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Notes: Abstract. Despite its lack of specificity, magnetic resonance imaging (MRI) of the bone marrow has the potential to play a role in the management of patients with primary neoplastic disorders of the hematopoietic system, including lymphomas, leukemias and multiple myeloma. In addition to its use in the assessment of suspected spinal cord compression, bone marrow MRI could be used as a prognostic method or as a technique to assess the response to treatment. The current review addresses the common patterns of bone marrow involvement observed in primary neoplasms of the bone marrow, basic technical principles of bone marrow MRI, and several applications of MRI in selected clinical situations.

Notes: Abstract. One case of malignant schwannoma of the sacrum and another of occipital osteoblastoma were evaluated by MR imaging. Both tumors showed fluid-fluid levels with different signal intensities in the sequences performed. Pathologic examination revealed hemmorhagic fluid in both tumors. Malignant schwannoma and osteoblastoma should be included in the list of bone and soft-tissue with fluid-fluid levels. Our data confirm the non-specificity of this finding, which only suggests the presence of previous intratumoral hemorrhage.

Notes: Abstract. The rectum has become the most successful area of the gastrointestinal tract to be studied with MRI. Its anatomical location, fixed in the pelvic fat, and its lack of peristalsis, make it an ideal organ to be scanned with MRI. In addition, MRI allows a direct sagittal and coronal display, of key importance to colorectal surgeons whose terminology and approach are based on the coronal plane. The sagittal plane allows the depiction of the relation of the rectum to the sacrum, uterus and prostate, with detail not available by other imaging techniques, and the use of endorectal coils allows excellent demonstration of the rectal wall. Although MRI has been used primarily to study rectal carcinoma, other diseases, congenital, inflammatory and vascular in origin, can be studied using the correct technique.

Notes: Abstract. Disc prolapse presenting with sciatica may be associated with enhancement of the symptomatic nerve root following magnetic resonance imaging (MRI) with intravenous gadolinium (Gd)-DTPA. Previous studies have shown, however, that this does not occur in all cases. The aim of this study was to assess the incidence of nerve root enhancement in patients with sciatica and disc prolapse and to try to identify any specific features that might be associated with the phenomenon. A total of 227 patients presenting with low back pain and/or sciatica underwent a MRI study of the lumbar spine with intravenous contrast enhancement. Nineteen of 81 (23.5 %) patients with disc prolapse demonstrated nerve root enhancement. Nerve root enhancement had a highly significant association with sequestrated disc lesions (13/19, 68 %; P 〈 0.0005), and was primarily seen in the symptomatic ipsilateral nerve root (16/19, 84 %). The sensitivity of nerve root enhancement associated with disc prolapse was 23.5 % with a specificity of 95.9 %, a positive predictive value of 76 % and a negative predictive value of 69.3 %. Nerve root enhancement may be indicative of the symptomatic level but its poor sensitivity negates the routine use of Gd-DTPA in MRI for sciatica.

Notes: Abstract. We report a rare case of a young girl with an embryonal rhabdomyosarcoma of the right aryepiglottic fold. Local disease recurrence, occurring 7 years after subtotal resection and adjuvant chemotherapy, was studied with plain radiography, CT and MRI. To the best of our knowledge, this is the first report illustrating the MRI characteristics of a laryngeal embryonal rhabdomyosarcoma in a child.

Notes: Abstract Osseous lipomata of vertebral bodies are rare. We present a very unusual case where adjacent vertebrae are involved and the plain radiographic and scintigraphic appearances gave cause for some concern. The findings on plain films, scintigraphy, computed tomography and magnetic resonance imaging are discussed.

Notes: Abstract We report a 2-year prospective neuropsychological study of five asymptomatic subjects with magnetic resonance imaging (MRI) abnormalities from an Italian kindred affected by cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). These subjects completed tests for attention capacities, processing speed, abstract thinking, short-term memory, learning and constructional praxis. Seven normal subjects matched for age and education, belonging to the same pedigree and not having MRI hyperintensities were examined as controls. The results did not show significant differences between asymptomatic subjects and normal controls. Cognitive performance of asymptomatic subjects did not deteriorate during a 2-year follow-up. Our findings suggest that, at this stage of the disease process, the presence of diffuse leukoencephalopathy does not imply subtle cognitive defects.

Notes: Abstract The aim of the present study was to assess selective atrophy of the temporal lobe and amygdala in the early stages of Alzheimer dementia (AD). Magnetic resonance imaging (MRI) measurements and the presence of highsignal lesions (HSL) were analysed in 31 patients with mild to moderate probable AD and 22 controls. In the AD group, MRI findings were compared with cognitive variables and specific features of memory functions. Alzheimer patients showed a significant reduction in volumetric measurement compared with controls in the total volume (P 〈 0.01), temporal lobe (P 〈 0.01) and amygdala (P 〈 0.05). The temporal lobe/brain volume ratio was also significantly reduced in AD subjects (P 〈 0.05). Atrophy of temporal structures was significantly related to the degree of episodic and semantic memory impairment according to a material-specific effect. No significant correlations between amygdala and cognitive variables were found. The results of our study confirm the usefulness of measures of temporal lobe atrophy assessed with MRI in the diagnosis of AD. In contrast, HSL are relatively common in AD patients (12/31 cases) and were not related to volumetric findings, severity of dementia or functional disability.

Notes: Abstract. The postpartum magnetic resonance imaging (MRI) appearance of a patient with placenta accreta and abscess formation is presented here and compared to the ultrasound and CT findings. The diagnosis was confirmed on histopathologic examination and cultures of the hysterectomy specimen. On MRI, the T1-weighted acquisitions showed an enlarged uterus of mildly heterogeneous but predominantly low signal intensity. The T2-weighted images demonstrated a heterogenous area of predominantly bright signal within the uterine body and fundus. In this case, MRI was more informative than ultrasound and non-contrast CT scan in the postpartum diagnosis of placenta accreta with abscess formation.

Notes: Abstract The authors conducted a study of 21 children with benign astrocytomas in the IV ventricle treated with radical tumor resection from 1982 through 1991. The purposes of this study were to identify the tumor origin and neural involvement, and to determine the natural history following surgical resection. Pathological studies showed that 18 were pilocytic astrocytomas (pure pilocytic in 12, mixed in 6), 2 fibrillary, and 1 gemistocytic. In the IV ventricle, 12 patients had a transependymal involvement of the floor (brain stem), 6 had an involvement of the wall (cerebellar peduncle), and 3 had involvement of both floor and wall. A gross total resection was performed in 9 patients, and the remaining 12 patients underwent a subtotal resection. All patients were followed without radiation therapy (RT) or chemotherapy. During a follow-up period of 6.5–15 years, all patients were alive. Eight patients suffered recurrence between five months and 66 months after diagnosis. Of these, five received RT for recurrence and had a complete response in all cases. The remaining 13 patients showed no evidence of disease and one had a stable residual tumor. The recurrence-free 5-year and 10-year survival rates were 62.5% and 57% respectively. Patients without brainstem involvement, with total resection, or with pure pilocytic astrocytoma had a better outcome than those with brain stem involvement, with subtotal resection, or with nonpilocytic or mixed histology. In summary, a great majority of benign IV ventricle astrocytomas involve the floor of the IV ventricle. It is often difficult to determine the origin of these tumors in most cases. Benign IV ventricle astrocytomas may not recur even after incomplete resection, and close observation without RT is recommended, although RT appears to be effective for these tumors when they recur.

Notes: Abstract A 16-year-old boy with the classic or postinfantile type of Hallervorden-Spatz syndrome is described. Bilateral optic atrophy with visual loss but without retinal changes was the only presenting symptom. Mild cognitive impairment, behavioural disturbances and insidious extrapyramidal involvement appeared later. MRI showed marked symmetrical hypointensity of the globi pallidi and substantia nigra. This new observation suggests that the occurrence of optic atrophy in a patient with Hallervorden-Spatz syndrome should be regarded as noncoincidental and stresses the importance of an accurate neurological work-up in all adolescents with any unusual form of progressive optic atrophy.

Notes: Abstract  Objective. To define and compare early lesions associated with slipped capital femoral epiphysis (SCFE) on magnetic resonance imaging (MRI), computed tomography (CT) and radiography. Design and patients. Thirteen patients with 15 symptomatic hips due to SCFE underwent radiography and MRI; CT was performed in 12 patients. SCFE was graded on radiographs, head/neck angles and qualitative changes were evaluated on CT, and morphologic/signal abnormalities were determined on MRI. Results. Physeal widening, apparent on T1-weighted MRI, was evident in every case of SCFE, including one presumed “pre-slip.” T2-weighted images demonstrated synovitis and marrow edema but obscured physeal abnormalities. CT head/neck angles ranged from 4–57° for symptomatic to 0–14° for asymptomatic hips. Physeal and metaphyseal changes were variably identified on both radiographs and CT in all cases of SCFE, but not in the pre-slip. Conclusion. MRI clearly delineates physeal changes of both pre-slip and SCFE, and demonstrates very early changes at a time when radiographs and CT may appear normal.

Notes: Abstract  A 33-year-old patient with a 2-year history of intermittent pain in the right gluteal region and thigh presented with a large sclerotic lesion of the iliac bone. From the findings on radiography, scintigraphy, CT and MRI, a giant parosteal osteoma was suspected. The histological examination confirmed the diagnosis. Since the lesion was extensive it was observed with periodic follow-up examinations. At present, 5 years after the diagnosis, the patient is asymptomatic and imaging studies show that the lesion persists with reduction of sclerosis and size. The tumor was on the surface as well as intramedullary – only one other case with such a distribution is known to us – and it was also in the iliac bone.

Notes: Abstract  Objective. Granuloma annulare is an uncommon benign inflammatory dermatosis characterized by the formation of dermal papules with a tendency to form rings. There are several clinically distinct forms. The subcutaneous form is the most frequently encountered by radiologists, with the lesion presenting as a superficial mass. There are only a few scattered reports of the imaging appearance of this entity in the literature. We report the radiologic appearance of five cases of subcutaneous granuloma annulare. Design and patients. The radiologic images of five patients (three male, two female) with subcutaneous granuloma annulare were retrospectively studied. Mean patient age was 6.4 years (range, 2–13 years). The lesions occurred in the lower leg (two), foot, forearm, and hand. MR images were available for all lesions, gadolinium-enhanced imaging in three cases, radiographs in four, and bone scintigraphy in one. Results. Radiographs showed unmineralized nodular masses localized to the subcutaneous adipose tissue. The size range, in greatest dimension on imaging studies, was 1–4 cm. MR images show a mass with relatively decreased signal intensity on all pulse sequences, with variable but generally relatively well defined margins. There was extensive diffuse enhancement following gadolinium administration. Conclusion. The radiologic appearance of subcutaneous granuloma annulare is characteristic, typically demonstrating a nodular soft-tissue mass involving the subcutaneous adipose tissue. MR images show a mass with relatively decreased signal intensity on all pulse sequences and variable but generally well defined margins. There is extensive diffuse enhancement following gadolinium administration. Radiographs show a soft-tissue mass or soft-tissue swelling without evidence of bone involvement or mineralization. This radiologic appearance in a young individual is highly suggestive of subcutaneous granuloma annulare.

