccades in the dark. About 60% present similar saccadic modulations during Optokinetic nystagmus and 55% keep this response for spontaneous saccades in the dark or in front of a striped background. The saccadic responses are constant for a given neuron in all cases of stimulation with latencies ranging from 30 msec prior to the beginning of the saccade to 120 msec after its onset. The histological localization of these units falls on one hand into the caudal part of the RT nucleus (type III neurons) above the dorsal lateral geniculate nucleus and on the other hand within the internal subdivision of the LGv and its rostral limit (all other types). The significance of this new, saccadic and vestibular focus in the feline thalamus is discussed in relation with the two previously known vestibular thalamic relays in terms of interrelations between the vestibular and the visual systems.

Notes: Summary Different areas of the frontal cortex of the cat were injected with small amounts of horseradish peroxidase. The regions of labeled cells in the mediodorsal nucleus of the thalamus (MD) were related to the injected areas. Distinct relations between subdivisions of MD and of the prefrontal cortex were established: a rather large central sector of MD projects to the gyrus proreus and to the anterior parts of the gyri sigmoideus, rectus, and frontalis. A narrow lateral band of anterior MD neurons projects predominantly to an area on both sides of the sulcus praesylvius, whereas a postero-lateral band sends fibers to a region on the ventral anterior sylvian gyrus. The area between the presylvian sulcus and the sylvian gyrus is apparently free of MD afferents, but not of other thalamic afferents. A fourth sector of MD, situated dorsomedially, projects to the middle parts of the gyri rectus and frontalis. And a fifth sector, located ventrally to the dorsomedial MD sector, projects to the ventral part of the gyrus rectus. The established subfields of MD and of the prefrontal cortex are discussed with respect to previous anatomical research in the cat.

Notes: Summary 1. In the cat visual cortex (VC), electrophoretic glutamate application at a depth corresponding to layer VI may have excitatory or inhibitory effects on relay cells of the lateral geniculate nucleus (LGN). Corticofugal excitation was seen, if the receptive field centers (RFCs) of the VC neurons recorded at the application site were within 2.3 ° of the RFCs of the LGN neurons under test. Inhibitory effects were seen if the RFCs of both cells were further apart up to 3.1 °. Glutamate application at more superficial cortical sites had no effect on LGN-neuron activity. 2. Cross-correlation analysis between spontaneous activities of simultaneously recorded VC and LGN neurons revealed excitatory cortico-geniculate connections in 18 pairs with RFCs separated by less than 1.7 °. In 15 pairs the peak latency of the excitation was 2–5 msec (3.4 msec in the average), 3 pairs showed long cortico-geniculate latencies (13–18 msec). The existence of a fast and slow cortico-geniculate system is suggested. 3. Inhibitory cortico-geniculate interaction was demonstrated with cross-correlation analysis in 8 pairs of which 4 had RFCs separated by more than 1.7 °. The onset latency of the inhibition was 2–7 msec except for 2 pairs with about 20 msec latency. 4. Most of the LGN neurons which were affected by cortical glutamate application or which showed an excitatory or inhibitory connection with a VC neuron were sustained cells, while the majority of VC neurons which were recorded in the effective glutamate application sites or which showed a significant interaction with LGN neurons in the cross-correlogram were binocularly driven and complex, with mostly large RFCs (mean diameter 3.5 °). They responded briskly to moving small spots as well as to moving slits. 5. It is concluded that the corticofugal excitatory effect is transmitted through monosynaptic links from VC neurons located in layer VI (complex cell) to LGN relay neurons (mostly sustained-cell) and this system is organized in a precise topographical manner. 6. In an Appendix neuron pairs which showed a positive correlation in the geniculo-cortical direction were described. The findings may support the view that complex as well as simple cells are driven monosynaptically from geniculo-cortical afferents of the sustained or transient type.

Notes: Summary In the anesthetized cat, the posterior canal nerve (PCN) was stimulated by electric pulses and synaptic responses were recorded intracellularly in the three antagonistic pairs of extraocular motoneurons. Pure reciprocal effects were obtained in the motoneurons innervating the antagonistic pair of ipsilateral oblique muscles and the antagonistic pair of contralateral vertical rectus muscles. These responses consisted of low threshold disynaptic excitatory postsynaptic potentials (EPSPs) in either the contralateral superior oblique (c-SO) (trochlear) or contralateral inferior rectus (c-IR) motoneurons and of disynaptic inhibitory postsynaptic potentials (IPSPs) in either the ipsilateral inferior oblique (i-IO) or ipsilateral superior rectus (i-SR) motoneurons. In addition, disynaptic IPSPs were also found in (i-SO) motoneurons. Mixtures of low threshold (dior trisynaptic) EPSPs and IPSPs were found in all other extraocular motoneurons except for the contralateral lateral rectus (c-LR) motoneurons. These results may afford a basis for the characteristic eye movements induced by vertical canal nerve stimulation.

Notes: Summary 1. The activity of cat semicircular canal and otolith afferents was studied during yaw and roll rotations, respectively, to examine their dynamic behavior. 2. A sinusoidal analysis of the canal afferent activities showed that their dynamic characteristics are similar to those of second order vestibular neurons, except for a two to three-fold lower absolute gain. This agrees with earlier studies using angular acceleration steps. 3. Both divisions of the eighth nerve were sampled so as to examine afferents from both the utriculus and sacculus. Within the range of inputs used (± 25 degrees lateral tilt), the presumed saccular afferents (inferior division) showed either a γ- or β-response. However, the gain of their response was generally much less than for the afferents of the superior division (mostly utricular). This behavior is to be expected on the basis of receptor orientations and the components of gravity acting upon the macular receptors. 4. In response to ramp changes in angular position, some otolith units showed a phasic-tonic response pattern, i.e., an overshoot followed by an adaptation to a new steady state level of activity. The majority of units showed predominantly tonic responses proportional to displacement. 5. During sinusoidal rotations the predominantly tonic units showed small phase leads of 0 to 15 degrees at 0.025 Hz which remained constant or decreased to 0 to −15 degrees at 1.0 Hz. The gains were flat or increased by up to 2 fold. The phasic-tonic units showed greater phase leads, 10 to 50 degrees, and gains which increased from 2 to 8 fold. 6. This behavior of otolith afferents suggests that they can provide information about both the magnitude and the rate of change of linear acceleration stimuli.

Notes: Summary 1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the β type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 ° at 0.025 Hz to 126 ° at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 ° and 130 ° at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 °. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 ° (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the responses of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.

Notes: Summary It is known that kittens reared in ways that restrict movement while visual stimulation is received exhibit deficits in visually guided behavior. Presumably, the behavioral dysfunction is due to a lack of sensorimotor coordination during visual exposure. The current investigation was undertaken to study this effect both physiologically and behaviorally. Two groups of kittens were normally reared until they were nearly 4 weeks old. They were then placed in a darkroom and exposed daily for 1–2 hours while one eye was occluded. On alternate days, alternate eyes were covered. One group was restrained in a body cast while a given eye was exposed, but the kittens were free to move about while the other eye received visual experience. A second control group was alternately occluded, but freely mobile during all exposures. An additional cat was also unrestrained during daily rearing periods and neither eye was ever occluded. Behavioral tests showed clear deficits when the “passive” eye of the restrained-unrestrained group was used. Deficiencies were found in visually guided paw placing, pursuit eye movements, and jumping behavior to a platform. Responses of single cells were studied in area 17 of the visual cortex. Ocular dominance distributions showed marked reductions in binocularity for alternate occluder cats. The eye that had received exposure while animals were active in the restrained-unrestrained group also tended to predominate but the difference was not statistically significant.

Notes: Summary In the previous study it was shown that cats were capable of making rapid and accurate adjustments in the force they applied to a lever in accord with information provided by a compensatory display. In the present study, isometric responses were examined in greater detail to determine 1. if a general control policy (or model) governing responses of different magnitudes could be inferred from the relations among output parameters and 2. if the earliest output measures were scaled to the preceding sensory events. The force adjustments elicited by the sudden motion of the display showed a linear relation between the peak force and the peak of its first derivative, dF/dt. Similarly, the peak d2F/dt2 was a linear function of dF/dt. By contrast, the times required to achieve the peak force and the peak dF/dt were largely independent of their magnitudes. These adjustments were produced by a burst of EMG activity in agonist muscles which coincided with the rising phase of dF/dt. The observations suggest that such motor outputs are determined by a pulse-step control policy. The amplitude of the pulse would control the rate of rise of dF/dt (and therefore also the peak force since the rising phase of dF/dt was of constant duration), and the step would control the level of the terminal steady state force. Both the peak force and the preceding peak dF/dt were highly correlated with the amplitude of the perturbation. Changes in display gain, which altered the required relation between input and output magnitudes, resulted in a gradual readjustment of the output parameters. It was concluded that the motor outputs were scaled from their inception to requirements dictated by the initial sensory information. The selection by the cat of the appropriate scaling function was contingent upon its previous experience with the device.

Notes: Summary A versatile tracking task has been developed to assess the competence of feline subjects in using sensory information to initiate and guide limb movement. In the present study we investigated the response latency and the factors which affect it in order to define temporal constraints on the underlying processing of information. The paradigm makes use of an electromechanical display of the difference between the output of transducers in a manipulandum (controlled by the cat) and a target level (controlled by the experimenter). Because of inertia and friction, a step change in target level required 230 msec to fully shift the display. The animals were trained to match the position of the manipulandum (or the force they applied to it isometrically) to the target level for a food reward. Target perturbations elicited rapid position or force adjustments of appropriate direction and magnitude at short latency. Under isometric conditions, the latency of the response was an inverse function of the extent of display motion and of the peak rate of force change attained during the adjustment. Asymptotic values of the response time, measured from the perturbation to the first change in force applied to the lever, were typically between 50 and 70 msec. Since the motor responses were invariably initiated while the display was still moving, the animals must have used information contained in the derivatives of its motion. In the absence of visual cues, deflection of the vibrissae by the sudden motion of the display provided two of the four animals with sufficient information to initiate and guide their movements without changes in response latency. When vision was allowed, section of the vibrissae produced a persistent increase in response times of 15–20 msec. This difference in latency is compatible with the delays due to retinal transmission. The short time interval elapsing between stimulus and response strongly suggests that the topography and the metrics of the underlying transformations are adjusted by gating and/or biasing processes which precede the stimulus. It is concluded that sensory information can generate purposeful movements through pathways which include only a small number of central relays in series, independently of its modality.

