Library

Notes: The four peripheral ester moieties of the title compound 5 are regioselectively hydrolyzed under mild conditions in the presence of β -cyclodextrin (10), providing a new entry to tetraphenylporphyrin derivatives with differently substituted Ph groups in the meso-positions. UV, 1H-NMR and mass spectroscopy of the inclusion complex 9 of 2,6-O-dimethyl-β-cyclodextrin (12) and 5 indicate a stoichiometry of 2:1 for 10/5. Moreover, calculations confirm NOE experiments consistent with the fact that the cyclodextrins 10 and 12 approach the Ph groups of the porphyrin with the small opening of the cavity (primary face).

Notes: N-(4-Nitrophenyl)oxamic acid 1, N-(2-fluoro-4-nitrophenyl)oxamic acid 7, N-(4-nitrophenyl)-trifluoroacetamide 3, and N-(2-methoxy-4-nitrophenyl)trifluoroacetamide 9 are non-competitive inhibitors of Vibrio cholerae sialidase with Ki-values ranging from 2.66 to 5.18 · 10-4 M. These compounds, and the N-acetylneuraminic-acid analogues 11-13 do not inhibit the sialidase and trans-sialidase activities from Trypanosoma cruzi; nor does N-(4-nitrophenyl)oxamic acid (1) inhibit the corresponding enzyme activities from T. brucei.

Notes: Repetitive treatment of the biopolymer P(3-HB) (molecular weight 〉 105 Dalton, storage or s-P(3-HB)), with lithium hexamethyl disilazanid (LHMDS) at -70° in THF leads to a mixture of oligomers with increasingly sharp distribution around a 15-, 30-, and 45mer. Discrete fragments are also isolated when P(3-HB) is heated under reflux (89°) in neat Et3N. Linear oligo(3-HB) derivatives (3-7) containing up to 96 3-HB units are synthesized using an exponential segment-coupling strategy. These oligomers are used to calibrate size-exclusion chromatography columns for the analysis of oligo(3-HB) samples from the different sources. The linear oligo-(3-HB) derivatives also served as a model with respect to the physical properties of high molecular weight P(3-HB) and were investigated as such by transmission electron microscopy (TEM) and by small- and wide-angle X-ray scattering (SAXS and WAXS). The thicknesses of the lamellar crystallites (long periods) formed by the 8mer, 16mer, and 32mer, are ca. 26, 52, and 53 Å, respectively, indicating that the 32mer molecules are folded once, very tightly, into a ‘hair-pin’-type conformation. High-molecular-weight P(3-HB), which was crystallized in a similar way, also has a lamellar crystallite thickness of ca. 50-65 Å. Thus, the treatment of P(3-HB) with LHMDS at low temperature causes etching of the amorphous regions, an effect well known in polymer science for studying the regularity of chain folding. The ca. 50-Å packing within the tight folds of P(3-HB) is discussed in view of its possible function in ion transport through cell membranes.

Notes: The Boc-protected tripeptides Boc-Val-Gly-Leu-OH (1), Boc-Leu-Sar-Leu-OH (2), Boc-Leu-Gly-MeLeu-OH (3), and Boc-Val-BzlGly-Leu-OMe (64), tetrapeptide Boc-Leu-Gly-Pro-Leu-OH (9), and pentapeptides Boc-Val-Leu-Gly-Abu-Ile-OH (4), Boc-Val-Leu-Sar-MeAbu-Ile-OH (5), Boc-Val-Leu-Gly-MeAbu-Ile-OH (6), Boc-Val-Leu-BzlGly-BzlAbu-Ile-OH (7), and Boc-Val-Leu-Gly-BzlAbu-Ile-OH (8) are prepared by conventional methods (Schemes 4-7) or by direct benzylation of the corresponding precursors (Scheme 8). Polylithiations in THF give up to Li6 derivatives containing glycine, sarcosine or N-benzylglycine Li enolate moieties (A-H). The polylithiated systems with a dilithium azadienediolate unit (C, F-H) are best generated by treatment with t-BuLi. The yields of alkylation of the glycine or sarcosine residues are up to 90%, with diastereoselectivities from nil to 9:1. Normally, the newly formed stereogenic center has (R)-configuration (i.e. a D-amino-acid residue is incorporated in the peptide chain). Electrophiles which can be employed with the highly reactive azadienediolate moiety are: MeI, EtI, i-PrI, allyl and benzyl bromide, ethyl bromoacetate, CO2, and Me2S2 (Schemes 11-13). No epimerizations of the starting materials (racemization of the amino-acid residues) are observed under the strongly basic conditions. Selected conformations of the peptide precursors, generated by shock-freezing or by very slow cooling from room temperature to -75° before lithiation, give rise to different stereoselectivities (Scheme 11). The latter and the yields can also be influenced by tempering the lithiated species before (Scheme 9) or after addition of the electrophiles (Scheme 12). Besides the desired products, starting peptides are recovered in the chromatographic purification and isolation procedures (material balance 80-95%). The results described are yet another demonstration that peptides may be backbone-modified through Li enolates, and that whole series of analogous peptide derivatives with various side chains may thus be produced from a given precursor.

Notes: The H-bonds of the enantiomeric ribosides 4 and 5 and their glycosidation by the diazirine 1 are described. HO-C(2) and HO—C(4) of 4 and 5 form a ‘flip-flop’ H-bonding system, with HO—C(3) acting as a H-bond donor to O—C(2) or O—C(4). HO—C(2) and HO—C(4) of monomeric 4 and 5 are thus the most strongly acidic OH groups. Glycosidation of 4 and 5 by 1 depends on the solvent, the temperature, and the concentration. It yields up to 91% of a mixture of anomeric pairs of the 1,2-, 1,3-, and 1,4-linked disaccharides 8-13 and 20-25, respectively, which were characterized as their diacetates 14-19 and 26-31 (Scheme). Glycosidation in CH2Cl2 and in dioxane yielded mostly the 1,3-linked disaccharides 10/11 and 22/23 (α/β ca. 4:1), while glycosidation in THF leads mostly to the 1,2- and 1,4-linked regioisomers (β〉α). There are small, but significant differences in the glycosidation of 4 and 5. These, the regio-, and the stereoselectivities are rationalized as the consequences of the stereoelectronic control of both the H-transfer from HO—C(2) or HO—C(4) to the intermediate carbene and of the formation of the glycosidic C—O bond, and of the coordination of the intermediate oxycarbenium ion with THF.

Notes: Achiral spiroactivated cyclopropanes are isomerized to optically active (R)-(cycloalk-2-enyl)-Meldrum's acids ( = (R)-5-(cycloalk-2-enyl)-2,2-dimethyl-1,3-dioxane-4,6-diones) in high yield and ee's up to 86% by catalytic amounts of cob(I)alamin in polar protic solvents.

Notes: Kinetic and equilibrium studies show that typical xenicanes such as dictyolactone (1) and 4-hydroxydictyolactone (3) undergo slow conformation medium-ring flipping between the predominant trans-(1a or 3a; Me(20) trans to H-C(3)) and the minor cis-conformers (1b or 3b; Me(20) cis to H-C(3); see Scheme 1). The formation of the latter is inhibited in heterocyclic-ring-opened congeners such as 18-acetoxy-4-hydroxydictyo-19-al (7). Molecular-mechanics calculations suggest that typical-xenicane cis-conformers are disfavoured by mainly C(4)-C(5) torsional strain. This is confirmed by the observation of two sizably populated cis-and trans-conformers for the unnatural 4-oxoxenicanes 10-12. Unusually facile thermal (E)→(Z) isomerization of xenicanes 1,3,10-12, and 7 is also observed (→ 13-17 and 9, resp.; Scheme 3), reflecting great strain relief in the transition state. Conflicting results in the literature now fit into this scheme which provides a basis for unravelling recognition phenomena with these biologically active systems.