Notes: Abstract  Objective: To study magnetic resonance (MR) imaging pattern of normal hyaline articular cartilage in the knee joint with regard to the contribution of the “magic angle” effect to the MR signal. Design. Thirty-two healthy volunteers were imaged in a standard supine position in a 1.5-T unit using spin echo and gradient echo sequences. Nine volunteers were reimaged with the knee flexed. The signal behavior of the hyaline cartilage of the femoral condyles was evaluated qualitatively and quantitatively. The extended and flexed positions of the nine volunteers were compared. Results. A superficial and a deep hyperintense layer and a hypointense middle cartilage layer were observed. Segments of increased signal intensity were visible along the condyles; a magic angle effect on signal intensity was evident in the hypointense middle layer with both gradient echo and spin echo images. Conclusion. The MR signal behavior of hyaline cartilage is influenced by the alignment of the collagen fibers within the cartilage in relation to the magnetic field. Failure to recognize this effect may lead to inaccurate diagnosis.

Notes: Abstract A 14-year-old boy presented acutely with occipital headache, nausea and vomiting. MRI showed obstructive hydrocephalus and marked bilateral cerebellar swelling with increased signal on T2-weighted imaging. Following treatment with oral corticosteroids, the clinical and radiological signs resolved. The clinical course and radiological appearances were consistent with cerebellitis associated with a significant mass effect and hydrocephalus.

Notes: Abstract We report the case of a 13-year-old girl with diffuse bilateral thalamic astrocytomas. Incoordination was observed at the onset. Cranial computed tomography (CT) showed enlarged thalami, and magnetic resonance imaging (MRI) revealed these lesions to be symmetrically enlarged with high intensity on the T2-weighted image. Owing to these atypical findings in the neuroimaging studies, we had difficulty in making the correct diagnosis of a brain tumor. After the diagnosis of diffuse bilateral thalamic astrocytomas was obtained, we performed hyperfractionated radiotherapy followed by chemotherapy. Radiation therapy was effective for a while, but the girl's condition deteriorated again and she died 8 months after admission. Although diffuse bilateral thalamic astrocytomas are difficult to diagnose because they do not resemble most other neoplasms on neuroimaging studies, pediatricians should keep this entity in mind in order to arrive at a precise and prompt diagnosis.

Notes: Abstract A cyst of the choroid plexus of the left lateral ventricle with intermittent blockage of the foramen of Monro and initially with invagination of the III ventricle in a child is described. In a 6-week-old boy a ventriculoatrial shunt was implanted for correction of an active asymmetrical hydrocephalus of unknown origin. When he was 3 months of age a water-soluble contrast CT ventriculography revealed a noncolloid cyst localised predominantly in the upper portion of the III ventricle. At that time the ventricular catheter obstructed with choroid plexus was removed; new bilateral catheters in a parieto-occipital region were implanted. In the course of the next 4 years, first the atrial catheter had to be extracted and then the peritoneal catheter was changed, in both cases because of obstruction. Periods of normal life alternated with periods of transient and intermittent symptoms of increased intracranial pressure, papilloedema, and myoclonic jerks. Repeated computed tomography (CT) and magnetic resonance imaging (MRI) showed stabilised hydrocephalus with an enlarged left lateral ventricle. When the boy was 16 years old MRI revealed a choroid plexus cyst in the left lateral ventricle 2 cm in diameter, with a ball-valve type of obstruction of the foramen of Monro. CT stereoendoscopic resection of the wall of a large cyst filled with cerebrospinal fluid was performed, and two additional adnexal small cysts were coagulated using the bipolar coagulator, Diomed 25 laser and scissors; the symptoms then regressed, except for superior bilateral altitudinal anopsia. Light and electron microscopy of the cyst wall is reported. The cyst was composed of collagenic connective tissue lined with a basal lamina lacking in epithelial cells. The preoperative and postoperative MRI are presented. Choroid plexus cysts localised in the anterior part of lateral ventricles are very rare, and all reported cases have been in male patients. According to the literature our case is only the third ever described in a child.

Notes: Abstract We present the rare case of a girl surviving intrauterine listeria brain stem meningoencephalitis, who subsequently developed hydrocephalus, a trapped IV ventricle and an intramedullary cyst. Such cases have been reported only infrequently, and in earlier cases modern imaging studies were not available. Magnetic resonance imaging has been helpful in our patient to delineate the lesions and plan further treatment.

Notes: Zusammenfassung Fragestellung: Beeinflussen Form und Größe des präoperativen peritumoralen Hirnödems die Rezidiventwicklung bei malignen supratentoriellen Gliomen? Methodik: Prospektiv wurden 79 Patienten mit einem malignen supratentoriellen Gliom mit einem standardisierten MRT-Protokoll untersucht. MRT-Untersuchungen erfolgten vor der neurochirurgischen Operation, möglichst innerhalb der ersten 3 Tage nach Operation und während der Nachbeobachtungszeit in Abständen von 2–3 Monaten. Die mediane Nachbeobachtungszeit betrug 11 Monate. Die initiale präoperative Ödemkonfiguration auf den T2-gewichteten MRT-Aufnahmen wurde mit der Rezidivtumorkonfiguration auf den Kontrastmittel verstärkten T1-gewichteten Aufnahmen verglichen. Ergebnisse: 47 Patienten entwickelten während der Nachbeobachtungszeit ein Rezidiv. Die Konfiguration des Rezidivtumors imitierte in 35/47 Patienten (75%) die initiale präoperative Ödemkonfiguration. Bei 11/47 Patienten entwickelte sich ein lokales und bei einem Patienten ein multilokales Rezidiv. Schlußfolgerungen: Die präoperative Tumorödemkonfiguration im T2-gewichteten MRT-Bild korreliert mit der Rezidivtumorausdehnung. Zukünftige Therapiestudien sollten daher die Ausdehnung des initalen präoperativen Ödems als zusätzlichen prognostischen Faktor mitberücksichigen.

Notes: Abstract The authors have previously reported decreased intracellular pH (pHi) in the frontal lobes in euthymic bipolar patients treated with lithium using 31P-MRS. White matter hyperintensity (WMHI) is frequently seen in bipolar disorder. To examine a possible effect of lithium on pHi and the relationship between pHi and WMHI, seven drug-free euthymic bipolar patients were examined, and T2-weighted MRI were examined in 14 previously reported bipolar patients. Drug-free patients showed significantly lower pHi than controls. WMHI was associated with low pHi and increased phosphodiester peak. These results suggest that decrease of pHi is not an effect of lithium but is instead related to the pathophysiology of illness. Decrease of pHi and increase of the PDE peak may be the biochemical basis of WMHI in bipolar disorder.

Notes: Zusammenfassung Die Diagnose der im Jugendalter spontan auftretenden Epiphysiolysis capitis femoris wurde bislang anhand der klinischen Beschwerden sowie der Bestimmung des Abrutschwinkels in konventionellen Aufnahmen (Beckenübersicht, Aufnahme nach Rippstein) gestellt. Für die Diagnose der Frühformen der Epiphysiolysis capitis femoris exsistiert kein allseits akzeptierter Goldstandard. Ziel der vorliegenden Arbeit war es herauszuarbeiten, inwieweit die Epiphysiolysis capitis femoris charakteristische Zeichen in der Kernspintomographie bietet und ob die MRT in der Lage ist, früher Veränderungen als die konventionellen Methoden zu erkennen. Die Kernspintomographien (1,5-T-, T1- und T2-SE-Sequenzen koronar, sagittal, paraaxial, fakultativ STIR-, TIRM-, FLASH-2D-Sequenzen) von fünf gesunden Kindern wurden standardisiert analysiert und mit den magnetresonanztomographischen Untersuchungen von neun Patienten mit vermuteter Epiphysiolysis capitis femoris verglichen. Bei den neun Patienten lagen zusätzlich konventionelle Röntgenaufnahmen nach Rippstein vor. Im Normalkollektiv stellte sich die Epiphysenfuge homogen signalarm bzw. signalfrei dar. Sie wies eine konstante Weite bis zu 3 mm auf und war gegenüber den angrenzenden knöchernen Strukturen scharf abgegrenzt. Das Grenzflächensignal erschien homogen und gezähnelt. Patienten mit vermuteter Epiphysiolysis capitis femoris zeigten eine Erweiterung der Epiphysenfuge auf mehr als 3 mm in sechs von neun Fällen. Bei allen klinisch verdächtigen Fällen konnte ein Gelenkerguß abgegrenzt werden. Es fand sich zusätzlich eine Verschiebung oder Abflachung der Verzähnelung. Ein Signalanstieg im Bereich des Knorpels fand sich kernspintomographisch in nur zwei Fällen.

Notes: Abstract. The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-d-glucose (18F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for 18F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the ”Japanese reference man” to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1×10–1, 3.7×10–2 and 2.8×10–2 mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9×10–2 mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1×10–2 mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered 18F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.

Notes: Abstract. Although ictal single-photon emission tomography (SPET) with technetium-99m ethyl cysteinate dimer (ECD) has a well-established role in the diagnostic evaluation of patients with temporal lobe epilepsy who are being considered for epilepsy surgery, its use in cases of extratemporal epilepsy is still limited. We investigated the influence of the propagation of extratemporal epileptic seizure activity on the regional increase in cerebral blood flow, which is usually associated with epileptic seizure activity. Forty-two consecutive patients with extratemporal epilepsies were prospectively evaluated. All patients underwent ictal SPET studies with simultaneous electroencephalography (EEG) and video recordings of habitual seizures and imaging studies including cranial magnetic resonance imaging and positron emission tomography with 2-[18F]-fluoro-2 deoxy-d-glucose. Propagation of epilptic seizure activity (PESA) was defined as the absence of hyperperfusion on ictal ECD SPET in the lobe of seizure onset, but its presence in another ipsilateral or contralateral lobe. Observers analysing the SPET images were not informed of the other results. PESA was observed in 8 of the 42 patients (19%) and was ipsilateral to the seizure onset in five (63%) of these eight patients. The time between clinical seizure onset and injection of the ECD tracer ranged from 14 to 61 s (mean 34 s). Seven patients (88%) with PESA had parieto-occipital epilepsy and one patient had a frontal epilepsy. PESA was statistically more frequent in patients with parieto-occipital lobe epilepsies (58%) than in the remaining extratemporal epilepsy syndromes (3%) (P〈0.0002). These findings indicate that ictal SPET studies require simultaneous EEG-video recordings in patients with extratemporal epilepsies. PESA should be considered when interpreting ictal SPET studies in these patients. Patients with PESA are more likely to have parieto-occipital lobe epilepsy than seizure onset in other extratemporal regions.