Notes: Summary The current source density (CSD) method in its one-dimensional approximation is used to analyze the field potentials in visual areas 18 and 17 of the cat, which were elicited by stimulating electrodes in the optic chiasm (OX), the optic radiation (OR) or in the respective cortical area itself. The CSD analysis reveals the basic pattern of excitatory postsynaptic activity. 1. In both visual areas the basic specific excitatory activity flows along three different intracortical pathways, all starting in layer IV: The first pathway relays activity from layer IV to supragranular pyramidal cells via strong, local connections to layer III and from there through long-distance connections to layer II. The second pathway conveys activity from layer IV to layer V, where it mainly contacts apical dendrites of layer VI pyramidal cells. This infragranular polysynaptic activity is not clearly resolvable into separate components, suggesting that it is conveyed by various groups of axons, among them long-distance horizontal connections. The third pathway has one synaptic relay within layer IV and then conveys activity to layer III. In addition, monosynaptic activity is revealed in layers VI and I. 2. In A 18 one coherent, fast-conducting group of afferents induces this basic activity pattern. In A 17 no such fast conducting input is resolvable; the supragranular activity is induced by a small group of afferents with intermediate conduction velocity, which terminate in the upper part of layer IV. The infragranular activity is induced by afferents with slower and widely scattered conduction velocities, which terminate in the lower part of layer IV. The layer VI input is very prominent in A 17 and also has a wide latency scatter. 3. The supragranular activity is more prominent in A 18 than in A 17 and the respective layers appear thicker, in accordance with anatomy. In A 17 the infragranular activity prevails and layers IV and VI appear very broad, again in accordance with anatomy. 4. Comparison of the CSDs with the original evoked potentials shows that the surface evoked potentials over A 18 reflect the three dipolar sink/source distributions of the coherent monosynaptic activity in layer IV and of the two prominent polysynaptic activities in layers III and II. The widely scattered activity in the lower part of layer IV in A 17 and all infragranular activities in both areas generate smaller, partly closed-field potentials; those are not discernible from the strong far-field potentials which originate from the supragranular activity and — especially in A 17 —from farther distant events.

Notes: Summary The distribution of the interhemispheric projection from area 17 and 18 was studied using the anterograde degeneration technique. Besides the classical visual areas (17, 18, 19), area 21 and several visual areas in the middle suprasylvian sulcus also received visual callosal input. In the four terminal areas of the middle suprasylvian sulcus the projection was found to be focused on representations of the vertical meridian including the area centralis, as in the classical visual areas. An increase of the width of visual field represented in the zone of callosal terminations can be seen from area 17 through area 18 to area 19 and possibly this trend continues in the suprasylvian visual areas.

Notes: Abstract The effects of the ergolene derivatives bromocriptine, dihydroergotoxine, methysergide, d-LSD, CF 25-397, and 29-712 on the metabolism of the biogenic amines in the brain of the rat were investigated. All six ergolene derivatives were found to increase the concentration of 4-hydroxy-3-methoxyphenylethylene glycol sulphate in the brain stem, i.e., to increase the turnover of noradrenaline (NA). Since in brain homogenates the agents inhibited the binding of 3H-dihydroergocryptine to α-adrenoceptors, but only weakly inhibited the binding of 3H-alprenolol to β-adrenoceptors, it is suggested that the increased turnover of NA may be a consequence of a blockade of α-adrenoceptors by ergolenes. All of the ergolenes increased the concentration of serotonin (5-HT) in the cortex, but only bromocriptine and 29-712 increased the concentration of 5-hydroxyindoleacetic acid (5-HIAA), the other compounds decreasing the concentration of this metabolite, i.e., inhibiting 5-HT turnover. Reserpine-induced PGO waves in the cat were inhibited by all six compounds, bromocriptine and 29-712 being the least active. Both of these findings suggest that the ergolenes possess serotonergic activity. The increase in the concentration of 5-HIAA after bromocriptine and 29-712 may be secondary to some action on other systems. The actions of the ergolenes on the metabolism of dopamine (DA) in the striatum are more complex. Bromocriptine, 29-712, and, to a much lesser extent, dihydroergotoxine reduced the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC), i.e., they inhibited DA turnover. These findings are compatible with the proposed dopaminergic activity of the drugs. CF 25-397 caused a slight increase in the DOPAC concentration at high doses, and d-LSD and methysergide caused pronounced increases. At doses below 1 mg/kg i.p., d-LSD decreased the DOPAC concentration. This biphasic effect of d-LSD may be due to interaction with different types of DA receptors or may reflect some secondary action of the compound. The profiles of activity of the various ergolenes are discussed. Bromocriptine and 29-712, wich have similar profiles of activity, can be clearly differentiated from the other ergolenes. CF 25-397 seems to be a potent and, at low doses, specific serotonergic drug.

Notes: Abstract The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam. Clobazam was half as potent as diazepam in depressing the amplitude of visual evoked potentials in the nonanaesthetized rabbit, whereas the depressing effect on spinal polysynaptic reflexes in the decerebrated cat was only 1/7–1/30 of the diazepam effect. The action of clobazam and diazepam on VEP also showed differences in time course, i.e., the peak effect of clobazam lasted from 1 to 6 h after application, whereas the effect of diazepam appeared after 10min and declined already after 1 h. Both compounds had similar effects on computer-analyzed spontaneous EEG in the rabbit (power spectrum analysis), with an increase of power in the beta-band (13–39 Hz) and a decrease in the alpha (8–13 Hz) and theta (4–8 Hz) bands.

Notes: Summary Following stereotactically performed lesions in nucleus reticularis tegmenti pontis (N.r.t.) degenerating fibers are traced to the contralateral N.r.t., to the pontine nuclei, through brachium pontis to restricted areas of the cerebellar nuclei and to most parts of the cerebellar cortex where they terminate in the granular layer. Most degenerating fragments are found in the contralateral half of the cerebellum with the greatest density in the vermal lobules VI and VIIA and in the flocculus. Following injections of HRP in the various cerebellar lobules labeled cells are mainly present within limited groups in the N.r.t.. Injections in vermal lobules VI-VIII B give rise to labeled cells within circumscribed areas in the dorsal and ventral parts throughout the rostrocaudal extent of the N.r.t.. In cases with injections in lobule IX or the ventral paraflocculus labeled cells are found ventrally in the rostral half of the N.r.t., while following injections in the vermal lobules I-V labeled cells are mainly found in the ventral and caudal part of the N.r.t.. Following injections in the intermediate and lateral parts of the anterior lobe, Crus I and II, the paramedian lobule and the dorsal paraflocculus labeled cells occur within groups in medial and lateral parts throughout the rostrocaudal extent of the N.r.t.. Following injections in the flocculus labeled cells are found in a very distinct group in the dorsal and rostral part of the N.r.t., While an injection in the nodulus (lobule X) gave rise to a smaller group of labeled neurons in the dorsolateral corner in the caudal part of the N.r.t.. Labeled cells within processus tegmentosus lateralis (p.t.l.) are only found following injections in lobules VI-VIIIA, Crus I and II and the dorsal paraflocculus. From what is known about afferents to the N.r.t., it is concluded that no cerebellar lobule gets information from one only of these sources via the N.r.t.. Visual information can probably be mediated from the superior colliculus via the N.r.t. to the flocculus and to a minor extent to the vermal lobules VI-VIII B, and from the pretectum via the N.r.t. to both vermal and lateral parts of the cerebellum.

Notes: Summary The light microscopical morphology and proteinase activities are studied during the first phases of implantation in the cat, i.e. at 12, 13 and 14 days post coitum (d.p.c.). Timed matings are used to obtain exact data on the time course of implantation events. Size and shape of the blastocysts and the topographical relationships between trophoblast, zona pellucida and endometrium are studied on cryostat sections. These observations indicate that the zona pellucida is being removed at 12 d p.c. by dissolution which starts at the abembryonic pole and lateral of the embryonic disc. Since the zona has, in spite of the considerable expansion of the blastocyst, a thickness of 8–10 μm at this stage, it must have undergone a process of swelling or material must have been added invisibly. Invasion of the trophoblast into the endometrium begins between 13 and 14 d p. c. and is fully under way at 14 d p. c. Widening of the glandular lumina in the neighborhood of the blastocysts at 12–13 d p.c. indicates an early preimplantation interaction between the blastocyst and the endometrium. Amino Acid Arylamidase (Aminopeptidase) activity is found, in histochemical tests, to be high in the trophoblast but low in the endometrium in all three investigated stages. Proteinase Activity is studied with a highly sensitive gelatin substrate film test. Moderate to medium activity is found in the trophoblast at 12–13 d p.c. Very high proteinase activity is present in the invasion zone at 14 d p.c. Experiments with a large number of specific proteinase inhibitors in vitro and preliminary investigation of pH dependence show that it is mainly due to a cathepsin-B-like endopeptidase. This enzyme can be traced to both the trophoblast and the uterine epithelium. The disintegrating zona pellucida shows, at 12 d p.c., only little gelatinolytic proteinase activity. A trypsin-like endopeptidase as described for the rabbit blastocyst could not be identified with certainty in the cat but there is some indication that it might be present at 12 d p.c. Considerable trypsin-like proteinase activity is found in scattered endometrial stroma cells at all stages. The possible physiological role of the described proteinases in implantation is discussed.