Notes: (-)-Carbovir ((-)-1) was synthesized via the cyclic carbonate 2 in four steps starting from enantiomerically enriched (-)-(S)-(cyclopent-2-enyl)methanol ((-)-3).

Notes: During the examination of extracts from Oncinotis tenuiloba STAPF a new polyamine, N4-benzoylsperimidine (8), was isolated. For unambiguous structure elucidation, it was transformed into the diacetyl derivative 13, and the three possible N-benzoyl-substituted isomers of spermidine 5, 8, and 11 together with their peracetylated derivatives 12-14, respectively, were synthesized and identified.

Notes: Reductive electrocrystallization at a constant current density (11.0-11.5 μA/cm2) of millimolar solutions of [M(bpy)3](PF6)2, where M = Fe, Ru, or Os, and bpy = 2,2′-bipyridine in acetonitrile containing 0.1M Bu4NPF6 results in the formation of dark crystals on the Pt cathode. The crystals grow as long, thin, and shiny needles having a hexagonal cross section of 0.1-0.5 mm in diameter. Combustion microanalyses results are consistent with the composition for [Fe(bpy)3], [Ru(bpy)3], and [Os(bpy)3]. In addition, the chromophores are conserved, as confirmed by recording both the electronic and the 1H-NMR spectra after reoxidation of the electrocrystals in humid air. The spectra are identical to those for authentic samples of [Fe(bpy)3]2+, [Ru(bpy)3]2+, and [Os(bpy)3]2+. A ratio of 2.0 ± 0.1 e-/molecule is observed upon completion of the controlled potential electrolysis of a solution of [M(bpy)3]2+, which results in the precipitation of a dark solid and the almost complete fading of the color of the original solution. Unexpectedly, the crystals do not exhibit an ESR signal. These data indicate the formation of novel materials, crystalline [Fe(bpy)3], [Ru(bpy)3], and [Os(bpy)3].

Notes: The preparation of an analogue 3a of the acetylcholinesterase inhibitor, huperzine A (1), is described in which the pyridinone moiety of the natural product is replaced with a thiazolone moiety. The synthesis started from cyclohexane-1,4-dione monoethylene ketal (7) by first annulating the thiazole ring using the Gewald protocol (→ 8; Scheme 1) and then constructing the bicyclo[3.3.1]nonane substructure using our previously described Michael addition/aldol condensation methodology (Scheme 3). The central problem was the protection of the thiazolone carbonyl group; only the 2-unsubstituted thiazole survived the reaction conditions of the first half of the synthesis. Refunctionalization was later effected by lithiation and subsequent chlorination with hexachloroethane (30→31). Compound 3a was ineffective in the acetylcholinesterase inhibition assay in concentrations up to 14 μM.

Notes: Juvenoids 16-30, 32, 36, 38-41, 44-46, and 49-56 containing carbamate, carbonate, and urea moieties in the molecule were synthesized and subjected to a biological screening (Schemes 2-7, Table 2). Carbamate juvenoids 1-4 were used as reference compounds for a detailed structure-activity study of their analogues. A clear relationship between the nature of the side chain functional group and the biological activity was found. Surprisingly, not only the juvenoids 1-4 but also 38-41, the compounds with a reversed carbamate N,O-substitution pattern, showed very promising biological activity. In contrast, the carbonate and urea derivatives displayed a remarkably low activity. The relationship between the size and substitution at atoms C(2) and C(3) of the saturated ring and the biological activity is very complex and is still not completely understood.

Notes: Homogeneous asymmetric hydrogenation of a wide range of methyl and tert-butyl (Z)-2-(acylamino)-3-(heteroaryl)acrylates (see 1a-f and 2a-d, f, g, resp.) catalyzed by diphosphinerhodium catalysts was studied for the synthesis of enantiomerically pure 3-furyl-, 3-thienyl-, and 3-pyrrolylalanines (see 3a-f, and 4a-d, g; Scheme 1). The precursors, the (Z)-α-amino-α,β-didehydro esters 1a-f and 2a-d, f, g were prepared in high yields using the phosphorylglycine-ester method (Scheme 1). Isomerically pure (Z)-α-amino-α,β-didehydro esters were required to obtain the highest enantiomeric excesses (ee's) in the asymmetric hydrogenation, and the tert-butyl-ester strategy was beneficial in terms of both getting pure (Z)-α-amino-α,β-didehydro esters and obtaining high ee's in the hydrogenation. Finally, in contrast to the methyl-ester series, deprotection of the tert-butyl esters 4a-d, g was easily performed using CF3CO2H without any racemization.

Notes: According to their spectroscopic behavior, four classes of nonafulvenes may be distinguished, but, so far, only three classes have been identified. Type-A nonafulvenes (including parent 1a) are typically olefinic molecules with strongly alternating bond lengths and a nonplanar nine-membered ring. Type-B nonafulvenes are characterized by four pairs of equivalent ring H-atoms and ring C-atoms. Spectra of both Type-A and Type-B nonafulvenes are not dependent on temperature and solvent polarity. However, spectra of Type-C nonafulvenes (including prototype 1d with R1 = R2 = NMe2) are strongly influenced by temperature and solvent polarity due to an equilibrium 1⇄1± between the nonpolar olefinic 1 and dipolar planarized 1±. So far, Type-D nonafulvenes occurring exclusively in the dipolar form 1± were unknown. Synthetic attempts towards nonafulvenes of Type D are described and problems encountered in nonafulvene syntheses are discussed. Several new cyclononatetraenes and four new nonafulvenes (or nonafulvalenes) 31, 1n, 3, and 5 have been synthesized. Spectroscopic evidence shows that 11,12-bis(diethylamino)nonatriafulvalene 5 is the first Type-D nonafulvene.

Notes: Synthesis of optically active sesquiterpenes with a eudesmane C-skeleton from the chiral starting material thujone involves transformation of a tricyclic intermediate (1R,2R,4S)-1,7-dimethyl-4-(1-methylethyl)tricyclo[4.4.0.02,4]dec-6-en-8-one (2) into the bicyclic compound β -cyperone (5). Hydroxylation of 2 at C(5) or C(11) permits subsequent opening of the cyclopropane ring and rearrangement to β -cyperone. In this publication, studies involving hydroxylation of 2 by fungal cultures are presented. The resultant products are useful intermediates in efficient synthesis of eudesmane sesquiterpenes. Of five fungi tested, Rhizopus oryzae ATCC 11145 proved most versatile. It hydroxylates at the exocyclic C(11) position in high yield (70%) and, to a lesser extent, at C(5) (5%). Enzymatic activity appears at the end of growth phase and at least 2.2 g of 2 per liter can be metabolized without significant loss of product yield. A second fungus, Cunninghamella echinulata ATCC 9244, proved most useful for hydroxylation of derivatives of 2 for the preparation of derivatives of β -cyperone, although product yields were low (2-20%), some derivatives were nonreactive, and hydroxylation at C(9) occurred. The relationship between precursor structure and enzyme affinity is discussed.