Notes: Abstract Solitary fibrous tumors (SFT) arise in the pleura and less commonly in extrapleural sites. Head and neck regions have included the nose and paranasal sinuses, soft palate, epiglottis, thyroid, parotid and submandibular glands, as well as the infratemporal fossa and parapharyngeal space. We report a case of SFT arising from the parotid gland and extending to the parapharyngeal space. To our knowledge, this is the fourth case of SFT originating from the parotid gland and is the largest of its kind among the extrapleural lesions described. The characteristics revealed by computed tomography and magnetic resonance imaging are presented.

Notes: Abstract A patient with tenosynovial tuberculosis affecting the extensor tendons of the wrist and hand is presented. This case highlights the clinical and magnetic resonance features of tuberculous tenosynovitis, and seeks to increase awareness of what may represent a resurgent musculoskeletal entity.

Notes: Abstract The intra-articular injection of a radiopharmaceutical agent (radiosynovectomy) produces a reduction of the synovial inflammatory process. The inflammed synovial membrane can be identified with magnetic resonance imaging after the intravenous administration of gadolinium (MRI-Gd). A 6-month prospective study was carried out in 10 patients with rheumatoid arthritis after radiosynovectomy of the knee. The efficacy was evaluated with clinical parameters and MRI-Gd. A progressive amelioration of synovial effusion, pain, articular range of mobility, total leucocytes count in synovial fluid and synovial membrane thickness through MRI-Gd was observed. The global efficacy was considered to be good in six patients, fair in three and bad in one. The study shows for the first time that MRI-Gd allows the evaluation of the response of the synovial membrane to radiosynovectomy.

Notes: Abstract  The disadvantages and limitations of imaging methods to investigate velopharyngeal incompetence have created some difficulties in the management of this condition. Seven normal volunteers and seven patients who were suffering from a speech disorder were examined using magnetic resonance imaging. The velopharyngeal aperture was evaluated at rest and during phonation. In normal volunteers, the velopharyngeal aperture area had a mean value of 1.632 cm2 while at rest and complete closure was obtained during the phonation of /s/ sound. Detailed information was obtained about the function of the levator palati muscle. In five patients during the phonation of /s/ sound there was an increase in the area of the velopharyngeal aperture when compared to the volunteers. Investigation with magnetic resonance imaging is helpful in the pretreatment evaluation and postopertive follow-up examination of velopharyngeal insufficiency. As a result, this noninvasive method can be used as an alternative to conventional radiological investigations.

Notes: To get informations on both the structure and dynamics of hydrogen chelates 1 of heteroaromatic systems, a great variety of quinazoline-2-acetonitrile chelates were synthesized (see 2-4). Similarly to the situation of the corresponding H-chelates in the pyrimidine-2-acetonitrile series, the investigation of these new derivatives 2-4 by NMR spectroscopic methods (DNMR, COSY, NOESY, ROESY, EXSY, HMQC, HMBC) confirms the presence of an equilibrium of the two possible H-chelate structures (two ‘rotamers’ I and II, i.e., (E)/(Z) isomers; see Scheme). The corresponding equilibria I ⇌ II were determined by complete 1H-NMR signal assignment at low temperatures (after freezing the rotational processes). In addition, the tautomer equilibria A ⇌ B (relative energies of the two minima of the nonsymmetrical double-well potential) for both ‘rotamers’ are ascertained by H,H and C,H couplings. The results are an important basis for the interpretation of both the UV/VIS absorptions and the dependence of fluorescence and fluorescence quantum yields on temperature.

Notes: Stereoselective reactions of phthalimido-substituted radicals derived from (±)-threonine with different radical traps are reported (Scheme 3, Table 1). A strong influence of the nature of the radical trap on the stereoselectivity was noticed. Small nucleophilic radical traps gave preferentially the syn products. The observed selectivities are explained with the A1,3 strain model and depend on steric and electronic effects (Fig. 2). Reactions with electrophilic radical traps such as diphenyl diselenide gave the anti diastereoisomers with moderate stereocontrol, presumably due to stereoelectronic effects. The same stereochemical outcome, i.e., preferential formation of the anti products, was observed for the reactions of the related N-phthaloyliminium ion (Scheme 5, Table 2). The stereochemistry of the ionic reaction is rationalized by a Felkin-Anh model (Fig. 3).

Notes: The cyclopalladation of 1,1′-azonaphthalene (= di(naphthalen-1-yl)diazene; 2) with bis(hexafluoroacetyl-acetonato)palladium(II) (3; [Pd(hfa)2]) yields the ortho-palladated complex (1,1,1,5,5,5-hexafluoropentane-2,4-dionato-κ2O,O′)[1-(naphthalen-1-ylazo-κN2)naphthalen-2-yl-κC2]palladium(II) (4) as well as the peri-palladated complex (1,1,1,5,5,5-hexafluoropentane-2,4-dionato-κ2O,O′)[8-(naphthalen-1-ylazo-κN2)naphthalen-1-yl-κC1]-palladium(II) (5); their structures were corroborated by X-ray analyses. The formation of the novel peri-metallated product 5 containing a six-membered palladacycle strongly depends upon the reaction conditions.

Notes: The photoisomerization behavior of three mono[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 1, 2, and 3, and three bis[(E)-3-(4-hydroxyphenyl)prop-2-enoyl]spermidines, 4, 5, and 6, are investigated. The synthetic product (E)-1 could be almost quantitatively (〉 96%) converted into its isomer (Z)-1 under UV light irradiation. In the cases of (E)-2 and (E)-3, a mixture of (E)/(Z) ca. 1:2 was obtained, when the same conditions were applied. The comparison of their UV spectra provides the possible explanation for these different behaviors. Furthermore, it was noticed that the (Z) → (E) isomerization of the C=C bond took place during the purification by reverse-phase high-performance liquid chromatography (RP-HPLC), and the (E)/(Z)-mixture is thus inseparable. The same feature could be observed during the isolation of the (Z,Z)-N,N′-bis[3-(4-hydroxyphenyl)prop-2-enoyl]-spermidines, (Z,Z)-4, (Z,Z)-5, and (Z,Z)-6. Nevertheless, the fractions of (Z,Z)-5 and (Z,Z)-6 were in almost pure state collected, and their 1-NMR spectra are presented.

Notes: The synthesis, absolute configuration, and olfactive evaluation of (-)-(E)-α-trans-bergamotenone (= (-)-(1′S,6′R,E)-5-(2′,6′-dimethylbicyclo[3.1.1]hept-2′-en-6′-yl)pent-3-en-2-one; (-)-1), as well as its homologue (-)-19 are reperted. The previously arbitrarily attributed absolute configuration of 1 and of (-)-α-trans-bergamotene (= (-)-(1 S,6R)-2,6-dimethyl-6-(4-methylpent-3-enyl)bicyclo[3.1. 1]hept-2-ene; (-)-2), together with those of the structurally related aldehydes (-)-3a,b and alcohols (-)-4a,b, have been rigorously assigned.

Notes: (-)-(R)-4,4,4,4′,4′,4′-Hexafluorovaline hydrochloride ((R)-5) of 98% ee is prepared from β,β-bis(trifluoromethyl)acrylic acid (= benzyl 4,4,4-trifluoro-3-(trifluoromethyl)but-2-enoate; 1) in 4 steps with an overall yield of 9.6%. Key step is the separation of the TsOH salts of the diastereoisomers obtained by anti-Michael addition of (+)-(R)-1-phenylethylamine (2) to 1 (→ (R,R)-3). In contrast to the published (S)-chirality, the X-ray structure analysis of (R,S)-6 reveals, that (R)-chirality has to be assigned to the levorotatory (-)-4,4,4,4′,4′,4′-hexafluorovaline hydrochloride.

Notes: The synthesis and characterization of tripodal dodecadentate ligands with salicylamide and bipyridine binding sites for iron(II) and iron(III) are presented.

Notes: The reaction of CuO'Bu with CO2, and iPr2NH in the presence of PPh3, gives the dialkylcarbamato complex [Cu(O2CNiPr2)(PPh3)2] (1). The CO2/R2NH system (R = Me, Et) in an appropriate organic medium reacts with Ag2O giving the corresponding N,N-dialkylcarbamato complexes of analytical formula [Ag(C2CNR2)] (R = Me, 2; R = Et, 3). The methyl derivative 2 was characterized by X-ray diffraction methods. Crystal data of 2: for [Ag2(O2CNMe2)2], C6H12Ag2N2O4, mol. wt. 391.9; monoclinic, space group P21/c, a = 12.08(1), b = 3.797(2), c = 11.316(7) Å, β = 113.37(6)°, V = 476.3 Å3, Z = 2, Dc = 2.732 g cm-3; μ(MoKα) = 40.64 cm-1, F(000) = 376.0; R = 0.059, Rw = 0.067; g.o.f. 1.27. The structure consists of dinuclear [(Ag2OCNMe2)2] units with slightly distorted linearly two-coordinated Ag-atoms containing bridging carbamato groups to form a substantially planar eight-membered ring with an intra-annular Ag—Ag distance of 2.837(2) Å; the dinuclear units are further joined by Ag—O bonds to form an infinite array. Compound 3, which is presumably dinuclear, as suggested by cryoscopic measurements in benzene, undergoes a structural fission with PPh3, giving the mononuclear triphenylphosphine derivative [Ag(O2CNEt2)(PPh3)2] (4). The amine-catalyzed conversion of Ag2O into Ag2CO3, in the presence of the iPr2NH/CO2 system, is also reported. Cl-Exchange from [AuCl(PPh3)] with [Ag(O2CNEt2)] (3) gives the first N,N-dialkylcarbamato complex of gold, namely [Au(O2CNEt2)(PPh3)] (5), which crystallizes in the monoclinic system: C23H25AuNO2P · 0.5 C7H16, mol. wt. 625.5, space group P21/c; a = 13.212(5), b = 12.25(1), c = 16.795(6) Å, β = 109.09(2)°, V = 2568(2) Å3, Z = 4, Dc, = 1.618 g cm-3; μ(AgKα) = 31.40 cm-1, F(000) = 1236.0; R = 0.058; Rw = 0.064; g.o.f. 2.121. The compound contains two-coordinated Au-atom, namely to the P-atom and to the O-atom of the monodentate carbamato group, the P—Au—O bond angle being 174.7(3)°. The reaction with MeI showed these compounds to react predominantly at the carbamato O-atom giving the corresponding urethanes R2NCO2Me. Evidence was gathered for the transient coordination of CO to Ag in 3.