Notes: Summary The blood, yolk sac, liver, spleen, and bone marrow from 65 timed embryos of 22 cats were examined using light microscopic means in six different age categories. Nucleated primitive erythroblasts derived from the yolk sac are mature by the 19th day and represent 98% of the circulating blood cells, some of them found circulating even at birth. Definitive yolk sac erythropoiesis comprises a span of up to 30 days. On the 36th day, hematopoietic contribution drops to 15%. Neutrophils and the first thrombocytes are present on the 17th day, eosinophils and lymphocytes by the 25th day. Hepatic hematopoiesis most likely begins with definitive erythropoiesis on abouth the 20th day; granulopoiesis occurs in the liver on the 25th day. Blood forming tissue in the liver amounts to 28% which drops to 4% at birth. Splenic hematopoiesis begins on about the 36th day but contributes little to the blood. Bone marrow activity begins at mid-term and supplies about 50% of the blood cells on the 45th day. Hematocrit values increase from 22% on the 36th day to 47% at birth, thus exceeding the normal value of adult cats. The red blood cell number increases from 0.8 million/mm3 on the 25th day to 3.8 million on the 45th day and 6.3 million at birth. The total leukocyte count (880 on the 45th day and 6.480 at birth) must be calculated from the differential count of nucleated cells. Primitive erythroblasts represent the most common nucleated cells on the 25th day; on the 36th and 45th day, definitive erythroblasts predominate, but are outnumbered by leukocytes at birth. On the 36th and 45th day, lymphocytes are the predominating cell type in the white blood picture. The contribution of the hematopoietic organs to the feline prenatal blood formation is shown graphically.

Notes: Summary The Golgi architecture of the Fascia dentata and hippocampus is described in the cat. The main cell types are like those found in other species. The initial collaterals of granule cell axons were demonstrated and are commented on. The interneurons proved to be of several types and subtypes not observed in lower species. The intrinsic fibers and few of the afferents — both in the dentate fascia and in the hippocampus — are discussed.

Notes: Summary Electronmicroscope studies have been performed on the greater splanchnic nerve and the nerve to the medial head of gastrocnemius muscle of control and acrylamide poisoned cats. Degeneration of unmyelinated as well as of myelinated fibres was observed in both nerves. In cats severely poisoned with acrylamide, some very large unmyelinated axons undergoing early degeneration were seen in the splanchnic nerve. In the nerve to medial head of gastrocnemius, there was a decrease in the proportion of large diameter unmyelinated axons.

Notes: Summary An 18 month old cat had a 6 month history of abnormal high stepping gait, ataxia, muscle twitching and loss of sensory perception. The clinical course was interrupted by several episodes of temporary remission. The essential pathological features were those of a polyradiculoneuritis with segmental demyelination, focal mononuclear cell infiltration and hypertrophic onion-bulb formations. The condition is compared with chronic relapsing polyradiculoneuritis in the dog and in man.

Notes: Summary A method based on an intracerebral coordinate system and contrast ventriculography was developed for Stereotaxic surgery in the cat. The intercommissural (CA-CP) line was used as the principal reference because its length showed little variability in animals within a wide weight range. The Stereotaxic coordinates of the substantia nigra (SN) in relation to the CA-CP line and the midline were evaluated in serial sections. Stereotaxic operations with the use of ventricular radiography were performed in different parts of the SN in 18 cats. Histological verification showed that the selected target regions within the SN were very accurately reached in all animals operated with this method. The precision of the Stereotaxic method based on the intracerebral coordinate system compared to the Horsley-Clarke method is discussed.

Notes: Summary Light microscopic autoradiography and electron microscopy were used to trace the nigrothalamic projections and to study the sites of termination of this pathway in the cat. Injections of tritiated amino acids or electrolytic lesions were placed in the substantia nigra pars reticularis (SNr). An accumulation of radioactivity was found in the ventral medial nucleus and in the ventromedial part of the ventral anterior nucleus. At the ultrastructural level degenerating medium size synaptic boutons and medium size myelinated fibers were observed in these nuclei. The boutons contained clear pleomorphic vesicles and formed symmetrical type synaptic contacts with regular type dendrites and vesicle-containing dendrites. The present findings indicate that the ventral medial nucleus is the principal site of termination of nigrothalamic projections in the cat.

Notes: Abstract Complete vascular isolation of the hindlimbs was performed in vagotomized cats under Sodium Pentobarbital anesthesia. The hindlimbs were perfused at constant flow with blood kept at a constant and physiological $$P_{0_2 }$$ , $$P_{{\text{C}}0_2 }$$ , and pH values by means of a specially designed pump-oxygenator system. The animals were hyperventilated with different CO2 mixtures (0%, 5%, 7% and 10% in O2) thereby changing blood gases and pH levels in the upper body but not in the hindlimb vascular bed. At body $$P_{{\text{aC}}0_2 }$$ (mm Hg) of 13.7 ±1.0 (means±SE), 30.6±1.05, 40,4±0,9 and 58.4 ±2.9 the hindlimb perfusion pressure (mm Hg) was, respectively 124±7.6, 138±7.4, 156±11.9 and 187 ±15.1. These changes in perfusion pressure were still present after complete peripheral chemoreceptor denervation but were abolished after section of the spinal cord at the T5 level. Since hindlimb perfusion pressure fell when body $$P_{{\text{aC}}0_2 }$$ was lowered below physiological levels it is concluded that part of the neurogenic vascular tone of the hindlimbs is maintained by a CO2 mediated stimulation of supraspinal structures.

Notes: Abstract The cervical vagus nerve (VN) was electrically stimulated in Nembutal-anaesthetized cats. The responses recorded from the cerebellar surface were found in lob. V and VI in a bilateral sagittal strip perpendicular to the longitudinal axis of the folia. At a longer latency, potentials were also found in the paramedian lobule. Field potential analysis confirmed the existence of a sagittal strip in the deep parts of the lobules. The distribution of these potentials and their field potential profiles indicate that they are transmitted through the climbing fiber (CF) system. Experiments with local anaesthetics and deafferentation support our view that the potentials described in the vermis by Dell and Olson (1951) could be originated extracerebellarly. A strong parallelism was found between the amplitude of the cerebellar responses and the amplitude of the group B1 component of the vagal afferent potentials, having a conduction velocity between 4 and 20 m/s. The pathway by which the vagal afferents reach the inferior olive and the functional significance of these afferents are discussed.

Notes: Summary The presence and distribution of myocardial α-adrenoceptors in different parts of the heart of various mammalian species was investigated. For this reason experiments were performed in isolated cardiac preparations of rats, guinea pigs and cats. In order to obtain more information about the nature of the cardiac α-adrenoceptors additional experiments were undertaken at different temperatures. These studies were aimed to show whether or not a conversion of β-to α-adrenoceptors or vice versa takes place. Moreover, we analyzed the influence of hypothyroidism on the sensitivity of α- and β-adrenoceptors of preparations from rats fed with propylthiouracil. Finally, we tried to find out whether stimulation of these α-adrenoceptors leads to the formation of the cyclic nucleotides cAMP and cGMP. The following results were obtained: 1. In right ventricular strips of rats, guinea pigs and cats phenylephrine stimulated α-adrenoceptors. After blockade of β-adrenoceptors the respective pD2-values of phenylephrine were 5.32, 5.99 and 5.33. The doseresponse curves obtained in the presence of α-adrenolytic drugs were shifted to the right without depression of the maximum. In the rat, in addition, the pA2-values for the α-adrenolytic drugs yohimbine (5.79) and phentolamine (7.85) were determined. They were at least 0.5 log units higher than those found in the rat for other α-adrenoceptors (Van Rossum, 1965) thus supporting the view that the population of cardiac α-adrenoceptors is different from that of other organs. In left ventricular strips of guinea pigs the pD2-value for the α-mimetic effect of phenylephrine was of the same order of magnitude as that obtained in the right ventricle. 2. In the papillary muscle of the right ventricle of guinea pigs and cats phenylephrine stimulated α-adrenoceptors. 3. In the left atrium of the rat, phenylephrine stimulated myocardial α-adrenoceptors (pD2: 5.58). Also in this preparation the pA2-values for yohimbine (6.36) and phentolamine (8.21) were different from those found for other α-adrenoceptors in the rat (Van Rossum, 1965). Likewise in strips from the left atrium of the cat myocardial α-adrenoceptors are present. 4. In spontaneously beating right atria of the rat a clear-cut positive chronotropic effect mediated by stimulation of α-adrenoceptors could not be demonstrated although in 6 out of 15 preparations a small positive chronotropic effect became evident. No positive chronotropic effect at all was obtained by stimulation of α-adrenoceptors in the cat right atrium. 5. In ventricular strips as well as in left atria from hypothyroid rats the pD2-value for the α-effect of phenylephrine was increased, in the atrium more than in the ventricle, while the pA2-values for yohimbine and phentolamine were not significantly different from the controls. Under these conditions a distinct positive chronotropic effect mediated by stimulation of α-receptors was found in the spontaneously beating rat atrium. 6. After stimulation of α-adrenoceptors in atria and ventricular strips of normal and propylthiouraciltreated rats, as well as in strips of guinea-pig ventricles or cat atria no elevation of cAMP and cGMP was observed. 7. The concept of a single adrenoceptor convertible from α- to β-type or vice versa was not supported by our experiments. These were carried out at different temperatures on left atria and on ventricular strips of rat hearts using the irreversible α-adrenoceptor blocking agent phenoxybenzamine. 8. The present experiments provide evidence for the existence of α-adrenoceptors in the myocardium of various mammalian species. Their stimulation produces positive inotropic effects without increases in heart rate.

Notes: Summary Gene frequency surveys conducted in Alexandria and Cairo reveal genetic profiles which are extensions of those that characterize the cat populations of European cities. For nine selected comparisons with Alexandria, regression analysis indicates that a linear function best describes the relationship between Nei's and Cavalli-Sforza's genetic distance indices and geographic distance.

Notes: 5,6-Dimethylidene-exo-2,3-epoxynorbornane (1) is reduced slowly by LiAlH4 in boiling tetrahydrofuran (THF) and furnishes a mixture of 5,6-dimethylidene-exo-2-norbornanol (2), 2,3-dimethylidene-anti-7-norbornanol (3) and principally 6-methyl-5-methylidene-anti-3-nortricyclanol (4). The yield of 4 is the highest for low initial concentrations of LiAlH4; it decreases in favour of alcohols 2 and 3 at high concentration of LiAlH4. The reduction of 1 with AlH3 in THF yields 3 as the major product, thus revealing an efficient synthesis of 7-substituted-2, 3-dimethyl-idenenorbornane derivatives. No alcohol 2could be isolated by LiEt3BH reduction of 1. LiAlD4 reduces 1 into the monodeuterated alcohols 2-d, 3-d and 4-d. The deuterium label is found in the endo-position at C (3) in 2-d, in the exo-position at C(5) in 3-d and in the methyl group of the tricyclic alcohol 4-d. Mechanistic limits for the formation of 2, 3 and 4 are discussed briefly.