Notes: L-Aspartic acid by successive N-tosylation, anhydride formation, and reduction was converted into (3S)-3-(tosylamino)butano-4-lactone (4). Electrophilic methylation of 4, subsequent iodo-esterification and nucleophilic methylation, followed by saponification and deprotection, gave (2S, 3R)-3-amino-2-methylpentanoic acid (2) with an ee of 〉 99% in seven steps and in an overall yield of 34%.

Notes: Reaction of the 3-silylated β-lactams 1 with glycoxalates gives bis-lactam 3, but the same reaction in the presence of 1 equiv. of Me3SiCl leads to the formation of the disilylated adducts 5. The latter is desilylated by (Bu4N)F yielding the monocarboxylates 7 of 3-methylidene-β-lactams, which, with oxidizing agents, give the spiro compound 8. The structure of 8 is established by spectroscopic data and a crystal-structure analysis.

Notes: Based on the natural abundance of 13C, in vivo 13C-NMR was used for the first time to monitor the metabolism of sucrose and hydroquinone (1) in cell suspensions of the plant Rauwolfia serpentina (L.) BENTH. ex KURZ. Cells converted sucrose extracellularly into α-D- and β -D-glucose as well as into β -D-fructofuranose and β -D-fructopyranose, respectively. The sugar mixture was completely taken up by the cells after 4 days. Hydroquinone fed at that time resulted in optimum conversion into its β -D-glucoside arbutin (2) within 10 h. A further metabolite, the primeveroside (3) of hydroquinone, appeared as a trace compound after 10 h. The formation of this diglycoside can be increased by further addition of sucrose.

Notes: A series of distannyl derivatives, 1-9, were studied for their application as phosphate-selective carriers in polymer-based liquid membranes. A drastically different potentiometric behavior was observed depending on the distance between the tin(IV) coordinating centers and the ligands attached to them. Some of the compounds examined, i.e. (PhSnBr2)2CH2(1) and (Me3SiCH2SnCl2CH2)2 (3) showed very high potentiometric selectivity towards phosphate over other lipophilic anions such as perchlorate and thiocyanate. Results indicate that (1) the optimal number of CH2 groups between the Sn-centers are either one or three, (2) the electron-withdrawing power of the organic ligands attached to Sn-centers strongly influences the overall response towards phosphate, and (3) the steric effect of the organic substituents is important in the potentiometric selectivity observed.

Notes: The X-ray crystal and molecular structures of 1-methyl- 1H-perimidin-2(3H)-one (5b) and 1,3-dimethyl-1H-perimidin-2(3H)-one (6) were determined. The crystals are built of piles of dimers faced head-to-head in 5b and of alternating independent head-to-tail molecules in 6, both along the b axis. Semiempirical calculations at the AM 1 level revealed that the eclipsed conformation of the Me groups with respect to the C=O group, found in the crystals, is the most stable. The lack of planarity of the whole molecules is a consequence of the packing forces since it is not found in the calculations. A comparative NMR study was carried out in solution (1H and 13C) and in the solid state (CP/MAS 13C) for 1H-perimidin-2(3H)-one (2) and 1H-benzimidazol-2(3H)-one (3) with the conclusion that in both heterocycles the oxo tautomer is the most abundant. The structure in the gas phase was approached by mass spectrometry. In the case of 3, the oxo tautomer loses CO after ionization, while the oxo form of 2 tautomerizes to the hydroxy form which loses, H2O after a [1,3]-H shift. AM 1 calculations were carried out on the ground and ionized states of 2.

Notes: NMR, potentiometric, and UV/VIS measurements were run to study the protonation and the In3+ and Cu2+ stability constants of 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (do3a, L). The protonation of do3a follows the typical scheme with two high and several low log KH values. Between pH 11 and 13, the protonation mainly occurs at the N-atom, which is not substituted by an acetate side chain. The In3+ complex is not appreciably protonated even at low pH values (pH ⋐ 1.7), whereas [CuL] can add up to three protons in acidic solution to give the species [CuLH], [CuLH2], and [CuLH3], the stability of which was determined. The formation rates of the Y3+, Gd3+, Ga3+, and In3+ complexes with do3a were measured using a pH-stat technique, whereas that of Cu2+, being faster, was followed on a stopped-flow spectrophotometer. In all cases, the reaction scheme implies the rapid formation of partially protonated intermediates, which rearrange themselves to the final product in the rate-determining process. ([MLH])in, an intermediate, in which the metal ion probably is coordinated by two amino acetate groups, proved to be the reactive species for Y3+, Gd3+, and Ga3+. The formation of [Cu(do3a)] was interpreted by postulating that either ([CuLH])in or ([CuLH])in, and ([CuLH2])in are the reactive complexes. The rates of dissociation of the Y3+, Gd3+, and Cu2+ complexes with do3a were studied spectrophotometrically. For Y3+ and Gd3+, arsenazo III was used as a scavenger, whereas for Cu2+ the absorption associated with d-d* transition was followed. For [Y(do3a)] and [Gd(do3a)], the rate law follows the kinetic expression kobsd = k0 + k1[H+]. The dissociation of [Cu(do3a)] goes through the proton-independent dissociation of [CuLH3], which is the main species at low pH.

Notes: Reaction of Di(tert-butyl)- and Diphenyldiazomethane and 1,3-Thiazole-5(4H)-thiones: Isolation and Crystal Structure of the Primary CycloadductReactions of diazo compounds with C=S bonds proceed via the formation of thiocarbonyl ylides, which, under the reaction conditions, undergo either 1,3-dipolar cycloadditions or electrocyclic ring closer to thiiranes (Scheme 1). With the sterically hindered di(tert-butyl)diazomethane (2c), 1,3-thiazole-5(4H)-thiones 1 react to give spirocyclic 2,5-dihydro-1,3,4-thiadiazoles 3 (Scheme 2). These adducts are stable in solution at -20°, and they could be isolated in crystalline form. The structure of 3c was established by X-ray crystallography. In CDCl3 solution at room temperature, a cycloreversion occurs, and the adducts of type 3 are in an equilibrium with 1 and 2c. In contrast, the reaction of 1 with diphenyldiazomethane (2d) gave spirocyclic thiiranes 4 as the only product in high yield (Scheme 3). The crystal structure of 4b was also determined by X-ray analysis. The desulfurization of compounds 4 to 4,5-dihydro-5-(diphenylmethylidene)-1,3-thiazoles 5 was achieved by treating 4 with triphenylphosphine in boiling THF. The crystal structure of 5f is shown.

Notes: A new alternative method for the preparation of amino-acid and peptide aldehydes based on reduction of corresponding phenyl esters with lithium tri(tert-butoxy)aluminium hydride is described.

Notes: The interaction between the uranyl ion and perchlorate in anhydrous acetonitrile has been investigated by FT-IR and Raman spectroscopy. Vibrations assigned to uncoordinated (u), monodentate (m), and bidentate (b) perchlorate anions were identified in 0.075M solutions. Quantitative data indicate that perchlorate is distributed as follows: 37 ± 2% are uncoordinated, 36 ± 7% are monodentate, and 27 ± 7% are bidentate. This is in agreement with the conductivity of the solutions which is at the lower end of the range accepted for 1:1 electrolytes. The splittings v4-v1(m) and v8-v1(b) of 147 and 246 cm-1, respectively, point to a large inner-sphere interaction. An equilibrium occurs between two differently coordinated species. Various amounts of DMSO were added to 0.05M perchlorate solutions (R′ = [DMSO]t/[UO22+]t = 1-10). The v7 (SO) and v22 (CS) vibrations of DMSO were used to determine the average number of coordinated DMSO molecules per uranyl ion, which is close to 4. Some bidentate perchlorate ions are still present in these solutions, but all the MeCN molecules (2.6 on average) are expelled out of the inner coordination sphere. The data can again be interpreted in terms of an equilibrium between differently coordinated species. The average coordination number of the uranyl ion is 4.4, as the perchlorate salt in MeCN solution, and may be somewhat smaller in the presence of DMSO. The possible presence of dimeric species is also discussed.