Notes: The reactions of α-diazo ketones 1a,b with 9H-fluorene-9-thione (2f) in THF at room temperature yielded the symmetrical 1,3-dithiolanes 7a,b, whereas 1b and 2,2,4,4-tetramethylcyclobutane-1,3-dithione (2d) in THF at 60° led to a mixture of two stereoisomeric 1,3-oxathiole derivatives cis- and trans-9a (Scheme 2). With 2-diazo-1,2-diphenylethanone (1c), thio ketones 2a-d as well as 1,3-thiazole-5(4H)-thione 2g reacted to give 1,3-oxathiole derivatives exclusively (Schemes 3 and 4). As the reactions with 1c were more sluggish than those with 1a,b, they were catalyzed either by the addition of LiClO4 or by Rh2(OAc)4. In the case of 2d in THF/LiClO4 at room temperature, a mixture of the monoadduct 4d and the stereoisomeric bis-adducts cis- and trans-9b was formed. Monoadduct 4d could be transformed to cis- and trans-9b by treatment with 1c in the presence of Rh2(OAc)4 (Scheme 4). Xanthione (2e) and 1c in THF at room temperature reacted only when catalyzed with Rh2(OAc)4, and, in contrast to the previous reactions, the benzoyl-substituted thiirane derivative 5a was the sole product (Scheme 4). Both types of reaction were observed with α-diazo amides 1d,e (Schemes 5-7). It is worth mentioning that formation of 1,3-oxathiole or thiirane is not only dependent on the type of the carbonyl compound 2 but also on the α-diazo amide. In the case of 1d and thioxocyclobutanone 2c in THF at room temperature, the primary cycloadduct 12 was the main product. Heating the mixture to 60°, 1,3-oxathiole 10d as well as the spirocyclic thiirane-carboxamide 11b were formed. Thiirane-carboxamides 11d-g were desulfurized with (Me2N)3P in THF at 60°, yielding the corresponding acrylamide derivatives (Scheme 7). All reactions are rationalized by a mechanism via initial formation of acyl-substituted thiocarbonyl ylides which undergo either a 1,5-dipolar electrocyclization to give 1,3-oxathiole derivatives or a 1,3-dipolar electrocyclization to yield thiiranes. Only in the case of the most reactive 9H-fluorene-9-thione (2f) is the thiocarbonyl ylide trapped by a second molecule of 2f to give 1,3-dithiolane derivatives by a 1,3-dipolar cycloaddition.

Notes: The synthesis of a series of chiral enantiomerically pure C2-symmetric binucleating ligands is reported. Ligands of type 1-4, which consist of a phenolic or heterocyclic unit bridging two chiral dihydrooxazole rings. are readily accessible from chiral amino alcohols. Ligands 5a and 5b are composed of a cyclic urea or thiourea unit, respectively, and two 3,4-dihydro-2H-pyrrole rings containing a stereogenic center next to the N-atom. Compounds of this type are readily assembled from ethane-1,2-diamine and an imidothioic ester derived from pyroglutamic acid. These new ligands, which can coordinate two metals in close proximity to each other, are of interest regarding possible applications in asymmetric catalysis.

Notes: Stability constants have been measured for a series of ligands based on a 2,2′-(pyridine-2,6-diyl)bis[1H-benzimidazole] unit which forms dinuclear double-stranded helical complexes with copper(I). Variation of different structural parameters confirms the importance of the coordinate bond, the stacking interactions, and the weakly bridging pyridine units observed by X-ray crystallography. The stabilities of the complexes depend strongly on the solvent, and in MeCN, which is a good solvent for copper(I), the complexes are less stable and assemble in a stepwise manner. The interconversion of the enantiomers may be followed by 1H-NMR and takes place on a millisecond time scale around room temperature. The trends in lability are similar to those found for the stability of the complexes.

Notes: Oligodeoxyribonucleotides containing 7-deaza-2′-deoxy-8-methylguanosine (m8c7Gd; 2b) were prepared. For this purpose, the phosphonate 3a and the phosphoramidite 3b were synthesized and employed in solidphase oligodeoxyribonucleotide synthesis. The structures and the thermodynamic data of duplex formation of oligodeoxyribonucleotides containing 2b were investigated by temperature-dependent CD and UV spectra and compared with those containing 7-deaza-2′-deoxy-7-methylguanosine (m7c7Gd) or 7-deaza-2′-deoxy-guanosine (c7Gd; 2a). In general, compound 2b reduces the duplex stability. In case of the sequence d(m8c7G-C)4 (18), the B → Z transition was facilitated by the incorporation of 2b. Moreover, a single 7-deaza-8-methylguanine residue present in an oligodeoxyribonucleotide tract of guanine residues destabilizes the dG quadruplex significantly. This destabilization is more pronounced than in the case of 7-deazaguanine or 7-deaza-7-methyl-guanine.

Notes: Absolute rate constants and their Arrhenius parameters are obtained for the addition of a cyclic malonyl radical derived from Meldrum's acid to 20 mono- or 1,1-disubstituted alkenes in (±)-propylene oxide and for the addition of the open-chain di(tert-butyl)malonyl radical to six mono- or 1,1-disubstituted alkenes in 1,1,2-trichloro-1,2,2-trifluoroethane by time-resolved electron spin resonance spectroscopy. At room temperature, the radicals add at the unsubstituted C-atoms with rate constants ranging from 1.1. 105 M-1S-1 (acrolein) to 2.4. 106 M-1S-1 (1,1-diphenylethene). The frequency factors are in the narrow ranges of log (A/M-1S-1) = 8.7 ± 0.1 for the cyclic and log (A/M-1S-1) = 8.2 ± 0.2 for the open-chain malonyl species, whereas the activation energies vary from 12.9 kJ/mol (1,1-diphenylethene) to 21.7 kJ/mol (acrylonitrile). They correlate with the alkene ionization potentials and, more weakly, with the reaction enthalpy. No correlation was found between the activation energies and the alkene electron affinities. Hence, the results confirm and quantify the electrophilic nature of malonyl radicals in addition reactions.

Notes: An asymmetric synthesis of (-)-(4R)-dihydroisomyricoidine (28), a 13-membered amino lactam of type A, was performed by a diastereoselective Michael addition between the spermidine derivative 3 and the commercially available optically active ethyl carboxylate 4, and the cyclization of the resulting ω-amino acid 7 using diethyl phosphorocyanidate ((EtO)2POCN), followed by a Wittig reaction to introduce the (Z)-side chain. Some side reactions are also discussed.

Notes: Natural free carboxylic acids from the hadromerid sponge Diacarnus levii (Kelly-Borges and Vacelet) were esterified to yield the new cyclic norditerpene peroxides ent-muqubilin benzyl ester (= (αR,3S,6R)-α,6-dimethyl-6-[(E)-4-methyl-6-(2,6,6-trimethyl-cyclohex-1-en-1-yl)hex-3-enyl]-1,2-dioxan-3-acetic acid benzyl ester; 6, diacarnoate B methyl ester(= (αS,3R,6R)-α,6-dimethyl-6-{2-(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-3-oxo-2,5,5,8a-tetramethylnaphthalen-1-yl)ethyl}-1,2-dioxan-3-acetic acid methyl ester; 9), and deoxydiacarnoate B benzyl ester (= (αS,3R,6R)-α,6-dimethyl-6-{2-[(4aS,8aS)-3,4,4a,5,6,7,8,8a-octahydro-2,5,5,8a-tetramethyl-1-naphthalenyl]ethyl}-1,2-dioxan-3-acetic acid benzyl ester; 10), which were isolated following extensive chromatography. The relative configuration of the peroxide/α-methylacetate moiety of 6, 9, and 10, was directly determined from their NMR spectra. The absolute configurations of the peroxide/α-methylacetate moiety was deduced from comparative 1H-NMR data of the (S)- and (R)-phenylglycine methyl ester derivatives 7 and 8 as well as 11/13 and 12/14, all obtained from a mixture of the precursors of 3, 6, and 10. The absolute configuration at the carbobicyclic moiety of enone 9 and of 10, is identical, as established by chemical interconversion, 9 and 10 belong to the normal labdane series according to empirical CD rules, applied either directly to 9 or to the parent (+)-sclareolide-derived enone 20. In contrast, molar rotation additivity rules suggest the ent-labdane configuration for 9 and 10. The epidioxides 1-3, 6, and 10 proved active in vitro against the malaria parasite Plasmodium falciparum; especially the previously isolated methyl 3-epinuapapuanoate (2) was active against a chloroquine-resistant strain, and this with a good security index.

Notes: 3-Hydroxy-2-cyanoalk-2-enamides, and 2-cyano-2-(tetrahydrofuran-2-ylidene)- and 2-cyano-2-(tetrahydropyran-2-ylidene)acetamides with N-alkyl and N-aryl substituents have been synthesized in three steps from cyanoacetic acid. Their conformations were investigated by X-ray crystallography and 1H-NMR ROESY spectroscopy at room temperature. The enolic compounds 1-3 adopt an extended conformation stabilized by a strong intramolecular O—H … O=C bond both in the solid state and in (D6)DMSO solution. In contrast, the structure of the cyclic derivatives 5a,b-8a,b is solvent-dependent. In the solid state and in CDCl3 solution, the compounds adopt an extended conformation of type I or III, while, in (D6)DMSO solution, their structures undergo time-dependent (Z)/(E)-isomerization structures (of type II or IV). This observation is compatible with a dipolar transition state of rotation. The kinetics of the isomerization are controlled by the N-substituent, the N-(t-Bu) derivatives 7a and 7b having the highest barrier of rotation around the C=C bond. The whole body of experimental evidence together with the results of molecular-mechanics calculations with I-IV, indicate that, in DMSO, two (E)/(Z)-isomers with two conformations are present, and that they undergo interconversion at room temperature with four different constants. The very fast exchange rates kI,II and kIII,IV in the NMR time-scale might be responsible for the detection of only two isomers.

Notes: A new acylated dimeric secoiridoid glycoside, seemannoside A (2), has been isolated from the aerial parts of Lisianthius seemannii (GRISEB) O. KUNTZE (Gentianaceae). The structure was established by spectroscopic analysis (UV, MS, 1H- and 13C-NMR, and 2D-NMR experiments) and chemical reactions as (E-4′-O-p-coumaroyl)lisianthioside. The structure of the (Z)-isomer (seemannoside B, 3), also present in the plant, was confirmed by LC/UV/1H-NMR analysis. The active principle, 6, responsible for the antifungal activity of the apolar extract against Cladosporium cucumerinum, has been isolated. Its structure has been established by NMR spectroscopy and X-ray crystallographic analysis as a rare type of aglycone monoterpene dimer.