Notes: The enthalpy of formation of tris(methylidene)-cyclopropane (“[3]radialene”, 1) has been determined as ΔHfO = 396 ± 12 kJ mol-1 from three fragmentation reactions of its molecular ion 1+ formed from 1 by photoionisation using synchrotron radiation. Comparative electron impact measurements using conventional mass spectrometry were also performed. A treatment of the latter data is described which leads to satisfactory agreement with the photoionization data. The experimental value of ΔHfO(1) is compared with various theoretical estimates. The strain energy of 1 is calculated to be 226.3 kJ mol-1. Linear extrapolation of this quantity from the increase of strain in passing from cyclopropane to methylidenecyclopropane yields 282.4 kJ mol-1. The discrepancy between these values, already predicted by Dewar and Baird ten years ago from theoretical calculations, is discussed on the basis of maximum overlap considerations. The enthalpy of formation of bis(methylidene)cyclopropane is predicted to be ΔHfO= 309 kJ mol-1.

Notes: Leaf-gland Pigments: 6-Novel p-Quinomethanes of the Abietane Series from Plectranthus parviflorus WILLDThe above mentioned plant accumulates in its red coloured leaf-glands a complex mixture of strongly dehydrogenated abietanols. They were separated (with difficulties) to yield 6 novel compounds. Spectroscopic and chiroptic data show them to be esters of either 11, 19-dihydroxy- or 2 α, 11-dihydroxy-abieta-5, 7, 9 (11), 13-tetraen-12-one 2a and 3a, respectively. Specifically, the 19-O-p-hydroxybenzoate (2d) parvifloron C, the 19-O-vanilloate (2c) parvifloron B, the 19-O-p-hydroxy-benzoate (2d) parvifloron C, the 19-O-3′,4′-dihydroxybenzoate (2e) parvifloron E, the 2 α-O-p-hydroxybenzoate (3b) parvifloron D, and the 2 α-O-3′,4′-dihydroxy-benzoate (3c) parvifloron F. Reduction by LiAlH4 splits the ester function and reduces the p-quinomethane to a colourless pyrocatechol derivative which, by air oxidation, regenerates the red p-quinomethane system of 2a and 3a.

Notes: A calculation of the modification of the optical absorptions of an isotropic sample by a uniform external electric field is presented. The induced orientational anisotropy, the Stark shift and the field. dependence of the transition moment are taken into account up to the second order in the field. The final expressions differ in the contributions from the transition polarizabilities from previous results.

Notes: The photoelectron spectrum of tris (methylidene)-cyclopropane 1 (“[3]radialene”) is reported and the electronic states of 1+ assigned. Jahn-teller activity in the degenerate states of 1+is discussed. Differences in the Franck-Condon profile of the first PE band and the Rydberg series in the Vacuum-UV./UV. absorption spectrum indicate for the Rydberg series (n=3) a 1A″2-species, which supports earlier tentative proposals. The high intensity absorption in the 5.5 eV-6 eV energy range of the latter spectrum recorded earlier are definitely due to impurities. The vibrational fine structure of a weak band system around 5.5 eV in our spectrum suggests for this transition S0→S2(1A′1), which is dipole forbidden but borrows intensity from S1(1E′) trough vibronic coupling via an e′-mode. From vapor pressure measurements ε(λmax=289 nm) = 9390± 1170 for gaseous 1 was found.

Notes: IR. and Raman spectra of LnONO3 (50-4,000 cm-1, Ln=La, Gd, Eu, and Dy) are reported and discussed. The low frequency region of the spectra reflects the cubic structure of these compounds. The dimensions of the cubic unit cells determined by X-Ray powder diagrams are: 12.81 ± 0.05 Å for EuONO3, 12.69 ± 0.05 Å for GdONO3, and 12.67 ± 0.05 Å for DyONO3. The vibrational frequencies of the nitrato group are consistent with a bidentate nitrate of C2v symmetry. The synthesis of anhydrous Ln (NO3)3 (Ln=La, Gd, Eu, and Dy) by dehydration of the corresponding penta- or hexahydrates is described. The IR. and Raman spectra (50-4,000 cm-1) are analysed. Splitting of the bands point to a complex structure of these compounds. All six vibrational modes of the nitrato group are observed and the data are again consistent with bidentate NO-3 moieties. Finally, an analytical control of the purity of Ln (NO3)3 is suggested.

Notes: Synthesis of 3-Dimethylamino-3a,4,5, 7a-tetrahydro-1H-isoindol-1-ones by Intramolecular Diels-Alder ReactionThermolysis of N2-acylamidines, the acyl group of which derives from an α,β,γ,δ-unsaturated carboxylic acid (2, 5-7), yields 3-dimethylamino-3a,4,5,7a-tetrahydro-1H-isoindol-1-ones (3,8-10, Schemes 1 and 3) in 63-78%. Only the thermodynamically controlled cis-fused ring system is formed. The starting materials are readily available by the reaction of 3-dimethylamino2H-azirines (1 and 4) and carboxylic acid chlorides.

Notes: Reactions of Aziridino-nitrenes: Synthesis of Polycyclic Bisaziridines and 1,2-Bisaziridino-diazenesVorgetragen in der Versammlung der Schweizerischen Chemischen Gesellschaft in Bern am 7.Oktober 1977.7-Amino-7-azabicyclo[4.1.0]-3-heptene (11b), cis-9-amino-9-azabicyclo[6.1.0]-nonane (12b), cis-9-amino-9-azabicyclo[6.1.0]-(4Z)-nonene (13b), as well as exo- and endo-3-amino-3-azatricyclo[3.2.1.02,4]-6-octene (14b and 15b) were synthesized by addition of oxidatively generated phthalimido-nitrene (6) to 1,4-hexadiene, (Z)-cyclooctene, (1Z,5Z)-cyclooctadiene, and bicyclo[2.2.1]heptadiene, respectively, followed by hydrazinolysis of the corresponding N-phthalimido-aziridines 11a-15a.Lead tetraacetate oxidation of the two unsaturated N-amino-aziridines 11b and 15b at -70° yielded diazapolycyclic structures by intramolecular addition of the intermediate aziridino-nitrenes 11c and 15c to the δ, ε-situated C, C-double bond; the products obtained in good yields were 1,5-diazatetracyclo [3.3.0.02,8. O4,6]-octane (16) and 3,7-diazapentacyclo [3.3.1.02,4.03,7.06.8] nonane (17), respectively Oxydation of the unsaturated N-amino-aziridine 13b under the same conditions did not cause intramolecular addition of the nitrene 13c to the ε, ζ-situated C, C-double bond; instead 1,2-bis (cis-9-azabicyclo [6.1.0]-(4Z)-nonen-9-yl)-diazene (20) was obtained in low yield and (1Z, 5Z)-cyclooctadiene as the main product. Both products can be rationalized as derived from the intermediate nitrene 13c with 13b and the olefine as the result of a fragmentation of 13c under extrusion of N2. As. expected, oxidation of the saturated N-amino-aziridine 12b led to the 1,2-bisaziridino-diazene 21 and (Z)-cyclooctene in a ratio of 4:6. Surprisingly, oxidation of 7-amino-7-azabicyclo [4.1.0]-heptane (10b) produced only fragmentation of the corresponding nitrene 10c to cyclohexene. Finally, oxidation of the exo-N-amino-aziridine 14b yielded a complex not yet resolved product mixture in low overall yield. Attempts to add the oxidatively generated aziridino-nitrene 12c to cyclohexene, methyl acrylate, and dimethylsulfoxide were without success.Heating the 1,2-bisaziridino-diazenes 20 and 21 at their respective m.p. temperatures caused thermal fragmentation to occur with evolution of nitrogen. The bisaziridines 26 and 28 as well as the aziridines 27 and 29, respectively, were isolated. These products could be the result of a radical pathway, whereas a small amount of (Z)-cyclooctene, also generated in the thermolysis of 21, might be formed by a competing cheletropic pathway.The 1H-NMR-spectra of the derivatives of cis-9-azabicyclo[6.1.0]nonane, namely of 12a, 12b, 21, 28 and 29, showed signals for some of the aliphatic protons which were separated from the others at relatively low field (around 2.5-1.8 ppm). These signals accounted for 4 (with 12b for 2) protons in each of the cis-9-azabicyclo[6.1.0]nonane subunits, i.e. more than the 2 expected for the aziridine methine protons. The additional signals must be assigned to methylene protons (2 or even 4 of them) probably situated on the other side of the eight membered ring and deshielded by the motion-average proximity to the aziridine nitrogen atom.

Notes: On the Carotenoids Flavoxanthin and Chrysanthemaxanthin: 1H-NMR., 13C-NMR. and Mass Spectra, Absolute Configuration, Survey of Published DataVery pure flavoxanthin (1) and chrysanthemaxanthin (2) have been reisolated from flower heads of Taraxacum officinale. Both compounds were characterized by chromatographic, chemical and chiroptical data and extensive NMR. measurements. Examination of many published data on 1 and 2 led to the conclusion that flavoxanthin has often been mistaken for chrysanthemaxanthin and vice versa.Chemical degradation of 1 and 2 to (-)-loliolide (5) coupled with NMR. evidence (ASIS, spin-decoupling, NOE) allowed the assignment of the absolute configurations of 1 and 2. Thus (+)-flavoxanthin is (3S,5R,8R, 3′R,6′R)-5, 8-epoxy-5, 8-dihydro-β, ε-carotene-3, 3′-diol and (+)-chrysanthemaxanthin its C(8)-epimer.