Notes: Synthesis of the Pyrrolizidine Alkaloid (±)-TrachelanthamidineThe important intermediate in the synthesis of the title compound 8 is the diastereoisomer mixture of ethyl 2-[2-(1,3 dioxolan-2-yl)ethyl]-5-oxopyrrolidine-3-carboxylate (3a/3b) which was prepared from nitromethane, acrylaldehyde, and diethyl fumarate (Scheme). Its reduction (NaBH4, t-BuOH, MeOH) gave exclusively the trans-alcohol 4a, which was converted to the protected pyrrolidine derivative 6. The deprotection and reduction of 6 gave the pyrrolizidine alkaloid 8, characterized as its hydrochloride.

Notes: We describe the synthesis of modified nucleoside triphosphates of the four DNA bases containing a 3′-amino group which were prepared from the corresponding 3′-azido derivatives. Introduction of the triphosphate and subsequent reduction of the N3 to the NH2 group led directly to the target molecules 6a-d. Furthermore, 3′-amino-2′,3′-dideoxynucleoside 5′-triphosphates proved to be potent inhibitors of the enzymatic synthesis of DNA catalyzed by the standard sequencing enzymes T7 DNA polymerase, sequenase version 2.0, Thermus aquaticus DNA polymerase, and Thermus thermophilus DNA polymerase. Both radioactive and fluorescent sequencing methods were applied successfully to the 3′-amino-modified terminators. Investigations in view of using these chain terminators according to Sanger's sequencing method for fluorescence labeling were done.

Notes: The synthesis of oligonucleotides containing 7-(2-deoxy-β -D-erythro-pentofuranosyl)adenine (N7Ad; 1) is described. Compound 1 was obtained from the precursor 4-amino-1H -imidazole-5-carbonitrile 2-deoxyribonucleoside 6 and was found to be much more labile than Ad. The N6-benzoyl protecting group (see 8) destabilized the N-glycosylic bond further and was difficult to remove by NH3-catalyzed hydrolysis. Therefore, a (dimethyl-amino)methylidene residue was introduced (→9). Amidine 9 was blocked at OH—C(5′) with the dimethoxytrityl residue ((MeO)2Tr), and phosphonate 4 as well as phosphoramidite 5 were prepared under standard conditions. Phosphonate 4 was employed in solid-phase oligonucleotide synthesis. Homooligonucleotides as well as self-complementary oligonucleotides were prepared. The oligomer d[(N7A)11-A] (11) formed a duplex with d(T12) (13). Antiparallel chain polarity and reverse Watson-Crick base pairing was deduced from duplex formation of the self-complementary d[(N7A)8-T8] (14).

Notes: The synthesis of aldehyde intermediates suitable for the preparation of indole alkaloids of the tacamine (1) type is described. The four possible aldehydes 4-7 were prepared from methyl 5-ethylnicotinate (8) in a few simple steps using a base-catalyzed epimerization as the final step (Schemes 1 and 2). The key aldehyde 4, which is an analogue of the important vincamine intermediate 3 (‘Oppolzer's aldehyde’), was finally converted into the indole alkaloid (±)-apotacamine (21).

Notes: A series of insect juvenile hormone analogs (juvenoids) was synthesized and studied. The basic skeleton of these juvenoids contains three rings and a short aliphatic subunit and bears two or three chiral centers (depending on the appropriate structure; see 6-9). The chiral center located in the 1,2-diphenoxypropane subunit has the configuration (RS), (R) (a series), or (S) (b series). The juvenoids were subjected to a biological screening, the preliminary results of which are briefly described.

Notes: The synthesis of the trisaccharide α-L-Fucp-(1 → 2)-β-D-Galp-(1 → 3)-β-D-GalpNAc-1-OPr (2) is described. The N-acetylgalactosamine 6 was obtained from 4 by an intramolecular displacement of a (trifluoromethyl)sulfonyloxy by a pivaloyloxy group with its concomitant migration from position 3 to position 4 (Scheme 1). The galactosyl donor 9 was obtained from 7 via 8 by regioselective opening of the orthoester function with AcOH/pyridine followed by treatment with CCl3CN and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (Scheme 2). Glycosylation of 6 with 9 in the presence of BF3 · OEt2 gave the disaccharide 10. Selective deprotection of 10 at O—C(2′) followed by glycosylation with 12 and by standard deprotection afforded the title trisaccharide 2 (Scheme 3). Preliminary biological testing showed that 2 is able to inhibit the binding of the monoclonal antibody MBrl to the target tumor cells MCF7 in a dose-dependent manner.

Notes: Four macrocyclic ligands have been synthesized: 1-oxa-4,7,10,13-tetraazacyclopentadecane (1), 1,4-dioxa-7,10,13-triazacyclopentadecane (2), 1,4-dioxa-7,11,14-triazacyclohexadecane (3), 1,4-dioxa-7,11,15-triazacycloheptadecane (4), one of them 3, for the first time. The protonation constants of the ligands and the stability constants of the complexes formed by the four ligands with some divalent first-series transition-metal ions, Cd2+ and Pb2+, were determined by potentiometric methods, in aqueous solution, at 25° and I = 0.10M (KNO3). The sequence of protonation of ligand 1 was studied by 1H-NMR spectroscopy. The Irving-Williams' order of stability is obeyed for the complexes of all the ligands, and the metal complexes of 1 present the higher values of stability. A drop in the stability of all the metal complexes studied is observed when the metal complexes of 1 are compared with the corresponding complexes of 2. The effect of the increase of the ring size of the macrocycle can be observed for metal complexes of the series of ligands 2 4, where, in spite of the slight increase of the overall basicity of the ligands (20.28, 22.25, and 24.96 for 2, 3, and 4 respectively), small differences in stability are found for the corresponding complexes of 2 and 3, but a significant drop occurs for all the metal complexes formed with the 17-membered ligand, specially for the larger metal ions like Mn2+ and Pb2+.

Notes: Assembly of Tetranuclear Ruthenium Complexes with Planar Metal Core by Condensation of Two Diruthenium Units Using Bridging Ligands: Synthesis and Molecular Structure of [Ru4(CO)8{μ2-P(Cy)2}4] and [Ru4(CO)8{μ4-P(Cy)}2{μ2}2](Cy = Cyclohexyl)The dinuclear complexes [Ru2(CO)6{μ-P(Cy)2}2] (1) or [Ru2(CO)4{μ-(HCO2)}2{P(Cy)2H}2] (2) react in THF solution at 160° to give the tetranuclear complexes [Ru4(CO)8{μ2-P(Cy)2}4] (3) and [Ru4(CO)8{μ4-P(Cy)}2{μ2-P(Cy)2}2] (4), as well as the trinuclear complex [Ru3(CO)7(μ2-H){μ2-P(Cy)2}3] (5). If the reaction is performed at 200°, the bicapped tetranuclear species 4 is obtained in a higher yield, whereas 3 and 5 are formed in trace amounts only. The phenyl derivatives [Ru2(CO)6{μ-P(Ph)2}2] (6) or [Ru2(CO)4{μ-(EtCO2)}2{P(Ph)2H}2] (7) react in a similar manner to give only the complex [Ru4(CO)8{μ4-P(Ph)}2{μ2-P(Ph)2}2] (8), analogous to 4. The molecular structure of 3 consists of a planar framework of four Ru-atoms, each Ru - Ru bond being bridged by a μ2-dicyclohexylphosphino ligand. The complex 4 represents a planar rectangular Ru core, both faces being capped by μ4-cyclohexylphosphinidene ligands and two opposite edges being bridged by μ2-dicyclohexylphosphino ligands.