Notes: Asymmetric Diels-Alder reaction of the pentadienoic and hexadienoic acids 2a,b with the chiral chloronitroso derivative 3 gave the primary adducts 4a,b with good-to-excellent enantioselectivity. Subsequent as- or trans-dihydroxylation and hydrogenolytic cleavage of the N—O bond led to the 5-amino-5-deoxypentono-δ-lactams 13a, 14, 15a, and 16 in the D-ribose, L-arabinose, D-xylose, and L-lyxose series, respectively, and to the 5-amino-5,6-dideoxyhexono-δ-lactams 13b and 15b in the D-allose and D-glucose series, respectively.

Notes: The synthesis of the monomeric building block 13 and its constitutional isomer 12 of a new type of DNA analog, distamycin-NA, is presented (Schemes 1 and 2). This building block consists of a uracil base attached to a thiophene core unit via a biaryl-like axis. Next to the biaryl-like axis on the thiophene chromophore, a carboxy and an amino substituent are located allowing for oligomerization via peptide coupling. The proof of constitution and the conformational preferences about the biaryl-like axis were established by means of X-ray analyses of the corresponding nitro derivatives 10 and 11. Thus, the uracil bases are propeller-twisted relative to the thiophene core, and bidentate H-bonds occur between two uracil bases in the crystals. The two amino-acid building blocks 12 and 13 were coupled to give the dimers 15 and 16 using dicyclohexylcarbodiimide (DCC) in THF/LiCl and DMF, respectively. While the dimer 15 showed no atropisomerism on the NMR time scale at room temperature, its isomer 16 occurred as distinct diastereoisomers due to the hindered rotation around its biaryl-like axis. Variable-temperature 1H-NMR experiments allowed to determine a rotational barrier of 19 ± 1 kcal/mol in 16. The experimental data were complemented by AM1 calculations.

Notes: Heating of a mixture of N,N′-(thiocarbonyl)diimidazole (= 1,1′-(carbonothioyl)bis[1H-imidazole]; 1) and 2,5-dihydro-1,3,4-thiadiazole 2a or 2b gave the 1,3-dithiolanes 4a and 4b, respectively, via a regiospecific 1,3-dipolar cycloaddition of the corresponding ‘thiocarbonyl methanides’ 3a,b onto the C=S group of 1 (Schemes 1 and 2). The adamantane derivative 4b was not stable in the presence of 1H-imidazole and during chromatographic workup. The isolated 1,3-dithiole 5 is the product of a base-catalyzed elimination of 1H-imidazole from the initial cycloadduct 4b. The formation of the S,N-acetal 6 can be rationalized by a protonation of the ‘thiocarbonyl ylide’ 3b followed by a nucleophilic addition of 1H-imidazole. With the diazo compounds 8a-e (Scheme 3) 1 underwent a regiospecific 1,3-dipolar cycloaddition to give the corresponding 2,5-dihydro-1,3,4-thiadiazole derivatives 9, which spontaneously eliminated 1H-imidazole to yield (1H-imidazol-1-yl)-1,3,4-thiadiazoles 10. The structures of 10a and 10d were established by X-ray crystallography. In the case of diazodiphenylmethane (8f), the initial cycloadduct 9f decomposed via a ‘twofold extrusion’ of N2 and S to give 1,1′-(2,2-diphenylethenylidene)bis[1H-imidazole] (11; Scheme 3).

Notes: The synthesis of new deoxyribose nucleosides by coupling chloropurines with modified D-ribose derivatives is reported. The methyl 2-deoxy-N-methyl-3-O-(p-toluoyl)-α-D-ribofuranosiduronamide (α-D-8) and the corresponding anomer β-D-8 were synthesized starting from the commercially available 2-deoxy-D-ribose (1) (Scheme 1). Reaction of α-D-8 with the silylated derivative of 2,6-dichloro-9H-purine (9) afforded regioselectively the N9-(2′-deoxyribonucleoside) 10 as anomeric mixture (Scheme 2), whereas β-D-8 did not react. Glycosylation of 9 or of 6-chloro-9H-purine (17) with 1,2-di-O-acetyl-3-deoxy-N-methyl-β-D-ribofuranuronamide (13) yielded only the protected β-D-anomers 14 and 18, respectively (Scheme 3). Subsequent deacetylation and dechlorination afforded the desired nucleosides β-D-11, β-D-12,15, and 16. The 3′-deoxy-2-chloroadenosine derivative 15 showed the highest affinity and selectivity for adenotin binding site vs. A1 and A2A adenosine receptor subtypes.

Notes: (S)-5,5,5,5′,5′,5′-Hexafluoroleucine ((S)-13) of 81 % ee is prepared from hexafluoroacetone (l) and ethyl bromopyruvate (= ethyl 2-oxopropanoate) in 7 steps with an overall yield of 18% (Schemes 1 and 2). Key step in this sequence is the highly enantioselective reduction of the carbonyl group in α-keto ester 4 either by bakers' yeast (91 % ee) or by ‘catecholborane’ 6 utilizing an oxazaborolidine catalyst, yielding hydroxy ester (R)-5 with 99% ee. The absolute configuration was determined by X-ray analysis of the HCl adduct (S,R)-9b of (2S)-N-[(R)- l-phenylethyl]-5,5,5,5′,5′,5′-hexafluoroleucine ethyl ester.

Notes: N-Fmoc-Protected (Fmoc = (9H-fluoren-9-ylmethoxy)carbonyl) β-amino acids are required for an efficient synthesis of β-oligopeptides on solid support. Enantiomerically pure Fmoc-β3-amino acids β3: side chain and NH2 at C(3)(= C(β)) were prepared from Fmoc-protected (S)- and (R)-α-amino acids with aliphatic, aromatic, and functionalized side chains, using the standard or an optimized Arndt-Eistert reaction sequence. Fmoc-β2- Amino acids (β2 side chain at C(2), NH2 at C(3)(= C(β))) configuration bearing the side chain of Ala, Val, Leu, and Phe were synthesized via the Evans' chiral auxiliary methodology. The target β3-heptapeptides 5-8, a β3- pentadecapeptide 9 and a β2-heptapeptide 10 were synthesized on a manual solid-phase synthesis apparatus using conventional solid-phase peptide synthesis procedures (Scheme 3). In the case of β3-peptides, two methods were used to anchor the first β-amino acid: esterification of the ortho-chlorotrityl chloride resin with the first Fmoc-β-amino acid 2 (Method I, Scheme 2) or acylation of the 4-(benzyloxy)benzyl alcohol resin (Wang resin) with the ketene intermediates from the Wolff rearrangement of amino-acid-derived diazo ketone 1 (Method II, Scheme 2). The former technique provided better results, as exemplified by the synthesis of the heptapeptides 5 and 6 (Table 2). The intermediate from the Wolff rearrangement of diazo ketones 1 was also used for sequential peptide-bond formation on solid support (synthesis of the tetrapeptides 11 and 12). The CD spectra of the β2- and β3-peptides 5, 9, and 10 show the typical pattern previously assigned to an (M) 31 helical secondary structure (Fig.). The most intense CD absorption was observed with the pentadecapeptide 9 (strong broad negative Cotton effect at ca. 213 nm); compared to the analogous heptapeptide 5, this corresponds to a 2.5 fold increase in the molar ellipticity per residue!

Notes: On irradiation (350 nm) in the presence of excess 2,3-dimethylbut-2-ene, the newly synthesized title compound 5 affords as main products the unexpected cyclopropylpyrrolidine 10 (50%) and the spiro-oxetane 9 (25%).

Notes: Among seventeen different Lewis acids, TiCl4 was found to be the best catalyst for the [4 + 2] cycloaddition of cyclopentadiene to N,N′-fumaroylbis[(2R)-bornane-10,2-sultam] ((-)-1). Independently of the TiCl4 molar concentration, almost constant and complete (98-89% d.e.) diastereofacial π-selection was achieved in the Diels-Alder addition of (-)-1 to cyclopentadiene, cyclohexadiene, isoprene, and 2,3-dimethylbuta-1,3-diene.

Notes: A new facile synthesis of N,S- and N,Se-acetals starting from aldehydes and primary amines is presented (Schemes 3-5). These acetals are used as precursors for stereoselective radical deuteration and allylation reactions (Schemes 6 and 7, Tables 1 and 2). The stereochemical outcome of the reactions depends on the radical trap and the substituents at the N-atom. Deuterations give always anti products with moderate to high selectivities. The allylation reactions give either syn or anti products with low to moderate selectivities. The observed stereoselectivities can be explained with a model based on minimization of A1,3 strain and are controlled by steric and stereoelectronic effects.

Notes: Based on O-methylasparvenone (1), a N-free 5HT2C antagonist with moderate affinity (pKi = 6.7), derivatives bearing dimethylamino (7), (dimethylamino)methyl (17, 18, 21, and 22), and aminomethyl substituents (26) in place of the benzylic OH group of 1 as well as pyrrolidine- (33) and piperidine-fused derivatives (29, 43, and 45) were synthesized. In contrast to the lead structure 1, these new ligands were active in vivo in the rat. The tricycles 33 and 45 display high affinities for the 5HT2C receptor (pKi = 8).

Notes: Thermal reactions of 1,2,3-trisubstituted aziridines 1 with 1,3-thiazole-5(4H)-thiones 6 in toluene yielded, in general, a mixture of two diastereoisomeric spirocyclic [2+3] cycloadducts. The formation of these products can be explained by a stereoselective electrocyclic ring opening of 1 to give an azomethine ylide 2 as the reactive intermediate, which is trapped immediately by 6 via a stereoselective 1,3-dipolar cycloaddition. Only in the case of trans-dimethyl 1-(4-methoxyphenyl)aziridine-2,3-dicarboxylate (trans-1a), four diastereoisomeric cycloadducts were formed (Scheme 4). This result is rationalized by an isomerization of the intermediate azomethine ylide cis-2a to trans -2a.

Notes: Due to their small mass, adjacent protons (or H-atoms) of molecular systems may exhibit quantum entanglement (or quantum correlations), even at ambient conditions. The considerable thermal disturbance and/or manybody interactions of condensed matter and the associated decoherence effect, however, cause this protonic entanglement to be restricted in space and time. Some aspects of entanglement and decoherence are mentioned. Extending our previous theoretical work, in the present paper the focus is on the possible existence of entangled protons belonging to the H-bonds of adjacent base pairs of B-type DNA. Based on the ‘working hypothesis’ that this effect does really exist, the most probable ‘positions’ for the appearance of protonic entanglement in DNA sequences are qualitatively determined. Furthermore, these ‘positions’ appear to correspond uniquely to dimers of adjacent base pairs of DNA. As a consequence, one can straightforwardly search for an enhanced appearance of such entangled H-bonds in DNA sequences of living organisms, using the existing DNA databases. A quantitative analysis of protein-coding DNA sequences of various organisms has been performed, the results of which provide strong evidence for the existence of the considered effect. The most striking finding may be summarized as follows: Quantum entanglement appears preferably between the third base of a codon and the first base of the following one. Quantitative estimates of this and further obtained results are presented. It is also shown that quantum-chemical considerations of stacking energies cannot account for the results. The new findings provide first evidence for the biological significance of entangled H-bonds.