Notes: Synthesis and Chirality of (5S,6R)-5,6-Epoxy-5,6-dihydro-β,β-carotene and (5R,6R)-5,6-Dihydro-β,β-carotene-5,6-diol, a Compound with Unexpected Solubility CharacteristicsWittig-condensation of azafrinal (1e) with the phosphorane derived from 7 leads to a (1:3)-mixture of (E)-9′- and (Z)-9′-β,β-carotene-diol 3, from which pure and optically active 3 ((5R,6R)-5,6-dihydro-β,β-carotene-5,6-diol) has been isolated as bright violet leaflets, m.p. 168°. Due to the trans-configuration of the diol moiety and to severe steric hindrance, hydrogen bonding is reduced to such an extent, that 3 behaves much more as a hydrocarbon than as a diol. There is good evidence that the so-called ‘β-oxycarotin’ obtained by Kuhn & Brockmann [15] by chromic acid oxidation of β, β-carotene is the corresponding racemic cis-diol. 3 has been converted into (5S, 6R)-5,6-epoxy-5.6-dihydro-β,β-carotene (4), m.p. 156°. This transformation establishes for the first time the chirality of a caroteneepoxide (without other O-functions).Full spectral and chiroptical data including a complete assignement of 13C-chemical shifts for azafrin methyl ester and 3 are presented.

Notes: As an extension of previous studies on the total synthesis of (2R,4′R,8′R)-α-tocopherol (1) [1] [2], (S)-(-)-2-(6-benzyloxy-2,5,7,8-tetramethylchroman)acetic acid (6), a pivotal intermediate, possessing the absolute configuration required for construction of 1 was prepared by optical resolution of the racemic modification 11. the latter substance was obtained by two routes, one emanating from the hydroxy acetal 7 [1] and the other based upon the Lewis acid mediated cycloaddition of trimethylhydroquinone to rac.-3-hydroxy-3-methylpent-4-en-l-yl acetate (16) giving rac. ethyl 2-(6-hydroxy-2,5,7,8-tetramethyl-chroman)acetate (12).

Notes: Thermodynamic study of charge transfert complexes (n-σ*) in solutionCharge transfer complexes of quinoline and substituted quinolines (donors) with iodine, iodine chloride, and iodine bromide (acceptors) have been studied spectrophotometrically in CCl4. The 1:1 stoechiometry of these complexes was verified by means of the continous variations method and the appearance of isosbestic points. Simultaneous determination of the equilibrium constant and enthalpy of adduct formation was carried out by calorimetry.It was observed for every donor that the equilibrium constants of the complexes studied increase with the strength of the acceptors. A linear correlation between enthalpy of adduct formation and donor strength was obtained only for the complexes Donor ICI.

Notes: Syntheses of jasmone (1), methyl jasmonate (3) and γ-jasmolactone (2) are reported, (Z)-nona-1, 6-dien-3-one (4) serving as common intermediate.

Notes: The Conversion of Eperuic Acid into Ethers of the enantio-14, 15-Dinorlabdane Series5 and 6 are strongly odiferous substances of the ambra-type. Their enantiomers 7 and 8, hitherto unknown, have been synthesized from eperuic acid (4) and their olfactory properties compared with those of 5 and 6. 4 was esterified by CH2N2 and dehydrogenated with (C6H5Se)2/H2O2 to the α,β-unsaturated ester 9 (61%). Oxidation by KMnO4 in acetone yielded the ketone 3 (60%). Epoxidation followed by treatment with acid converted 3 into the acetals 7 (61%) and 8 (14%). 7 and 8 differ from 5 and 6 in odor intensity, and 6 and 8 show slightly different odor quality.

Notes: The natural products methyl dehydrojasmonate (1) and tuberolactone (2) have been synthesized from methyl jasmonate (3) and jasmolactone (4) resp., via sulfenylation-sulfoxide pyrolysis.

Notes: Comparative investigation of reactivities and ion structures upon electron impact induced degradations of the isomeric hydroxy cinnamic acid methyl estersBy analysis of energy release data in metastable peaks it is shown that m- and p-hydroxy cinnamic acid methylesters retain specific structural features upon degradation under electron impact, although their spectra are very similar and the shapes of the metastable peaks due to the initial methoxy cleavage are identical. A pronounced charge radical localization in the molecular ion is indicated. The o-isomer is found to yield a coumarin type structure by elimination of methanol, whose further degradation by decarbonylation involves at least three different mechanisms. The resulting ion structures are different from benzofuran.

Notes: 2-Thiopyridone (2-mercaptopyridine, 1) was found to be a very suitable reagent for removing the Nα-o-nitrophenylsulfenyl (NPS-) group in both conventional and solid-support peptide synthesis. A 3- to 5-molar excess of the reagent together with an equivalent amount of glacial acetic acid in methanol, dimethylformamide, or methylene chloride produces the soluble, stable mixed disulfide, 2-nitrophenyl 2-pyridyl disulfide (2), and the Nα-deprotected amino-acid or peptide. The yields are quantitative in less than 5 min if all educts are dissolved, in about 20 to 30 min in solid-support synthesis. No modifications of either the indole side-chain of tryptophan or of a series of side-chain protecting groups, in particular of the t-butyl type, are produced. No adverse side-reactions (insoluble disulfides) were observed. The procedure is illustrated with a series of amino-acid derivatives and with the solid-support synthesis of [5-leucine]-enkephalin.

Notes: The two novel tricyclic C10H16 compounds anti- and syn-tricyclo [4.2.1.12,5]- decane (16 and 17, respectively) were synthesized starting either from the photodimer 2 (anti) or the two cycloaddition products 8 (anti) and 9 (syn).

Notes: The title condensations gave respectively: gem-bisarylated cyclic amines 3a-k or monoarylated unsaturated cyclic amines 4a-g, 1,3-bisarylated cyclohexadienes 6a, 6b, the condensed bicyclo [2,2,2]-octane 8. In addition the aromatic ketone 9 gave the fluorenone 10 on treatment with polyphosphoric acid (PPA).

Notes: Nickel-catalysed Synthesis of α-NornicotinesSchiff's bases 1 and butadiene generally co-oligomerize on nickel catalysts to yield octatrienyl-substituted amines 2 and octadienyl-substituted imines 3.Schiff's bases 4 and 5, on the other hand, react with 1, 3-dienes to give new [3+2]-cycloadducts 6. In addition to the appropriately functionalized α-nornicotine derivatives some higher oligomers are formed.

Notes: The ligands (L) bis (2-pyridyl) methane (BPM) and 6-methyl-bis (2-pyridyl)methane (MBPM) form the three complexes CuL2+, CuL22+, and Cu2L2H-22+ with Cu2+. Stability constants are log K1 = 6.23 ± 0.06, log K2 = 4.83 ± 0.01, and log K (Cu2L2H-22+ + 2H2+ ⇌ 2 CuL2+) = -10.99 ± 0.03 for BPM and 4.56 ± 0.02, 2.64 ± 0.02, and -11.17 ± 0.03 for MBPM, respectively. In the presence of catalytic amounts of Cu2+, the ligands are oxygenated to the corresponding ketones at room temperature and neutral pH.With BPM and 2,4,6-trimethylpyridine (TMP) as the substrate and the buffer base, respectively, the kinetics of the oxygenation can be described by the rate law \documentclass{article}\pagestyle{empty}\begin{document}$${{ - {\rm d}\left[{{\rm O}_2 } \right]} \mathord{\left/ {\vphantom {{ - {\rm d}\left[{{\rm O}_2 } \right]} {{\rm dt}}}} \right. \kern-\nulldelimiterspace} {{\rm dt}}} = {{k_1 \left[{{\rm CuL}_2^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_1 \left[{{\rm CuL}_2^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}} + k_2 \left[{{\rm CuL}_2^{2 + } } \right]\left[{{\rm TMP}} \right] + {{k_3 \left[{{\rm CuL}^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_3 \left[{{\rm CuL}^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}} + {{k_4 \left[{{\rm Cu}_2 {\rm L}_2 {\rm H}_{ - 2}^{2 + } } \right]} \mathord{\left/ {\vphantom {{k_4 \left[{{\rm Cu}_2 {\rm L}_2 {\rm H}_{ - 2}^{2 + } } \right]} {\left[{{\rm H}^ + } \right]}}} \right. \kern-\nulldelimiterspace} {\left[{{\rm H}^ + } \right]}}$$\end{document} with k1 = (5.9 ± 0.2) · 10-13 mol l-1 s-1, k2 = (4.0 ± 0.6) · 10-4 mol-1 ls-1, k3 = (1.1 ± 0.1) · 10-12 mol l-1 s-1, and k4 = (9 ± 2) · 10-14 mol l-1 s-1.

Notes: Nickel-catalysed Isomerization of Unsaturated AzocompoundsUnsaturated azocompounds, produced by the nickel-catalysed reaction of butadiene with hydrazones, can be isomerized in presence of the same nickel catalyst. The influence of nickel concentration, temperature and structure of the azocompound on this rearrangement is described.

Notes: Nickel-catalysed Reaction of 2-Aza-1, 3-butadienes with 1, 3-ButadieneThe nickel-catalysed reaction of butadiene with 2-azabutadienes yields a mixture of 1 aza-1,5,9-cyclododecatrienes, N-alkylidene-divinylcyclohexylamines and open chained 2:1 adducts.

Notes: The preparation of the vitispiranes 9 and 10, identified among the volatiles of vanilla, from the theaspiranes 1 and 2 via the intermediates 4 and 5 and the allyl alcohols 7 and 8, respectively, is described. The theaspiranes 1 and 2 can be obtained from the compounds 11-15 or 24-26.