Notes: By changing the O-alkyl substituents of the carbamate moiety of alkyl N-{2-{4-[(2-oxocyclohexyl)methyl]phenoxy}ethyl}carbamates and subsequent transformation of the oxo group in the cyclohexyl substituent, the juvenoids 1-20 were synthesized (Scheme). The methyl (1-4), propyl (9-12), isopropyl (13-16), and prop-2-ynylcarbamates (17-20) were subjected to biological screening on several non-related insect species (Tenebrio molitor, Galleria mellonella, Dysdercus cingulatus, and Pyrrhocoris apterus). Some of the juvenoids showed high biological activity and excellent selectivity with respect to target insect species (Table 2).

Notes: Two new phenylpentadienamides isolated from the culture filtrate of Streptomyces sp. were assigned the structures 5-(4-aminophenyl)penta-2,4-dienamide (2) and N2-[5-(4-aminophenyl)penta-2,4-dienoyl]-L-glutamine (3). In addition, 5-(4-aminophenyl)penta-2,4-dienoic acid (1) has been isolated, and its spectroscopic characteristics are reported for the first time. Compounds 1-3 exist in both the (2E,4E)- and (2E,4Z)-configurations. Electrospray and tandem MS, and HPLC/MS proved to be particularly suitable for the characterization of these metabolites.

Notes: The two-step alkylation of phenyl prop-2-enyl sulfone (1) with protected ω-bromoalkanols and 1-iodoalkanes (→3; see Scheme 1) followed by a Pd-catalyzed desulfonylation with LiBH4 affords a 96:4 mixture of vinylbranched, protected alcohols and corresponding ethylidene-branched isomers (see Scheme 2; 4 and 5, respectively). By utilizing the large difference in reactivity of mono- and trisubstituted C=C bonds towards singlet oxygen, the ethylidene derivatives are easily removed from the mixture by photo-oxygenation. The vinyl-branched compounds are inert to this reaction and can be conveniently isolated in highly pure form (99.5%) and ca. 45% overall yield.

Notes: The 2-(4-nitrophenyl)ethoxycarbonyl(npeoc) group, introduced 1984 as protecting group for exocyclic amino functions of nucleic-acid bases, reacts with amines under mild conditions to urea derivatives. Treatment of 2′,5′-di-O-acetyl-N6-[2-(4-nitrophenyl) ethoxycarbonyl]cordycepin (3) with NH3/MeOH overnight at room temperature affords cordycepin (4) and N6-carbamoylcordycepin (5). Preliminary investigations towards the elucidation of the reaction mechanism indicate that the aminolysis proceeds via an addition-elimination or an isocyanate mechanism, depending on the reaction conditions. The phenoxycarbonyl (phoc) group at N6 or N4 was chosen to study the mild conversion of carbamates with aromatic amines into ureas of adenosine and cytidine, respectively.

Notes: The reaction of Cu(AcO)2 · H2O and tridentate β-iminoketone ligands yielded four new copper complexes: acetato{4-{[2-(dimethylamino)ethyl]amino}pent-3-en-2-onato}copper(II) (1), triacetato{4-{[3-(dimethylamino)-propyl]amino}pent-3-en-2-onato}dicopper(II) (2), {4-{[2-(dimethylamino)ethyl]amino}-1,1,1-trifluoropent-3-en-2-onato}( trifluoroacetato)copper(II) (3), and pentaacetato{4-{[3-(dimethylamino)propyl]amino}-1,1,1-trifluoropent-3-en-2- onato}tricopper(II) (4). All compounds were coloured and air-stable solids. The crystal structures of 1 and the dioxane adduct of 3, μ-(1,4-dioxane)bis{{4-{[2-(dimethylamino)ethyl]amino}-1,1,1-trifluoropent-3- en-2-onato}(trifluoroacetato)copper(II)} (3a), were determined. Complex 1 consists of dimeric units [{Cu(AcO)L}2] in the solid state (L = β-iminoketonato ligand). In 3a, two [Cu(CF3COO)L] are linked via the O-atoms of the coordinated solvent 1,4-dioxane. Compound 1 crystallized in the monoclinic space group P21/n with a formula unit in a cell having the dimensions a = 11.152(6)Å, b = 10.104(3)Å, c = 11.805(7)Å, and β = 99.02(4)Å, and compound 3a crystallized in the triclinic space group P1 with a formula unit in a cell having the dimensions a = 8.709(3)Å, b = 9.439(4)Å, c = 12.395(3)Å, α = 67.57(3)°, β = 77.01(2)°, and β = 84.17(3)°. Mass spectra (MS), thermal analysis (DTA/TG), and evaporation-rate measurements are reported for all compounds. The influence of fluorination on the structure and volatility will be discussed.

Notes: Reaction of Ethyl Diazoacetate with 1,3-Thiazole-5(4H)-thionesReaction of ethyl diazoacetate (2a) and 1,3-thiazole-5(4H)-thiones 1a,b in Et2O at room temperature leads to a complex mixture of the products 5-9 (Scheme 2). Without solvent, 1a and 2a react to give 10a in addition to 5a-9a. In Et2O in the presence of aniline, reaction of 1a,b with 2a affords the ethyl 1,3,4-thiadiazole-2-carboxylate 10a and 10b, respectively, as major products. The structures of the unexpected products 6a, 7a, and 10a have been established by X-ray crystallography. Ethyl 4H-1,3-thiazine-carboxylate 8b was transformed into ethyl 7H-thieno[2,3-e][1,3]thiazine-carboxylate 11 (Scheme 3) by treatment with aqueous NaOH or during chromatography. The structure of the latter has also been established by X-ray crystallography. In the presence of thiols and alcohols, the reaction of 1a and 2a yields mainly adducts of type 12 (Scheme 4), compounds 5a,7a, and 9a being by-products (Table 1). Reaction mechanisms for the formation of the isolated products are delineated in Schemes 4-7: the primary cycloadduct 3 of the diazo compound and the C=S bond of 1 undergoes a base-catalyzed ring opening of the 1,3-thiazole-ring to give 10. In the absence of a base, elimination of N2 yields the thiocarbonyl ylide A′, which is trapped by nucleophiles to give 12. Trapping of A′, by H2O yields 1,3-thiazole-5(4H)-one 9 and ethyl mercaptoacetate, which is also a trapping agent for A′, yielding the diester 7. The formation of products 6 and 8 can be explained again via trapping of thiocarbonyl ylide A′, either by thiirane C (Scheme 6) or by 2a (Scheme 7). The latter adduct F yields 8 via a Demjanoff-Tiffeneau-type ring expansion of a 1,3-thiazole to give the 1,3-thiazine.