Notes: The title compounds D-10 and L-10 were prepared from 1 in eight steps and in a combined overall yield of 41-49%.

Notes: The reaction of N,N'-dimethyl-2-nitroethene-1,1-diamine (8) with α,ß-unsaturated acyl isothiocyanates 9 affords 3,3-diamino-2-nitroacrylthioamides 10 (Scheme 2) in moderate-to-good yields. Cyclization of 10 under acidic conditions gives 1,3-thiazin-4-one derivatives of type 11. Oxidative cyclization of 10 with diethyl azodicaboxylate leads to 4-nitro-1,2-thiazol-5(2H)-imine derivatives 12.

Notes: The CH2Cl2 extract of Monotes engleri Gilg. (Dipterocarpaceae) showed antifungal activity against the yeast Candida albicans in our bioautographic TLC assays. After a first fractionation of the crude extract, the bioactivity was located in one of the fractions. To perform an efficient targeted isolation of the active compounds, LC/UV/MS and LC/UV/NMR analyses of the crude extract and the active fraction were performed. LC/UV/, LC/MS, and LC/NMR data (1D and 2D) allowed the identification of 1 as (2S)-2,3-dihydro-5,7-dihydroxy-{3-hydroxy-4-[(3-methylbut-2-enyl) oxy]phenyl}-4H-1-benzopyran-4-one, a new prenylated flavanone, named monoteson A. Subsequent isolation of 1 has permitted the determination of its absolute configuration on the basis of CD measurements. Theree other prenylated flavanoes 2-4 were isolated from the same extract. Compound 3 was identified as 2- (3, 5-dihydroxyphenyl) -2,3-dihydro-5, 7-dihydroxy-6, 8-bis (3-methylbut-2-enyl)-4 H-1-benzopyran-4-one, another new natural product, named monotesone B. The structures of 2 and 4 were established as selinone and lonchocarpol A, respectively. The antifungal activity against Candida albicans was determined for all compounds.

Notes: The disubstituted clusters[Ir4(CO)10(μ2-L—L)] with one edge-bridging ligand have a ground-state geometry with all COs terminal (L—L = (MeS)2CHMe, cluster 1) or with three edge-bridging COs (L—L = (Ph2P)2CHMe, cluste 2; L—L =Ph2P(CH2)3PPh2, cluster 3) in the solid state and in solution. A comparative 13C-NMR study of 1-3 shows that their respective ground-state geometries are merely relative minima of energy in the same kinetic profile of successive fluxional processes consisting of a merry-go-round of six COs about a unique trangular face and the rotation of terminal COs about one Ir-atom. The factors affecting the activation energy of the merry-go-round result from the relative bites of the bidentate ligands in the ground-state geometry, as shown by a comparison of the molecular structures of 2 and 3.

Notes: The kinetics of the reaction between pyridoxal 5′-phosphate (PLP) with carbidopa, hydralazine, and isoniazid, in aqueous solution at variable pH and constant ionic strength of 0.1M was studied spectrophotometrically. The rate constants of formation and hydrolysis of the resulting Schiff base, and its stability were determined in a wide range of pH. A comparison is made of the formation rate constants with those of PLP with hydrazine. The reactivity shows the sequence isoniazid 〉 hydrazine 〉 carbidopa 〉 hydralazine in the whole range of pH studied. The Schiff bases studied are more stable than those formed by PLP and hexylamine and as stable as those described for the reactions of PLP with poly(L-lysine) or copolypeptides containing L-lysine.

Notes: The coordination behavior of chiral binucleating ligands of type 1-4 with various transition metals has been investigated. 1H-NMR Titration experiments with zinc(II) salts gave detailed structural information about the structure of the resulting zinc complexes. Ligand 1 forms an unusual C3-symmetric dinuclear zinc complex [Zn2CIL3] (8a) which was characterized by X-ray crystallography. Treatment of complex 8a with various carboxylic acids resulted in ligand-exchange reactions. With ligand 2, a hydroxo-bridged dinuclear copper complex 15 was synthesized and its structure elucidated by X-ray analysis. Solution studies UV and 1H-NMR spectroscopy of the reaction of ligand 3 with ZnII and NII salts revealed the formation of dimeric species of the type [M2X4L2]. Ligand 4 formed well-defined dinuclear complexes with NiII and CuII salts of which the corresponding NiII complex [Ni2(AcO)2(ClO4)2L] (22a) was characterized by crystal-structure analysis.

Notes: Why Pentose- and Not Hexose-Nucleic Acids? Purine-Purine Pairing in homo-DNA: Guanine,Isoguanine, 2,6-Diaminopurine, and XanthineThis paper concludes the series of reports in this journal [1-4] on the chemistry of homo-DNA, the constitutionally simplifie dmodel system of hexopyranosyl-(6′ → 4′)-oligonucleotide systems stidued in our laboratory as potentially natural-nucleic-acid alternatives in the context of a chemical aetiology of nucleic-acid structure. The report describes the synthesis and pairing properties of homo-DNA oligonucleotides which contain as nucleobases exclusively purines, and gives, together with part III of the series [3], a survey of what we know today about purine-purine pairingin homo-DNA. In addition, the paper discusses those aspects of the chemistry of homo-DNA which, we think, influence the way how some of the structural features of DNA (and RNA) are to be interpreted on a qualitative level.Purine-purine pairing occurs in the homo-DNA domain in great variety. Most prominent is a novel tridentate Watson-Crick pair between guanine and isoguanine, as well as one between 2,6-diaminopurine and xanthinone, both giving rise to very stable duplexes containing the all-purine strands in antiparallel orientation. For the guanine-isoguanine pair, constitutional assignment is based on temperature-dependent UV and CD spectroscopy of various guanine- and isoguanine-containg duplexes in comparison with duplexes known to be paired in the reverse guanine is replaced by 7-carbauguanine. Isoguanine and 2,6-diaminopurine also have the capability of self-pariring in the reverse-Hoogsteen mode, as previously observed for adenine and guanine [3]. In this type of pairing, the interchangeably. Fig. 36 provides an overall survey of the relative strength of pairing in all possible purine-purine combinations.Watson-Crick pairing of isoguanine with guanine demands the former to participate in its 3H-tautomeric form; hitherto this specific tautomer had not been considered in the pairing chemistry of isoguanine. Whereas (cumulative) purine-purine pairing in DNA (reverse-Hoogsten or Hoogsteen) seems to occur in triplexes and tetrapalexes only, its occurrence in duplexes in a characteristic feature of homo-DNA chemistry. The occurrence of purine-purine Watson-Crick base pairs is probably a consequence of homo-DNA's quasi-linear ladder structure [1][4]. In a double helix, the distance between the two sugar C-atoms, on which a base pair is anchored, is expected to be constrained by the dimensions of the helix; in a linear duplex, however, there would be no restrictions with regard to base-pair length. Homo-DNA's ladder-like model also allows one to recognize one of the reasons why nucleic-acid duplexes prefer to pair in antiparallel, rather than parallel strand orientation: in homo-DNA duplexes, (averaged) backbone and base pair axes are strongly inclined toward one another [4]; the stronger this inclination, the higher the preference for antiparallel strand orientation is expected to be (Fig. 16).In retrospect, homo-DNA turns out to be one of the first artificial oligonucleotide systems (cf. Footnote 65) to demonstrate in a comprehensive way that informational base pairing involving purines and pyrimidines is not a capability unique to ribofuranosyl systems. Stability and helical shape of pairing complexes are not necessary conditions of one another; it is the potential for extensive conformational cooperativity of hte backbone structure with respect to the constellational demands of base pairing and base stacking that determines whether or nor a given type of base-carrying backbone structure is an informational pairing system. From the viewpoint of the chemical aetiology of nucleic-acid structure, which inspired our investigations on hexopyranosyl-(6′ → 4′)-oligonucleotide systems in the first place, the work on homo-DNA is only an extensive model study, because homo-DNA is not to be considered a potential natural-nucleic-acid altenratie. In retrospect, it seems fortunate that the model study was carried out, because without it we could hardly have comprehended the pairing behavior of the proper nucleic-acid alternatives which we have studied later and which will be discussed in Part VI of this series.The English footnotes to Fig. 1-49 provide an extension of this summary.

Notes: ‘Fully chiral’ dendrimers, containing a stereogenic center at each and every branching point, have been prepared using a chiral core triol with aromatic elongating units (cf. 27) and chiral branch diols (cf. 8, 12, and 24) as building blocks. The biggest dendrimer prepared is of the 4th generation (33: 46 building blocks, 93 stereogenic centers, 1028 possible stereoisomers), and has been obtained by a convergent growth approach in 32 steps starting from the biopolymer poly[(R)-3-hydroxybutanoic acid] (P(3-HB)). All compounds were shown to be monodisperse by MALDI-TOF mass spectrometry. Spin-lattice relaxation-time (T1) measurements and size-exclusion chromatography show typical features of structurally related achiral dendrimers. The influence of the chiral building blocks on the shape of the whole dendrimer has been investigated by chiroptical measurements: the specific rotation can be considered as average of all chiroptical properties of its constituent chiral units, independent of the solvent, the concentration, and the temperature. On the other hand, regularity in the circular dichroism (CD) spectra is completely lost with variation of the solvent (cf. Fig. 13).

Notes: The first steps, believed to be involved in the highly enantioselective copolymerization of styrene and carbon monoxide to poly[1-oxo-2-phenylpropane-1,3-diyl] with phosphinodihydrooxazole-palladium(II) complexes, were investigated. The insertion of carbon monoxide into [Pd(Me)(P^N)(solvent)] TfO (P^N = (S)-2-[2-(5H-benzo[b]phosphindol-5-yl)phenyl]4-benzyl-4,5-dihydrooxazole (1)) and of styrene into [Pd(Me)(P^N)(solvent)] TfO were highly regioselective (alkyl and acyl substituents trans to N); moreover, the olefin insertion took place with essentially complete enantioface discrimination.