Notes: The binding of various flavins by apoflavodoxins from P. elsdenii and A. vinelandii has been studied by the temperature-jump technique using fluorescence detection. P. elsdenii apoflavodoxin interacts only with flavins possessing 5 carbon atoms in the N(10) side chain and a terminal phosphate group. Employing a wide range of concentrations of deoxy-FMNFlavin = 3,4-dimethyl-lO-substituted isoalloxazine = 3,4-dimethyl- lO-substituted-2,3,4,10-tetrahydro-benzo[g]-pteridine-2,4-dione; FMN = riboflavin-5′-monophosphate. and apoflavodoxin only one relaxation process was observed, indicating a one-step binding mechanism. With native flavodoxin no relaxation could be observed.The kinetic parameters of the interaction of A. vinelandii apoflavodoxin with various flavin analogs (Structure I) have also been investigated. The interaction between apoflavodoxin and flavin derivatives carrying an ionizable, terminal functional group on the side chain becomes very weak when the number of the side chain carbon atoms is decreased below 4. This observation is interpreted in terms of repulsive forces due to negatively charged amino acid residues located in the flavin side chain binding region of the apoflavodoxin. All complexes studied revealed only one relaxation process. This observation is in contradiction with published results [10]. The published traces are instrumental artifacts.

Notes: A short synthesis of 3,5-dimethyl-1,2,4-trithiolane (1), a well-known constituent of processed meat, is described.

Notes: In the presence of Ni2+ the template reaction between 2,6-diacetylpyridine and 4-(2-dimethylaminoethyl)- or 4-(2-hydroxyethyl)-1, 7-diamino-4-azaheptane yields the complexes of either the open-chain ligand (3 and 11) or of the macrocycle (4 and 12). Reduction of the imino group in 4 and 12 with PtO2/H2 gives 5 and 13, respectively. In the case of the dimethylamino derivative 5 a mixture of at least four isomers was obtained. These were partially separated by chromatography on Sephadex SP-25 cation exchanger. Through demetalation of the Ni2+ complexes by cyanide the new macrocycles 7 and 14 were isolated, from which the corresponding Zn2+ and Cu2+ complexes were prepared.The macrocyclic Ni2+-complexes 4, 12, 5 and 13 can exist in two forms depending on the pH of the solution. At low pH protonation of the dimethylamino or hydroxy group in the side chain occurs. The metal ion is then bound to the four nitrogen atoms of the macrocycle in a square planar ligand field. At higher pH, however, the dimethylamino or hydroxy group (the last one also in its deprotonated form) can coordinate to one of the axial positions, whereby pseudooctahedral coordination geometry is induced. This reaction can be quantitatively described by a reversible acid-base equilibrium, the pKH of which greatly depends on the nature of the functional group, the degree of unsaturation of the macrocycle and the metal ion.The acid-base reaction and the concomitant structural change are a direct consequence of the unique combination of the rigid and kinetically stable structure of the macrocycle and of the flexible and kinetically labile functional group of the side chain.

Notes: The He (Iα) photoelectron spectra of the four unsaturated oxides 3,4-dihydropyran (6), γ-pyran (7), 2, 3-dihydro-1, 4-dioxin (9) and 1, 4-dioxin (10) are reported and analysed. Band assignments are based on ab-initio calculations, using the STO-3G basis set. The proposed orbital sequences (with reference to the coordinate systems given in Table 1) are, for the top three orbitals: 6, π, nσ, nπ; 7, 3b1(π), 1a2(π), 11a1(σ); 9, 11b(π), 12a(σ), 11a(π); 10, 2b3u(π), 1b1g(π), 6ag(σ). Finally the (almost) localized π-orbitals have been computed by the Foster-Boys localization procedure.

Notes: The spiro-lactone 3 was obtained by N-bromosuccinimide (NBS) oxidation of the carboxylate 2 at - 20°. When 2 was oxidized at 10° the spiro-lactone 4 was the main product. Compound 4 was rearranged with triethylamine to the spiro-lactone 9 whereas the stereoisomeric spiro-lactones 14 and 15 were obtained by NBS oxidation of the carboxylate 13. The ketones 3, 4, 9, 14 and 15 were reduced with NaBH4 to the corresponding alcohols 5, 6, 10, 16 and 18 respectively; these were hydrogenated to the alcohols 7, 8, 11 and 20. The allylic alcohols 5 and 6 gave the benzochromanone 1 when heated in polyphosphoric acid whereas the benzochromanones 12 and 21 were obtained from the alcohols 10 and 16 respectively.

Notes: The Reaction of Phenols with N-substituted MaleinimidesPhenoxysuccinimides are formed by the base catalysed addition of phenols to N-substituted maleinimides. In the presence of catalytic amounts of tertiary aliphatic amines yields as high as 90% are obtained. A series of adducts of mono-and di-phenols to mono- and bismaleinimides is described. Pure phenoxysuccinimides are stable compounds but the basic catalysts of their formation give rise to their decomposition into the phenolic component and oligomeric maleinimide. A nucleophilic reaction mechanism both for the formation and the decomposition is discussed. A new crosslinked addition polymer from a diphenol and a bismaleinimide with a surprisingly high heat stability is described.

Notes: Macrocyclic and noncyclic neutral ionophores. Effect of the macrocyclic ring on the ion selectivityA series of macrocyclic 3, 6-dioxaoctanedioic diamides was prepared. Their ion selectivity in membranes was compared with nonmacrocyclic analogues. The ion selectivity as well as the capability to extract ions from aqueous solutions to an organic phase decreases with decreasing ring size.

Notes: Structure and properties of 5-epi-flavoxanthin and 5-epi-chrysanthemaxanthinThe absolute configurations of 5-epi-flavoxanthin (6) and 5-epi-chrysanthemaxanthin (7) prepared by acid catalysed rearrangement of semi-synthetic lutein epoxide 5 are shown to be (3S, 5S, 8R, 3′R, 6′R) and (3S, 5S, 8S, 3′R, 6′R), respectively. Contrary to published data [5] the relationship of the polyene chain and H3(18) on the dihydrofurane ring is cis for the pair of stereoisomers having a Δδ = δ (H—C(7)) - δ (H—C(8)) = 0,22 ppm and 3J ≡ 0. These conclusions are in full accord with the chiroptical data.

Notes: Influence of the lipophilicity of 3,6-dioxaoctanedioic diamides on their ion carrier propertiesA series of lipophilic 3,6-dioxaoctanedioic diamides (potential ionophores for Ca2+) have been prepared. With increasing lipophilicity the ionophoric behavior of these ligands vanishes. This loss is shown to be due to kinetic limitations in the exchange reactions between aqueous phase and membrane phase.

Notes: Oscillating Chemical Reactions. 11. Behaviour of the “induction period” in the BrO3-/Ce4+/Cyclohexanon and BrO3-/Ce4+/Cyclopentanon systems(1)The addition of α-monobromoketone, one of the products of reaction of the BrO3-/Ce4+/Cyclohexanon (S1) and BrO3-/Ce4+/Cyclopentanon (S2) oscillating systems, decreases and even suppresses the induction period (τind.) in the case of S2.Such is not the case with S1: τind. increases and the oscillations can even be completely inhibited.(2)The order of addition of the reagents and the time lapse (tadj.) preceding the addition of the last of them influences τind., particularly when the last reagent added is Ce4+.(3)In our experimental conditions, the inhibition of the oscillatory phenomenon by Cl- ions is definite only for | Cl- | ≥ 5,0 · 10-2M (S1) and |Cl-| 〉 2,5 · 10-3M (S2); for lower concentrations τind. increases with | Cl-|.

Notes: Preparation of Cortexon-Analogs with Conformatively Fixed Side ChainThe synthesis of cortexon-analogs with a conformatively fixed side chain is described. The key step in the synthesis consists of an intramolecular displacement of bromine in position 21 by the oxygen of a 17α-hydroxymethyl group.

Notes: Allyl sulfides and a selenide are metallated and silylated with chloro (penta-methyl)disilane. Treatment of the resulting disilanylmethyl sulfides 4 with trimethyloxonium tetrafluoroborate furnishes 1,1-disilyl-2-alkenes 5 in good yields. Some synthetic possibilities of 5 are outlined.

Notes: Starting from 5-chloro-2-pentanone (1) the naturally occurring 10-membered lactone phoracantholide J (8a) has been synthesized as its racemate in a sequence of six steps (Scheme 2). Salient features of the syntheis include an internal selenium assisted acetal formation (4→5) and a stereoselective Claisen rearrangement (6→7→8). This general synthetic strategy offers an alternative approach towards the construction of macrocyclic lactones.

Notes: The conversion of α-hydroxythioacetals to ketene thioacetals possessing an unprotected carbonyl function is described. Besides the intrinsic utility of this transformation it is of interest to recognize that ketene thioacetals are protected carboxyl groups.

Notes: During the reaction of allyl ethers, allyl sulfides and allyl selenides with in situ prepared dichloroketene (1), 2 competing pathways are observed. Besides [2+2]-cycloaddition, an unprecedented [3,3]-sigmatropic (Claisen) rearrangement via a 1,3-dipolar intermediate takes place. It leads to O-, S- or Se-esters of α,α-dichloro-γ, δ-unsaturated acids containing an inverted allylic group. Starting from cyclic n-membered α-vinyl-substituted ethers, lactones with n+4-membered rings are formed. A very facile synthesis of the naturally occurring macrolides (±)-phoracantholide I (10) and (±)-phoracantholide J (11) illustrates the synthetic utility of this new ‘ketene’ Claisen rearrangement.