Notes: Oxindole 11, obtained on 3-[2′-(dimethylamino)ethyl]alkylation of oxindole 12, yielded, on stereoselective reduction with sodium dihydridobis(2-methoxyethoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10, obtained from 8 with MeI, gave, in nucleophilic displacements concurring with a Hofmann elimination, (±)-esermethole 6, (±)-5-O-methylphysovenol (14), (±)-5-O-methyl-1-thiaphysovenol (15), and (±)-1-benzyl-1-demethylesermethole (16). Syntheses of (±)-1-benzyl-1-demethylphenserine (18), (±)-1-demethylphenserine (19), and (±)-phenserine (4) from 6 and 16 are described. Optically active 8a and 8b, obtained by chemical resolution, similarly gave the enantiomers 6a and 14a-16a of the (3aS)-series (prepared earlier from physostigmine (1a)) and their (3R)-enantiomers. The anticholinesterase activity of (±)-4, (±)-18, and (±)-19 was compared with that of their optically active enantiomers.

Notes: Novel, more reliable and general reaction conditions for the α-alkylation of 4-monosubstituted 2-phenyloxazol-5(4H)-ones ( = 4-monosubstituted 2-phenyl-azlactones) rac-2 to 4,4-disubstituted 2-phenyloxazol-5(4H)-ones rac-1 were found (Scheme 2). Thus, a whole range of highly functionalized rac-1 were prepared in medium-to-good overall yields (40-90%, see Table). Azlactones rac-1 are ideal precursors for the synthesis of optically pure α,α -disubstituted (R)- and (S)-α-amino acids.

Notes: Insertion of the glycosylidene carbenes, derived from the gluco- and the manno-diazirines 1 and 2, into the Sn—H bond of R3SnH (R = Bu or Ph) leads to the fully substituted stannoglycosides 3-8 (53-77%). The 1,2-cis-configurated products are formed preferentially (α-D/β -D ranges from 2.5:1 to 5.1:1 with 1, and 1:1.3 to 1:4.2 with 2). Relative to CH2Cl2, THF favors formation of the equatorial Sn-glycosides. The stannylated (benzyloxy)glucals 9 and 10 were isolated as side products. The reaction of 1 with (Bu3Sn)2 yielded 9 (17% in CH2Cl2; 36% in CCl4) together with the azines 11 and the benzyloxyglucal 12. NMR Data of the Sn-glycosides 3-8 show evidence for an anomeric effect, 1J(C(1),H) being larger in the axial and 1J(Sn,C(1)) larger in the equatorial anomers.

Notes: The solution structures of the radical anion and the radical cation of the donor-acceptor molecules 3,4-di(1,3-dithiol-2-ylidene)-4-phenylbut-1-ene-1,1-dicarbonitrile (1) and 3,4-di(1,3-dithiol-2-ylidene)-4-phenylbut-1-ene-1,1,2-tricarbonitrile (2) are discussed based on cyclovoltammetric and ESR/ENDOR measurements. It is shown that the spin population of the radical anions is limited to the di- and tricyanoethene moiety and the coplanar 1,3-dithiole at C(3), whereas that of the radical cations resides mainly inside the two 1,3-dithiole rings. The energies of the long-wave bands in the electronic-absorption spectra of 1 and 2 correspond to the differences between the oxidation and reduction potentials and thus point to a charge-transfer character of these transitions.

Notes: Proton-hyperfine data are reported for the radical anions generated from azulene (1) and its alkyl derivatives 2-11 in 1,2-dimethoxyethane both ‘chemically’ with K and electrolytically. The alkyl derivatives are 1,3-dimethyl- (2), 5,7-dimethyl- (3), 1,3,5,7-tetramethyl- (4), 2-methyl- (5), 4,6,8-trimethyl- (6), 2,4,6,8-tetramethyl-(7), 1,3,4,6,8-pentamethyl- (8), 1,3,4,8-tetramethyl-6-propyl- (9), 6-(tert-butyl)-1,3,4,8-tetramethyl- (10), and 1,2,3,4,6,8-hexamethylazulene (11). Alkyl substituents at the odd-numbered centers μ = 1, 3, 5, and 7 partly shift the π-spin population from the seven- to the five-membered ring, whereas those at the even-numbered centers μ = 4, 6, and 8 exert an opposite effect on the π-spin distribution.

Notes: Cyclo[n]carbons (cyclo-Cn) are n-membered monocyclic rings of sp-hybridized C-atoms with unique electronic structures resulting from two perpendicular systems of conjugated π-orbitals, one in-plane and one out-of-plane. Several synthetic approaches to generate cyclo-C18 from stable precursors were investigated. In a six-step sequence from anthracene, tris(anthraceno)hexadehydro[18]annulene 5 was prepared and shown by laser-desorption time-of-flight mass spectrometry to generate C18 in three successive retro-Diels-Alder reactions, together with anthracene as the by-product. The attempted preparation of C18 by flash-vacuum pyrolysis of 5 using solvent-assisted sublimation only afforded anthracene next to polymers. The reaction of 1,6-bis(triisopropylsilyl)hexa-1,3,5-triyne with [Co2(CO)8] followed by exchange of two CO groups for a bridging bis(diphenylphosphino)methane (dppm) ligand gave Co complex 22 which, after removal of the silyl groups, was oxidatively cyclized to afford the very stable trimeric and tetrameric macrocycles 6 and 7, complexes with cyclo-C18 and cyclo-C24, respectively. An X-ray crystal structure established the identity of 6 and showed that the butadiyne units within the C18 core are considerably bent. Attempts to free cyclo-C18 from the coordinating metal atoms in 6 did not succeed, presumably due to the steric shielding of the Co-atoms by the dppm ligands. Low-temperature matrix isolation studies using IR and UV/VIS spectroscopy showed that irradiation of carbon oxide 2 (C24O6) leads to ketene intermediates and, by subsequent loss of six CO molecules, presumably to cyclo-C18.

Notes: The title compound is a condensation product of four guanidinium ions formed during crystallization of guanidinium nitrate. The crystal structure consists of infinite molecular ribbons stacked into layers which are rotated 58.5° with respect to each other and connected by two different networks of hydrogen bonds.

Notes: The title products are prepared via an efficient three-step synthesis which involves hydroalumination of methyl propiolate and Lewis-acid-promoted reaction with acetone in the presence of BF3 followed by two highly selective SN2′ reactions. The key step is the reaction of 2-(chloromethyl)acrylates with R2CuLi/ZnCl2 reagents which takes place with complete allylic rearrangement.

Notes: The Diels-Alder adduct of furan and 1-cyanovinyl (1′R)-camphanate was converted into methyl [(tert-butyl)-dimethylsilyl 5-deoxy-2, 3-O-isopropylidene-β-L-ribo-hexofuranosid] uronate ((+)-4). Reduction with diisobutyl-aluminium hydride gave the corresponding aldehyde which was condensed with the ylide derived from triphenyl-(propyl)phosphonium bromide to give (1R, 2S, 3S, 4S)-1-[(tert-butyl)dimethylsilyloxy]tetrahedro-2, 3-(isopropyl-idenedioxy)-4-[(Z)-pent-2′ -enyl]furan ((+)-7). Removal of the silyl protective group gave a mixture of the corresponding furanose that underwent Wittig reaction with the ylide derived from [8-(methoxycarbonyl)-octyl]triphenylphosphonium bromide to yield methyl (11R, 12S, 13S, 9Z, 15Z)-13-hydroxy-11, 12-(isopropylidene-dioxy)octadeca-9, 15-dienoate ((-)-9). Acidic hydrolysis, then saponification afforded (11R, 12S, 13S, 9Z, 15Z)-11, 12, 13-trihydroxyoctadeca-9, 15-dienoic acid (1).