Notes: The [4 + 2] cycloadduct 17 of 2,3-dimethylidene-1,2,3,4-tetrahydro-1,4-methanonaphthalene and 4-phenyl-4H-1,2,4-triazole-3,5-dione (PTAD) was subjected to a triplet-sensitized di-π-methane rearrangement. Hydrolysis of the resulting urazol 18 gave the hydrocarbon 7. Hydrolysis of 18 at lower base concentrations led to isomeric stable semicarbazides 24 and 25, which were submitted NiO2 or MnO2 oxidation, to give the target compound 7, and oxidation products 26 and 27.

Notes: The difference between the strong inhibition of retaining β-glucosidases by the tetrazole 1 and the weak inhibition by the triazole 3 has been explained by the protonation by the enzymic catalytic acid of N(3) of 1, replaced by CH in 3. One also expects a contribution to the inhibition from the charge-dipole interaction between the enzymic catalytic nucleophile and the azole ring. The extent of this contribution was estimated from the calculated, distance-dependent heats of formation of the acetate-azole complexes. The calculations were validated by comparison of the charge-dipole interaction between phosphate and the inhibitors 1 and 3 in the glycogen phosphorylase b (GPb)-azole-phosphate complexes, as derived from differences in the Ki values for 1 and 3, while the structural invariance of the complexes was demonstrated by X-ray analysis. The difference between the charge-dipole interactions of (dihydrogen) phosphate and 1 or 3 as derived from Δ Ki is 1.1 kcal mol-1, while the calculated difference is 1.3 kcal mol-1. The calculated difference for the interaction of 1 or 3 with acetate, representing the catalytic nucleophile in β-glycosidases, is 2.0 kcal mol-1, while the differences of the binding energies as derived from the Ki values for the inhibition by 1 or 3 of different β-glycosidases range from 2.4 to 5.3 5 kcal mol-1. The calculated difference for 1 and the imidazole 6 is 2.5 kcal mol-1 in favour of 1, whereas the Ki-derived difference is 3.7 kcal mol-1 in favour of 6, equal to the calculated difference between 1 and the protonated imidazole 6. Thus, protonation by the catalytic acid and the charge-dipole interaction with the catalytic nucleophile contribute cooperatively to the binding of inhibitors possessing a trigonal anomeric centre bonded to a heteroatom.

Notes: Described are the preparation of nanocrystals and the synthesis of molecules that may be covalently or noncovalently assembled in solution to yield heterosupermolecules possessing a well-defined heterosupramolecular function. Also described are preparative and synthetic methods that yield organized assemblies of heterosupermolecules possessing an addressable heterosupramolecular function. Finally, the development of these synthetic strategies to permit the covalent and noncovalent assembly and organization of a wide range of condensed phase and molecular components is outlined.

Notes: For a comparison with the corresponding α- and β-hexapeptides H-(Val-Ala-Leu)2-OH (A) and H-(β-HVal-β-HAla-β-HLeu)2-OH (B), we have now prepared the corresponding γ-hexapeptide 1 built from the homochirally similar (S)-4-aminobutanoic acid, (R)-4-amino-5-methylhexanoic acid, and (R)-4-amino-6-methylheptanoic acid. The precursors were prepared either by double Arndt-Eistert homologation of the protected amino acids Boc-Val-OH, Boc-Ala-OH, and Boc-Leu-OH (Schemes 1 and 2), or by the superior route involving olefination/hydrogenation of the corresponding aldehydes (Boc-valinal, Boc-alaninal, and Boc-leucinal; Scheme 3). Conventional peptide-coupling methodology (EDC/HOBt) furnished the γ-hexapeptide 1 (through the intermediate γ-di- and γ-tripeptide derivatives 9-11). Analysis of NMR measurements in (D5)pyridine and CD3OH solution (COSY, TOCSY, HSQC, HMBC, ROESY) reveals that the γ-hexapeptide 1 adopts a right-handed helical structure ((P)-2.61 helix of ca. 5-Å pitch, containing 14-membered H-bonded rings) which is to be compared with the left-handed helix of the corresponding β-peptide B ((M)-31 helix of 5-Å pitch, 14-membered H-bonded rings) and with the familiar right-handed, so-called α-helix of α-peptides ((P)-3.61 helix of 5.4-Å pitch, 13-membered rings). Like the helix sense, the helix dipole reverses when going from α-, (N + → C) to β-(C + → N) to γ-peptides (N + → C). The surprising difference between the natural α-, and the analogous β- and γ-peptides is that the helix stability increases upon homologation of the residues.

Notes: 7-O-Substituted analogs of deaminodeoxycolchinol thiomethyl ether were synthesized and evaluated for their inhibitory effects on tubulin polymerization in vitro. Ketone 9, a key compound in this study, was derived from thiocolchicone 6 by reaction with aniline. Reaction of compound 6 with MeNH2 or BuNH2 gave tetracyclic lactams 7 and 8, respectively. Optically active alcohols 11a and 11b were obtained from racemic 11 by chemical resolution including a separation of the comphanate diastereoisomers 12a and 12b, followed by basic hydrolysis. The (aR,7R)-configuration of 12b was verified by X-ray crystallographic analysis. Almost all racemic and optically active 7-O-acyl or 7-O-aroyl compounds had strong inhibitory effects on the tubulin polymerization reaction, with IC50 values from 1.7 to 5.1 μM. A few agents, such as the lactams 7 and 8, the camphanates 12a and 12b, the cyclohexanecarboxylates 19a and 19b, and, most notably, the (7S)-benzoate 15a, had negligible effects on polymerization, yielding IC50 values greater than 40μM. Ketone 9 showed strong inhibition of tubulin polymerization comparable to that of thiocolchicone (6). Optically active alcohol 11a and acyl esters 13a and 14a with a (7S)-configuration were more active than the (7R)-esters 13b and 14b. However, the esters 15a-17a with a (7S)-configuration were less active than the (7R)-isomers 15b-17b, in which the (7R)-benzoate 15b was at least 15-fold more inhibitory than the (7S)-isomer 15a. For the most part, the agents causing strongest inhibition of polymerization also caused the greatest inhibition of [3H]colchicine binding. NMR and optical rotatory data indicate that, in polar solvents, the equilibrium in esters with a 7-O-aroyl substituent, i.e., 15a,b, 16a,b, and 17a,b, is reversed from (aS) to (aR) or from (aR) to (aS), as compared to nonpolar solvents.

Notes: As a continuation of our previous studies on the synthesis and antiplatelet activity of quinolin-2(1H)-ones with an α-methylidene-γ-butyrolactone substituted at O(8), the O(6)- and N(1)-substituted isomers were synthesized and evaluated for antiplatelet activity against thrombin (Thr)-, arachidonic acid (AA)-, collagen (Col)-, and platelet-activating-factor (PAF)-induced aggregation in washed rabbit platelets. These compounds were synthesized from 6-hydroxyquinolin-2(1H)-one via alkylation and Reformatsky-type condensation (Schemes 1 and 2). All of them were found to inhibit the platelet aggregation perfectly which was induced by AA and Col. 6-Substituted isomers 5b-g exhibited very strong inhibitory activities against AA- and PAF- induced aggregation and are approximately ten times more potent than their 8-substituted counterparts. However, the 1-substituted (11a and 11b) and the 1,6-disubstituted (6) counterparts were relatively inactive. Their effects on the Ca2+-dependent vasoconstriction induced by high K+, and the phasic and tonic vasoconstrictions induced by norepinephrine (NE) in rat aorta were also evaluated. Except 5g, all of them were found to have significant inhibitory activity on the NE-induced phasic and tonic vasoconstrictions. Compounds 6 and 11b also exhibited strong inhibitory activity on high-K+ medium, Ca2+-induced vasoconstriction.

Notes: The photolysis of N-alkylpyridinium halides 9a-e in alkaline H2O gave 6-azabicyclo[3.1.0]hexenol derivatives 10a-e. N-Substituents bearing ether, acetal, and alcohol functions were found to do not adversely influence the photochemical reaction course. The free OH groups of the N-(3-hydroxypropyl) derivative 10d were protected by benzoylation. The ensuing dibenzoate 14 underwent stereocontrolled opening of the aziridine ring on reaction with MeSH/BF3 to give a thioether 15. With benzoic acid in CHCI3, 10d gave the 4-hydroxy-5-aminocyclopent-2-enyl benzoate 11. The meso-2-aminocyclopent-4-ene-1,3-diol 12 was obtained by hydrolysis of 11. On reaction with Boc2O and NaI, the aziridine ring of 14 was converted to a bicyclic compound 17. Hydrolysis of 17 provided the trans-1,3-diol 18, the epimer of 12. Face-selective dihydroxylation of Boc-protected 12 gave a meso-aminocyclopentanetetrol 23 which was characterized upon peracetylation. Dihydroxylation of 15 provided a racemic analogue of epi-mannostatin A (26).

Notes: An alternative synthesis of enantiomerically pure SDZ 220-881 (1a) and SDZ EAB 515 (1b) starting from L-Z-tyrosine is described.

Notes: Bicyclic thiohydantoins were synthesized in a stereoselective manner by reacting (2R)/(2S)-diastereoisomer mixtures of 1,3-thiazolidine-2,4-dicarboxylic acids or their dimethyl diesters with PhNCS. 5,5-Dimethyl-1,3-thiazolidine-2,4-dicarboxylic acid with PhNCS led to a cyclization involving the C=O group at the C(2) center of the thiazolidine ring, while the acid's dimethyl diester gave cyclization involving the C=O group at C(4). In contrast, reactions involving unsubstituted 1,3-thiazolidine-2,4-dicarboxylic acid or its dimethyl diester led to thiohydantoins in which the ring closure had taken place only with the COO group at C(4). Independently of the direction of the ring closure, all reactions produce exclusively products with the (R)-configuration at C(2). The configurational assignments were based on 1H- and 13C-NMR studies, and confirmed by X-ray crystallographic analyses.

Notes: The new, axially chiral bis(4,5-dihydrooxazoles) 4 have been synthesized in a straightforward manner, starting from the substituted, racemic 1,1′-biphenyl-2,2′-dicarboxylic acids 1 and optically active amino alcohols 2. The adducts were resolved by medium-performance liquid chromatography (MPLC; see Scheme 1). Formation of Cu1 complexes of 4 was followed by 1H-NMR spectroscopy. The catalytic behavior of these complexes has been investigated by asymmetric cyclopropanation of styrene with ethyl diazoacetate. Beside the influence of steric factors, a significant electronic effect on asymmetric induction could also be observed (see Scheme 2 and Table).

Notes: The synthesis of the enantiomerically pure, bridgehead-functionalized bicyclo[3.2.1]octanes 11 and 16, containing a conformationally fixed trihydroxypropyl (aminodihydroxypropyl) unit, as well as the X-ray structure of 11 are described. These compounds are of interest as sugar surrogates in the preparation of DNA analogs. Compounds 11 and 16 became available in 10 and 12 steps, respectively, and in an overall yield of 11 and 4% from D-arabinose via a highly stereoselective pinacol coupling as the key step.