Notes: Syntheses of Sulfonated Derivatives of 4-Amino-1, 3-dimethylbenzene and 2-Amino-1, 3-dimethylbenzeneDirect sulfonation of 4-amino-1, 3-dimethylbenzene (1) and sulfonation of 4-nitro-1,3-dimethylbenzene (4) to 4-nitro-1,3-dimethylbenzene-6-sulfonic acid (3) followed by reduction yield 4-amino-1,3-dimethylbenzene-6-sulfonic acid (2). The isomeric 5-sulfonic acid (5) however is prepared solely by baking the acid sulfate salt of 1. Reaction of sulfur dioxide with the diazonium chloride derived from 2-amino-4-nitro-1,3-dimethylbenzene (7) leads to 4-nitro-1,3-dimethylbenzene-2-sulfonyl chloride (8), which is successively hydrolyzed to 4-nitro-1,3-dimethylbenzene-2-sulfonic acid (9) and reduced to 4-amino-1, 3-dimethylbenzene-2-sulfonic acid (6). Treatment of 4-amino-6-bromo-1,3-dimethylbenzene (12) and 4-amino-6-chloro-1, 3-dimethylbenzene (13), the former obtained by reduction of 4-chloro-6-nitro-1,3-dimethyl-benzene (10) and the latter from 4-chloro-6-nitro-1, 3-dimethylbenzene (11), with oleum yield 4-amino-6-bromo-1,3-dimethylbenzene-2-sulfonic acid (14) and 4-amino-6-chloro-1,3-dimethylbenzene-2-sulfonic acid (15) respectively; subsequent carbon-halogen hydrogenolyses of 14 and 15 lead also to 6 (Scheme 1).Baking the acid sulfate salt of 2-amino-1, 3-dimethylbenzene (17) gives 2-amino-1, 3-dimethylbenzene-5-sulfonic acid (16), whereas the isomeric 4-sulfonic acid (18) can be prepared by either of the following three possible pathways: Sulfonation of 2-nitro-1,3-dimethylbenzene (20) to 2-nitro-1,3-dimethylbenzene-4-sulfonic acid (21) followed by reduction or sulfonation of 2-acetylamino-1,3-dimethylbenzene (19) to 2-acetylamino-1,3-dimethylbenzene-4-sulfonic acid (22) with subsequent hydrolysis or direct sulfonation of 17. Further sulfonation of 18 yields 2-amino 1,3-dimethylbenzene-4,6-disulfonic acid (23), the structure of which is independently confirmed by reduction of unequivocally prepared 2-nitro- 1,:3-dimethylbenzene-4,6-disulfonic acid (24)(Scheme 2).

Notes: Absolute configuration of the 3,5-diaminohexanoic acid produced in the β-lysine mutase reactionThe (3S, 5S)-configuration of the 3,5-diaminohexanoic acid 3 produced by the coenzyme-B12-dependent β-lysine mutase from Clostridium sticklandii has been determined by two different methods: by comparison of the 1H-NMR.-spectrum of its δ-lactam with that of synthetic (±)-cis-and (±)-trans-4-amino-6-methyl-piperidones (1 and 2) and by chemical correlation with (+)-(6S)-6-methyl-piperidone-2 (9).

Notes: A (3-mercapto-1-succinyl)-TMV ∊-maleimidohexanoyl-[1-asparagine, 5-valine]-angiotensin II conjugate was prepared and used for cooperative affinity labeling of bovine adrenal cortex cell membrane vesicles containing angiotensin-binding sites. The labeling was demonstrated by electron microscopy and by CsCl and sucrose density gradient centrifugation Preliminary evidence for specific binding and for the postulated cooperative affinity interaction is produced.

Notes: The stereochemistry of trans- and cis-2, 4-dimethyl-tetrahydroquinolines, 6 and 7 were derived from 1H-NMR. studies. These were converted respectively into trans- and cis-5, 6-dihydro-4, 6-dimethyl-4H, 8H-pyrido [3, 2, 1-de]phenanthridin-8-ones 18 and 20 by a Pschorr reaction on the anthranilamides 10 and 15. Bromophenanthridones 19 and 21 were similarly prepared from bromoanthranilamides 12 and 17. Detailed 1H-NMR. studies on 18 and 20 indicated axial disposition of the methyl groups at C(2) in both compounds in contrast to the situation in 6 and 7. This is presumably to avoid adverse CH3CO group interaction of the A (1, 3) type. The severity of this is gauged by the preference of 20 for a normally forbidding 1, 3-diaxial orientation of two methyl groups. X-ray crystallographic studies on 19 and 20 confirm the stereochemical assignments.

Notes: The use of tobacco mosaic virus (TMV) covalently loaded with hormones or other small molecules for various purposes including receptor detection and isolation is proposed. The basic principle is that of cooperative affinity interactions involving (large) numbers of artificially introduced sites (e.g. hormones) of the modified virus on the one hand and membrane-bound sites (e.g. receptors) of a cell or of a cellmembrane particle on the other. In order to test the feasibility of such TMV/hormone conjugates, TMV carrying about 500 molecules of a biologically active α-melanotropin analogue was synthesized, and characterized by its aspect under the electron microscope, by its infectivity, its melanophore-stimulating activity, and its reaction with antisera against α-melanotropin. The observed hormonal activity is in accordance with the idea of cooperative affinity interactions.

Notes: 5, 7-Dihydroxy-8-methoxy-chroman-4-one from the Bulb Wax of Eucomis comosaFrom the bulb wax of Eucomis comosa (HOUTT.) WEHRH. (Liliaceae) 5, 7-dihydroxy-8-methoxy-chroman-4-one (1) was isolated. The structure was confirmed by direct comparison with a synthetic specimen. 1 is the first natural chroman-4-one which is unsubstituted in the heterocyclic ring.

Notes: Several long chain primary alcohols (saturated, monoolefinic and methyl branched) have been converted via their mesylates into various long chain alkylated aromatic compounds with basic character, and their mass spectra compared. The spectra of 2-alkylaminopyridines and to some extent those of 3-alkylaminopyridines exhibit most clearly the structure of the aliphatic chain, allowing the localization of branchings and double bonds.

Notes: The title compounds 14-16 were obtained via an intramolecular Mannich condensation by treating 11-13 with CH2O at RT. The unsaturated ketones 14 and 15 were reduced to the allylic alcohols 18 and 19 respectively. Ring cleavage of compound 18 on treatment with 2N HCl gave the substituted aminopropanol 20. The allylic alcohols 18 and 19 were hydrogenated to 22 and 23 respectively. With CH2O, the amino-alcohol 23 gave the methano-naphthoxazocine 24, whereas 22 and 23, on heating in polyphosphoric acid (PPA), afforded the naphthazepines 25 and 26 respectively. With organolithium compounds, the unsaturated ketones 14 and 16 gave the teriary allylic alcohols 27-29, which were hydrogenated and dehydrated to the olefins 36-40; these were cyclized via an intramolecular alkylation to the methanodibenzo-octahydrocyclooctapyridines 41-43. On heating in PPA, the allylic alcohol 29 was converted into the naphthazepine 44. With CH2O, the naphthol 49 gave the naphthoxazocine 50, in equilibrium with the spiro-naphthalene-pyrrolidinone 51 in solution. Finally, in the presence of CH2O, the naphthazepine 57 afforded the methano-naphthazepinone 58, which, by a 4-stage degradation, was transformed to the benzisoquinoline 62.

Notes: The dianions of phenanthrene and 1,2,3,4-dibenzocyclooctatetraene have been prepared by metal reduction of the neutral compounds and characterized via the study of their 1H- and 13C-NMR. spectra. A description of the charge distribution can be achieved which is consistent with both MO-models and the spin density distribution of the corresponding radical anions. Thus, the dianion of 1,2,3,4-dibenzocyclooctatetraene appears as a π-bond delocalized species having its excess charge mainly localized in the eight membered ring.

Notes: An ab initio theoretical study of all fifteen fully staggered conformations of aminodihydroxymethane, CH(OH)2NH2 has been performed. Optimization of the C—O and C—N bond lengths, population analyses and orbital localisation reveal the presence of marked conformation dependent stereoelectronic effects which influence bond lengths and overlap populations. These effects may be parametrized as a function of number and nature of antiperiplanar (app) oriented electronic lone pairs (1p) and polar bonds. In a Y—C—X fragment an app orientation between a lone pair on Y and the C—X bond increases the length and weakens the C—X bond, shortens and strengthens the C—Y bond. Thus a C—X (X = O, N) bond of CH(OH)2NH2 is longest and weakest when: (i) it is app to two vicinal lp's; (ii) the X 1p's are not app to a vicinal polar bond; (iii) the conformation of the molecule has as many axially oriented lp's as possible. Results (i) and (ii) agree with a simple hyperconjugation picture involving interaction between an electronic 1p and an app oriented antibonding bond orbital σ* (C—X). Bond properties, relative energies and effects on reactivity of the tetrahedral species are discussed, as well as their relations to experimental results on the cleavage of tetrahedral intermediates and to enzyme catalysis.

Notes: Metal reduction of the polycycle 2 yields a surprisingly stable dianion with intact molecular framework. This conclusion can be drawn from reoxidation experiments and from an analysis of the 1H-NMR. spectrum. The excess charge turns out to be distributed over both the π- and σ-fragments of the molecule. The relative stabilities of ionic species derived from 1, 2 and 3 are considered.

Notes: [2+2]-Cycloadditions and -cycloreversions in radical anions. An ESR. spectroscopic study for 2,2′-disubstituted diphenyl derivativesThe radical anions derived from the polycyclic olefins 1, 2 and 3 are shown by ESR. spectroscopy to undergo [π2+π2]-cycloaddition reactions even at low temperatures. Similarly, facile cleavage by [σ2+σ2]-cycloreversion processes is observed for the radical anions of the corresponding cyclobutane species. This reactivity, which is in marked contrast with the thermal stability of the neutral parent compounds, is discussed taking into account the molecular geometry and the spin density distribution.

Notes: The 13C- and 17O-chemical shifts of 31 aliphatic ethers are measured and discussed. The 17O-chemical shifts of the ethers ROR′ correlate with chemical shifts for the methylene groups of the corresponding alkanes RCH2R′. The constant of proportionality can be related to the orbital expansion term 〈r-3〉2p. The δc for carbon atoms can also be correlated with δc for the corresponding alkanes. The origin of the correlation is discussed taking into account the conformational modifications resulting from introduction of an oxygen atom in an alkyl chain.

Notes: Gas liquid chromatography allowed isolation of the novel cis-2-isopropenyl-8-methyl-1,2,3,4-tetrahydro-1-naphthalenol (A) and its dehydration product, 3-isopropenyl-5-methyl-1,2-dihydronaphthalene (B), from two small subfractions of Virginia tobacco condensate. Both these norsesquiterpenes were identified on spectral grounds and synthesized from 1-methylnaphthalene in a way (9 steps) that also afforded the «non-natural», trans-alcohol A′. The possible biogenesis of A and B in tobacco is briefly outlined.