Notes: Oligodeoxyribonucleotides containing 1-deaza-2′-deoxyadenosine ( = 7-amino-3-(2-deoxy-β-D-erythro-pentofuranosyl)-3H-imidazo[4, 5-b]pyridine; 1b) form Hoogsteen duplexes. Watson-Crick base pairs cannot be built up due to the absence of N(1). For these studies, oligonucleotide building blocks - the phosphonate 3a and the phosphoramidite 3b - were prepared from 1b via 4a and 5, as well as the Fractosil-linked 6b, and used in solid-phase synthesis. The applicability of various N-protecting groups (see 4a-c) was also studied. The Hoogsteen duplex d[(c1A)20] · d(T20) (11 · 13; Tm 15°) is less stable than d(A20) · d(T20) (12 · 13; Tm 60°). The block oligomers d([c1A)10-;T10] (14) and d[T10-(c1A)10] (15) containing purine and pyrimidine bases in the same strand are also able to form duplexes with each other. The chain polarity was found to be parallel.

Notes: Cyclo(-D-Leu-L-MeLeu-D-Leu-L-MeLeu-D-Leu-L-MeLeu-) (1) and cyclo(-L-Leu-D-Leu-L-MeLeu-D-Leu-L-Leu-D-Leu-) (2) were synthesized and used for a study of the interaction of β -rings in solution. In appropriate solvents, 1 and 2 formed dimers consisting of two β -rings connected through six interannular H-bonds and having the N -Me group(s) on the solvent-exposed face. The study also afforded indications that 2 formed different dimers of this kind, differing in the relative orientation of the two β -rings. These experimental observations provide strong support to the idea that unsubstituted D,L-alternating cyclooligopeptides, such as cyclo(hexaleucine), can self-assemble and give rise to long tubular stacks of β -rings.

Notes: Structures and Molecular Properties of Charge-Pertubed Molecules. 2, 3-Diphenylquinoxaline Radical Anions in Solution and in CrystalsThe Na⊕ and K⊕ radical-ion salts of 2, 3-diphenylquinoxaline seem to be (according to a structural database search) among the first ones of N-heterocyclic radical anions in crystals. The one-electron reduction in aprotic 1, 2-dimethoxyethan (DME) solution at metal mirrors and the crystallization under Ar have been preceded by cyclovoltammetric (CV) and ESR/ENDOR measurement. The first electron insertion at -1.63 V proves to be reversible, whereas the irreversible second step, which is accompanied by an overcrossing of the CV line, can be rationalized by an ‘ECE-DISP’ mechanism via a dianion redox disproportionation. The ENDOR spectrum resolves four 1H couplings and allows to simulate the ESR spectrum including the 14N hyperfine splittings. Both dark-blue single crystals of the radical ion salts \documentclass{article}\pagestyle{empty}\begin{document}$[2,3{\rm - diphenylquinoxaline}^{{.} \ominus} {\rm Met}^ \oplus ({\rm DME})]^.$\end{document} show unexpected similarities for Met⊕ = Na⊕, K⊕ despite the 36-pm difference in their ionic radii. The largest structural changes inflicted by the one-electron reduction of the N-heterocyclic molecule are observed in the vicinity of the N-centers bearing the highest effective nuclear charge. The DME-chelated metal cations coordinate at the N electron pairs and form Met⊕(DME)-bridged polymer chains of the radical anion, which are differently ondulated in the Na⊕ and K⊕ radical anion salts. The take-home lesson suggests that many more N-heterocyclic molecules might be analogously reduced under optimized conditions and isolated as single crystals.

Notes: The present work describes a new and efficient method for the preparation of either racemic or enantiomerically pure carbocyclic 2′-deoxyribonucleosides 1. Key steps are the efficient assembly of the racemic carbocyclic 2′-deoxyribose core (±)-12, its enzymatic resolution, and a new approach to covalently link the purine and pyrimidine bases with the cyclopentane moiety via the cyclic sulfate (+)-19. This total synthesis of enantiomerically pure and racemic carbocyclic 2′-deoxyribonucleosides 1 represents one of the most efficient approaches reported to date. Starting from cyclopentadiene, the four carbocycles corresponding to the naturally occurring 2′-deoxyribonucleosides could be prepared in 12 steps and 9-12% overall yield. For the corresponding racemic compounds, 10 steps were used with overall yields between 22 and 30%.

Notes: The oxidation reactions of a series of quinoxaline derivatives, using KMnO4 in the presence or absence of NaOH, are described. Neutral oxidation of 2-chloro- and 2, 3-dichloroquinoxalines 2-4 afforded the corresponding chloro- and dichloropyrazinedicarboxylic acids 13 and 14 in good yield. On the other hand, oxidation of quinoxalin-2(1H)-one and 1, 4-dihydroquinoxaline-2, 3-dione derivatives in alkaline medium gave different products, with the quinoxalin-2(1H)-one (5) forming 1, 4-dihydroquinoxaline-2, 3-dione (9), while various substituted quinoxalin-2, 3-dione derivatives (see 9-11) gave a new type of dimeric products. The structural assignments for the new compounds were based on spectroscopic data.

Notes: The excited electronic states of 2, 2-dimethylisoindene (1) have been studied by electron-energy-loss spectroscopy. Its vertical gas-phase triplet (13B2), and singlet (11B2) excitation energies are 1.61 and 3.19 eV, respectively. The excited states are thus lowered by 0.49 eV and 1.21 eV, respectively, when compared to the corresponding states of (all-E)-octatetraene, which serves as a reference compound. These shifts are partially reproduced by ZINDO calculations. The spectra give no evidence for a 21Ag state below the 11B2 state, but this lack of observation does not exclude its existence. The lowest triplet state T1(1) was further characterized by flash photolysis. T1(1) was observed as a transient intermediate, λ ≤ 350 nm, with a lifetime of 8 m̈s in degassed hexane. The adiabatic excitation energy of T1(1) was bracketed to the range of 1.1 ± 0.1 eV by energy-transfer experiments. Relationships between the energies of the lowest excited singlet and triplet states of 1 and the lowest excited doublet state of its radical cation \documentclass{article}\pagestyle{empty}\begin{document}${1}^{+\kern0pt {.}}$\end{document} - essentially a non-Koopmans' state - are discussed.

Notes: Synthesis of Phosphinico Analogues of PantetheineThe synthesis of phosphinico analogues 9a-c of pantetheine is described where the carbonyl group of one of the amide linkage is replaced by a methyl-, ethyl-, or phenylphosphinoyl group.

Notes: The gas-phase basic hydrolysis of clavulanic acid (a) was studied by using the AM1 semi-empirical method. The results obtained show that the hydroxyethylidene side chain at C(2) is pivotal to the stability of the different reaction products involved. The products with an open oxazolidine ring are more stable than those with a closed ring fused to the β-lactam ring. This behaviour differs from that of penicillins and cephalosporins where the most stable degradation products are those with an intact thiazolidine or dihydrothiazine ring, respectively, fused to the β-lactam ring. The different chemical reactivity of clavulanic acid relative to penicillins and cephalosporins could explain the disparate behaviour of the latter two types of compound towards β-lactamases. Once the acyl-enzyme intermediate of clavulanic acid has been formed, it can evolve with cleavage of the oxazolidine ring to form a difficult to deacylate compound.