Notes: New derivatives of campholenaldehyde (= 2-(2,2,3-trimethylcyclopent-3-enyl)ethanal bearing two cyclopropane moieties were synthesized, and the structure of the stereoisomer responsible for its exceptionally strong, diffusive, and natural sandalwood-oil scent, ((1S,2S)-1-methyl-2-{[1S,3R,5R)-1,2,2-trimethylbicyclo[3.1.0]hex-3-yl]methyl}cyclopropyl)methanol (13a), was elucidated.

Notes: Titanium-dioxide surfaces have been glycosylated with the benzyl-, 4-fluorobenzyl-, and acetyl-protected diazirines 1-3. The modified TiO2 surfaces were characterized by contact-angle measurement, X-ray photoelectron spectroscopy (XPES), and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The main by-products of the glucosidation (mostly azines and trehaloses) were identified. Their physisorption slightly reduces the efficiency of the glucosidation by 1 mM solution of 1 or 2 in CH2Cl2, but this influence is neutralized by repeating the glucosidation, or by using a 100 mM solution of the diazirines. The immobilized, acetylated glucosyl moieties were deacetylated in situ. Calculations based on the XPES peaks of Ti 2p and F 1s for the TiO2 surface modified with 2 indicated 1.5 ± 0.9 immobilized glucosyl moieties per nm2.

Notes: A Chemotaxonomic survey for biologically active compounds from Malaysian Calophyllum species led to the findings of the four new benzoylcoumarins 1a, 2, 3, and 4a (including the unusual prenylated 6-benzoylcoumann 1a), two uncommon coumarins 5 and 6a with a pyran-4-one moiety fused at C(6) and C(7), and compounds 7a, 9, and 10, all isolated from the bark of C. teysmannii var. inophylloide. Their structures were determined by spectroscopic analysis and chemical transformations. X-Ray crystal-structure determination of 2 provided information on the conformational preferences of substituents in this class of coumarins. The syntheses of the cytotoxic calanone (7a) and of some related coumarins are described.

Notes: The heme-thiolate protein chloroperoxidase (CPO) catalyzes the chlorination of activated C—H bonds. A reaction mechanism is proposed for this enzymatic transformation (Scheme 1), and a new iron(III) porphyrinate complex 13 is synthesized containing pentafluorophenyl groups at two meso-positions and a thiophenolato ligand coordinating to the Fe-atom (Schemes 2 and 3). Due to the presence of the electron-withdrawing substituents, the catalyst 13 is appreciably resistant to oxidants (HOCl) and chlorinates, e.g., monochlorodimedone (5), with turnover numbers up to 1530. The redox potential of 13, E0 = - 134 mV, and the Soret band (λmax 448 nm) of the CO adduct of the reduced state of 13 are close to the corresponding values of the enzyme CPO.

Notes: The chemical synthesis of 2′-amino-2′-deoxyribonucleosides of uracil, cytosine, adenine, and guanine, and their conversion into suitably protected 3′-phosphoramidite building blocks 35-40 for oligonucleotide synthesis are described. The aglycone and the 2′-amino functions were protected using the 2-(4-nitrophenyl)ethoxycarbonyl (npeoc) group. The synthesis of the 3′-O-succinyl (3′-O-(3-carboxypropanoyl))-substituted starting nucleoside 41 is described and its behavior examined in solution and on solid phase with regard to an anticipated migration during 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) deprotection. Oligonucleotides were prepared using the new building blocks, and their hybridization properties were studied by UV-melting techniques.

Notes: Chiral supermolecules may be obtained from suitable achiral molecular constituents associated through a dissymmetrizing interaction mode. This is the case for the supermolecules I-IV formed by hydrogen-bonding association between the achiral complementary components 1a,b and 2a,b,c. The crystal structures of the supermolecular pairs I-III and of the homochiral aggregate of two ternary supermolecules IV have been determined. The structural data are discussed.

Notes: Various bifunctional amino-protecting groups such as the phthaloyl, succinyl, and glutaryl group were investigated as potential linker molecules for attachment to solid-support materials. Pentane-1,3,5-tricarboxylic acid 1,3-anhydride (16) offered the best properties and reacted with the amino groups of differently sugar-protected adenosine (see 20 and 22), cytidine (see 29), and guanosine derivatives (see 32) to the corresponding 2-(2-carboxyethyl)glutaryl derivatives 23, 24, 30, and 33. The usefulness of the new linker-type molecules was demonstrated by the solid-support synthesis of the potentially antivirally active 3′-deoxyadenylyl-(2′-5′)-2′-adenylic acid 2′-{2-[(adenin-9-yl)methoxy]ethyl} ester (38) starting from the 2′-end with N6,N6-[2-(2-carboxyethyl)glutaryl]-9-{{2-[(4,4′-dimethoxytrityl)ethoxy]methyl}adenine (12).

Notes: An efficient stereocontrolled synthesis of (S)-N-Cbz-serine (Cbz = benzyloxycarbonyl; 12) and of its (R)-enantiomer is reported. Kinetic resolution of the easily available racemic 3-(hydroxymethyl)-1,4-benzodiazepin-2-ones is performed in the key step via acetylation by the immobilized Mucor miehei lipase (Lipozyme IM) at 60°. This method is characterized by high enantiomer purity (ee's ges; 99%) of the intermediary alcohols (+)-8 and (+)-9 and acetates (-)-10 and (-)-11, as well as of the final products (S)- and (R)-N-Cbz-serine, simple recycling of the biocatalyst, complete recovery of 2-aminobenzophenones (3 and 4) and their recycling into production of 1,4-benzodiazepines, and possibility to selectively racemize ‘wrong’ enantiomers of the alcohols 8 and 9 in the presence of Amberlite CG 400.

Notes: The fate of an insect juvenile hormone analog applied to the insect body of the flesh fly (Sarcophaga bullata) or the tsetse fly (Glossina palpalis), respectively, was studied using three different radiolabeled positions in the parent biologically active compound 1. Several metabolites were found and analyzed. A mechanism of degradation of the applied molecule was designed using a combination of several radioanalytical methods. A unique monitoring of the applied compound and its metabolites was provided, based on the different radiolabeling of the structure (cf. 1a-1c), and established their fate in an insect body during a 10-day experiment. A 14C and 3H radiolabeling, respectively, was employed to synthesize three different radiolabeled forms 1a-1c derived from the parent non-labeled 1. A combination of three different ways of radiolabeling resulted in an advantage in tracing the metabolic pathway of degradation of the employed compound 1 in its radiolabeled forms 1a-1c.

Notes: Previous work has indicated orbital-symmetry effects upon forward electron transfer in bimolecular systems, with magnitude similar to that encountered in rigid monomolecular systems. The present work, which employs back electron transfer, supports and extends these earlier findings.

Notes: According to ab-initio calculations, the CF…HO H-bond in 1,3-diaxial 3-fluorocyclohexanol is characterized by d(F…H) = 2.08 Å, and ∠ (F…H—O) = 138°, and by ΔE between 1.2 and 4.1 kcal/mol, depending upon the reference system. Relative to the OH stretching frequency of axial cyclohexanol, the OH stretching frequency of 1,3-diaxial 3-fluorocyclohexanol is shifted by Δω = 7 cm-1. The rigid fluoro diols D-4 and L-4 were prepared from tetrahydroxy-p-benzoquinone in 11 steps and 1% overall yield. The IR spectrum of 4 in CCl4 soln. is characterized by Δν = 7 cm-1 for the axial and Δν = 44 cm-1 for the equatorial OH group. A relatively strong intramolecular CF…HO bond of 4 in CCl4 is evidenced by the large through-space coupling 5J(F,HO) of 9.3 Hz. Nevertheless, this FHO bond is disrupted in ethereal solvents, while the bifurcated O…HO bond subsists. In CCl4, the carbene generated from the glucosylidene-derived diazirine 5 reacted more rapidly with the axial OH group of D-4 and L-4 than with the equatorial one. This regioselectivity is in keeping with the weaker H-bond of the axial OH group. The regioselectivity is lower in ethers, but its solvent dependence does not parallel solvent basicity. This is not satisfactorily explained by the differential interaction of the ether solvents with the axial and equatorial OH groups, as evidenced by the solvent dependence of their chemical shift, but must also reflect the different interaction of the solvents with the carbene derived from 5, leading to ylides. The lower solvent dependence of the anomeric selectivity for the glycosidation of the equatorial OH group is a consequence of the coordination of the intermediate oxycarbenium ion with O—C(1) and O—C(3) rather than with the solvent. Under conditions of competitive glycosylation in CCl4, the fluoro alcohol D-22 reacted more slowly than the alcohol L-24, evidencing the intramolecular F…HO H-bond.

Notes: Khusimone (1), one of the main odor-donating compounds of vetiver oil, is subject of the following study on structure/odor relationship. The omittance of the methano bridge of the tricyclic khusimone should lead to the bicyclic partial structure (-)-2. Unexpectedly, (-)-2 could not be obtained since epimerization favored (-)-16. The stereochemical key step of the synthesis of the hydrazulene nucleus is based on a highly diastereoselective conjugate addition to a chiral oxocyclopent-1-ene-1-carboxylate.

Notes: A convenient preparation of (1R,2S,3R,4S)-3-(neopentyloxy)isoborneol (= (1R,2S,3R,4S)-3-(2,2-dimethyl-propoxy)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol; 1a), a valuable chiral auxiliary, is described. The synthesis involves six steps starting from the readily available camphorquinone (5) and gives 1a in 48% overall yield. The key step is the chemoselective hydrolysis of the less hindered 1,3-dioxolane moiety in the camphorquinone di-acetal 4.

Notes: A novel general synthesis of 2,4,5-tri- and 2,4,5,6-tetrasubstituted pyrimidines 5a-d and 7a, e, f, g by condensation of thiouronium salts of type 3 with (ethoxymethylidene)malononitrile (4) and [bis(methylthio)methylidene]malononitrile (6), respectively, was first established in solution (Scheme 1) and successfully transferred onto solid support by using the polymer-bound thiouronium salt 11 (Scheme 3). Further investigations were directed toward a multidirectional cleavage procedure of the 2-(alkylsulfinyl) intermediates, obtained from the 2-(alkylthio)pyrimidines 7a (Scheme 2) or 12 and 14 (Schemes 3 and 4), with different nucleophiles to form highly substituted pyrimidines. In addition, fused-heterocycle derivatives 22a--h, 24a-c, and 26a-e were generated in good-to-excellent yields by condensation of 7a, e, h with versatile isocyanates and isothiocyanates, with subsequent alkylation (Scheme 5).