Notes: The Zip-reaction: A New Method for the Synthesis of Macrocyclic PolyaminolactamsThe 21- and 25-membered aminolactams 11 and 25 were synthesized from the 13-membered lactam 4. To introduce the ring enlargement unit (a propylamino group) 4 was N-alkylated using acrylonitrile and the resulting product hydrogenated. Repetition of this reaction sequence gave 3, which was converted in the presence of base in 90% yield to the ring-enlarged macrocyclic base 11 (Scheme 2). In a similar but stepwise synthesis consisting of two separate ring-enlargement reactions 4 was transformed to 11 via 13 (Scheme 4). Introducing three ringenlargement units into 4 the 25-membered aminolactam 25 was synthesized in 84% yield (Scheme 5). The mechanism of the ring-enlargement reaction is given in Scheme 3. In comparison to a zip-fastener or zipper this reaction is called “zipreaction”.

Notes: Phytochemistry of genus Gentiana, XXIV. New C-glycosylflavones from the leaves of Gentiana asclepiadea L.p-Hydroxybenzoyl-2″-isoorientin-4′-O-β-D-glucoside (1) was isolated from the leaves of Gentiana asclepiadea L. by means of column chromatography. This is the first occurrence in nature of a p-hydroxybenzoate of isoorientin. p-Hydroxybenzoyl-2″-isoorientin (2) was also shown to be present in the same plant.

Notes: The structure of vinyl amine and its reactivity towards a proton is studied by the PRDDO SCF MO method. The equilibrium structure is found to be non-planar and barriers to inversion- and rotation-dominated processes are calculated. Proton addition to vinyl amine, as a model of enamine protonation, is examined by means of electrostatic molecular potentials and C- versus N-proton affinities.

Notes: Electrochemical Formation of Δ1,2-NorborneneThe electrochemical reduction of 1,2-dihalogen norbornanes in tetrahydrofuran/furan leads to a mixture of two isomeric cycloadducts 6 and 7. The ratio of these adducts corresponds to those which have been found in reductive bisdehalogenation of 1 and 2 by butyllithium.

Notes: The general reactivity of various sites in the vindoline series has been investigated. The facility of electrophilic substitution at C(15) and the effect of steric crowding on reactions at C(4) are discussed. At the basic nitrogen sites, oxidations with mercuric acetate and potassium permanganate are also discussed.

Notes: Study of the flavonic and xanthonic compounds in the leaves of Gentiana ciliata L.Fifteen 1,3,7,8-oxygenated xanthones (1-15) were isolated from the leaves of Gentiana ciliata L. (genus Gentianopsis). Among these were six new glycosides: glucosyl-1-decussatin 6, glucosyl-1-gentiacaulein (8), primeverosyl-8-isogentiacaulein (9), glucosyl-3-isogentiacaulein (10), glucosyl-1-swertianin (12) and primeverosyl-7-swertianin (13). Three known flavone C-glucosides were also found (16-18).

Notes: Three kinds of polar substitutent effects are observable in the solvolyses of 1-R-substituted 3-bromoadamantanes (VI). This follows from the relationship between products, rate constants k in 80% ethanol, and the inductive substituent constants σ1q of the substituent R. Alkyl groups and electron-attracting substituents at C (1) control the rate by their inductive effects alone, since logk correlates closely with σ1q. However, rates are higher than predicted on the basis of the respective σ1q values when conjugating (+ M)-substituents or electrofugal groups are attached to C(1). These exalted substituent effects are attributed to CC-hyperconjugative relay of positive charge from the cationic center at C(3) to the substituent at C(1). When the substituent is a strong electron donor (e.g. O- and S-), accelerated substitution gives way to heterolytic fragmentation, rates and products then being controlled by the frangomeric effect.

Notes: A synthetic model of the active site of the coenzyme B12 dependent methylmalonyl-CoA mutaseThe synthesis of a bridged cobaloxime with a built-in methylmalonic ester moiety is described. 2-Brommethyl-2-methylmalonic acid dichloride (5) afforded upon reaction with 5-heptin-1-ol (4) the corresponding diester 6. Subsequent treatment of 6 with ozone, dimethylsulfide and hydroxylamine hydrochloride led to the pentadentate ligand: 10-brommethyl-10-methyl-9, 11-dioxo-8, 12-dioxa-nonadecane-2, 3, 17, 18-tetraone tetraoxime (8). Reaction of 8 with cobalt (II) chloride, pyridine and sodium borohydride furnished in 7% yield the bridged cobaloxime 10, which was spectroscopically characterized. Short term irradiation of 10 in methanol caused the exchange of the axial pyridine ligand by a solvent molecule affording 10a, the structure of which has been determined by X-ray crystallography. Long term irradiation of 10 in methanol or ethanol led to irreversible cleavage of the Co, C-bond. Upon alkaline hydrolysis the degradation product afforded methylsuccinic acid in 82-95% yield. No incorporation of solvent protons into this product could be observed. Implications of these findings for the mechanism of the coenzyme-B12 catalysed rearrangement of methylmalonyl-CoA are discussed.

Notes: “Push-Pull” Acetylenes as Reagents for Peptide SynthesisA series of ‘push-pull’ acetylenes 1 is easily available from the corresponding “push-pull” olefins by a simple bromination-dehydrobromination sequence. The versatility of the acetylenes with regard to peptide synthesis is discussed.

Notes: 1, 4, 5, 6-Tetrahydro-ν-tetrazin-DerivateThe title compounds 2 and 13 are readily available from α-lithiated N-alkyl-nitrosoamines 1 (see Tables 1 and 2) which decompose at - 73° to yield the N-oxides 2. The ESR. spectra of two derivatives 1 are recorded (Fig. 1), and tentative mechanisms are proposed for the head to head dimerizations (la- 3- 4- 5- 2a and Scheme 1). Coupling of lithionitrosoamines with iodine (-6) and alternative decomposition routes of representatives of this class of organometallics with special substitution [equations (2)-(5)] are reported.The structures of the tetrazines are established by spectroscopic data [ESCA] (Fig. 2), IR., UV., 1H- (cf. Fig. 9) and 13C-NMR., PE. (Scheme 2), by an X-ray analysis of 2a (Fig. 4-8 and Table 3), and by the chemical reactions. The crystal structure of 2a is a twisted boat with non planar terminal nitrogen atoms which reflects the electron repulsion in the 4-atom-6-electron N—N=N≡N-system. Comparisons are made with 2-tetrazenes, the open chain analogues of 13, wherever possible. Raney-Ni reductions of 2 or 13 gives diamines 14 to which is assigned the d, l-configuration through the 1H-NMR. spectra of the aminals 7 and 15. Neither the oxides 2 nor the tetrazines 13 undergo cycloaddition reactions [equation (6) and Section 4].Compound 2a is dimerized to the bis (nitrosoamino)-2-tetrazene 18 by treatment with acid, ZnII, CuI or iodomethane. 2a is oxidized at nitrogen to the ethylene diamine derivative 6a (through 20, with H2O2), or at the CH2-groups of the ring to give oxo-N-oxide 21 (with MnO2 or the ring contracted oxo-tetrazoline-N-oxide 22 (with KMnO4).Pyrolysis or photolysis of the dimethyl tetrahydrotetrazine 13a furnishes the trimer 26 of N-methylimine, but no diazetidine 27. Silver and mercury complexes 29 are obtained from 13a, while Cr(CO)5. THF does not furnish a complex as with azocompounds, but rather replaces N2 in 13a by CO (→ 28). Oxidation with permanganate converts 13a into the oxalic acid derivative 30 with unchanged tetrazine structure.

Notes: A simple one-pot method for esterificationA one-pot procedure for esterifications of primary, secondary and tertiary alcohols and of phenols in high yield is described. Reaction of oxalylchloride with dimethylformamide in a suitable solvent affords dimethylformamide imidechloride; addition of an acid to the suspension of this reagent furnishes an activated carboxy-group derivative, which is then transformed to an ester by addition of pyridine and an alcohol ro a phenol. Reaction temperatures needed for esterification are low, usually 0° to room temperature, reaction times are short.

Notes: Cyclooct-1-en-5-yne (3) has been obtained as an isolable, but highly reactive hydrocarbon by oxidation of cyclooct-5-ene-1, 2-dihydrazone with lead tetraacetate (Scheme 2). Information regarding the structure and conformational mobility of 3 has been gained from the analysis of its 1H- and 13C-NMR. spectra and was found to agree with the results of force field calculations. Photolysis (206 nm) of 3 in solution has induced cleavage to butatriene and butadiene. The first band in the photoelectron spectrum of 3 (Iv 9.10 eV) is attributed to ionization from a rather delocalized orbital with predominant weight of the double bond p-AO's. Nevertheless, the high reactivity of 3 stems from the strained triple bond as evidenced by the reaction products obtained by pyrolysis, oxidation, Diels-Alder addition, and 1, 3-dipolar addition (Scheme 4).

Notes: Nucleosides and Nucleotides, Part 11. Phosphorylation of 1-(2′-Desoxy-β-D-ribofuranosyl)-2(1H)-pyridon and its Behaviour in the Synthesis of DinucleotidesThe behaviour of the unnatural nucleoside 1-(2′-deoxy-β-D-ribofuranosyl)-2(1H)-pyridon (Πd, 1) in the synthesis of dinucleotides with purine deoxynucleotides was studied. The optimized preparation of the protected dinucleoside phosphates (MeOTr) Πd pGibd (5) and (MeOTr) Πd pAbzd (7) using the diester method of Khorana with DCC as condensing agent is described. The removal of the N-acyl- and p-methoxytrityl groups was effected by successive treatment with conc. ammonia solution and acetic acid/water 1:1 at 23° yielding the free dinucleoside phosphates ΠdpGd (9) and ΠdpAd (11). In a similar way, starting from (CNEt) pΠd(15), the dinucleotides pΠdpGibd (16), pΠdpGd (18), pΠdpAbzd (17) and pΠdpAd (19) were synthesized.The nucleotide 1-(5′-O-Phosphoryl-2′-deoxy-β-D-ribofuranosyl)-2(1H)-pyridon (pΠd, 3) was prepared in excellent yield by selective phosphorylation of Πd (1) using phosphorylchloride in triethyl phosphate at -40°. Deoxyadenosine was phosphorylated in the same way.The compounds were characterized by UV. spectroscopy, chromatography and enzymatic degradation.