Notes: The synthesis of 1- and 2-aryl-substituted (aryl = Ph, 4-NO2—C6H4, and 4-MeO—C6H4) 4, 6, 8-trimethylazulenes (4 and 3, respectively) in moderate yields by direct arylation of 4, 6, 8-trimethylazulene (8) with the corresponding arylhydrazines 13 in the presence of CuIIions in pyridine (see Scheme 4) as well as with 4-MeO—C6H4Pb(OAc)3 (16) in CF3COOH (see Scheme 5) is described. With 13, also small amounts of 1, 2- and 1, 3-diarylated azulenes (see 14 and 15, respectively, in Scheme 4) are formed. The 4-methoxyphenylation of 8 with 16 yielded also the 1, 1′-biazulene 17 in minor amounts (see Scheme 5). 4, 6, 8-Trimethyl-2-phenylazulene (3a) was also obtained as the sole product in moderate yields by the reaction of sodium phenylclopentadienide (1a) with 2, 4, 6-trimethylpyrylium tetrafluoroborate (2) in THF (Scheme 1). The attempted phenylation of 8 as well as of azulene (9) itself with N-nitroso-N-phenylacetamide (10) led only to the formation of the corresponding 1-(phenylazo)-substituted azulenes 12 and 11, respectively (Scheme 3).

Notes: In several steps, 5, 14-O-dimethylnaltrexone (3) and 5, 14-O-dimethylnaloxone (4) were prepared starting from 5, 14-O-dimethyloxycodone (5). Compound 3 exhibited opioid agonism in vitro (guinea-pig ileum and mouse vas deferens preparations) and antagonism in vivo (AcOH-writhing test in mice), while compound 4 was found to be an agonist in vitro and in vivo.

Notes: The synthesis of benzazepine analogues of the opium alkaloid noscapine (1) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester (4; readily available from 1) in several steps. X-Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo-form and thus has the same configuration as 1.

Notes: The synthesis of 3-glycosyloxylated flavylium ions (anthocyanins), in particular of callistephin (4), a natural anthocyanin, is described. The structural transformations in aqueous solution and molecular complexation with chlorogenic acid (7) and caffeine (8) of the synthesized pigments 3 and 4 are investigated and compared to those of the corresponding 3-methoxyflavylium ions 1 and 2 and to those of oenin (5) and malvin (6), two very common natural anthocyanins. The results are discussed in terms of the role played by the glycosyloxy residues in the chemical properties of anthocyanins. Anthocyanin molecular complexation (copigmentaion) is quantitatively investigated by UV/VIS spectroscopy and 1H-NMR. In particular, the UV/VIS spectroscopic data are interpreted using a general theoretical treatment, which, e.g., allows to demonstrate the formation of molecular complexes between the colourless forms of an anthocyanin and 8.

Notes: Single-Crystal Structures of a Donor-Acceptor-Substituted Cyclopentadiene, Its Cation and Its Anion Dimer: Different Distortion of a Five-Membered Carbon Ring1,4-Dimethyl-2,3,4,6-tetrahydro-1 H-cyclopentapyrazine-5,7-dicarbonitrile, its molecular cation, and its dimer dianion, generated by hydride abstraction or deprotonation, and crystallized, differ remarkably in their structures: the five-membered ring in the neutral compound is of (Z)-butadiene-type, whereas, in the tetrafluorborate salt, a peripheric NCCCCCN⊕ cyanine distortion occurs and in the sodium derivatives, solvated by either one or two 1,2-dimethoxyethane molecules, a cyclopentadienyl anion is formed. The structural perturbations induced by changing molecular charges are rationalized by extensive MNDO calculations, which on geometry optimization, reproduce the experimental structures and, in addition, provide charge distributions, further confirming the nN/π and π/π interactions already recognizable from the structural parameters.

Notes: The readily available title compounds 4a and 24 react with N-, O-, S-, and C-nucleophiles in presence of MnO2 to give the corresponding mono- or disubstituted 2H-azabenzimidazoles ( = azaisobenzimidazoles), e.g., 11-18 and 26a-h, respectively, or 2,3-dihydro-1H-azabenzimidazoles ( = dihydro-azabenzimidazoles) such as 9 and 10 and 27 and 28, respectively, by a 1, 4- or 1,6-Michael addition (Schemes 2 and 4). The bromo-dihydro-1H-azabenzimidazole 4b lost the Br-atom when treated with piperidine or morpholine yielding the corresponding disubstituted 2H-azabenzimidazole 21 (Scheme 3). Reductive ring opening of the substituted spiro compounds leads to mono- and disubstituted diaminopyridines which are intermediates for fused pyridine ring systems with substituents often not available by conventional routes and of potential pharmaceutical interest (see 32-37). E.g., starting from 4a, a three-step synthesis of the analgesic flupirtine maleate (= ethyl {2-amino-6-[(4-fluorobenzyl)amino]pyridin-3-yl}carbamate maleate = Katadolon®; 39) and of its non-fluorinated derivative D-7195 is described. Its analogue 40 was similarly made from the spiro compound 24.

Notes: The complexes of the type [ReH(CO)5-n(PMe3)n] (n = 4, 3) were reacted with aldehydes, CO2, and RC≡CCOOMe (R = H, Me) to establish a phosphine-substitutional effect on the reactivity of the Re-H bond. In the series 1-3, benzaldehyde showed conversion with only 3 to afford a (benzyloxy)carbonyltetrakis(trimethylphosphine)rhenium complex 4. Pyridine-2-carbaldehyde allowed reaction with all hydrides 1-3. With 1 and 2, the same dicarbonyl[(pyridin-2-yl)methoxy-O, N]bis(trimethylphosphine)rhenium 5b was formed with the intermediacy of a [(pyridin-2-yl)methoxy-O]-ligated species and extrusion of CO or PMe3, respectively. The analogous conversion of 3 afforded the carbonyl[(pyridin-2-yl)methoxy-O,N]tris(trimethylphosphine)rhenium (1) 7b. While 1 did not react with CO2, 2 and 3 yielded under relatively mild conditions the formato-ligated [Re(HCO2)(CO)(L)(PMe3)3] species (8 (L = CO) and 9 (L = PMe3)). Methyl propiolate and methyl butynoate were transformed, in the presence of 1, to [Re{C(CO2Me)=CHR}(CO)3(PMe3)2] systems (10a (R = H), and 10b(R = Me)), with prevailing α-metallation and trans-insertion stereochemistry. Similarly, HC≡CCO2Me afforded with 2 and 3, the α-metallation products [Re{C(CO2Me)=CH2}(CO)(L)(PMe3)3] 11 (L = CO) and 12(L = PMe3). The methyl butyonate insertion into 2 resulted in formation of a mixture of the (Z)- and (E)-isomers of [Re{C(CO2Me)=CHMe} (CO)2(PMe3)3] (13a,b). In the case of the conversion of 3 with MeC≡CCO2Me, a Re-H cis-addition product [Re{(E)-C(CO2Me)=CHMe}(CO)(PMe3)4] (14) was selectively obtained. Complex 11 was characterized by an X-ray crystal-structure analysis.

Notes: Chemistry of α-Amino Nitriles11. Mitteilung: [1]. . Exploratory Experiments on Thermal Reactions of α-Amino NitrilesThe paper extends a previously published report [4] on chemical properties of α-amino nitriles and of members of the C3H4N2 ensemble (Scheme 1) as observed in experiments carried out under non-aqueous conditions. The reactions investigated and the observations made are summarized in some detail in the English footnotes (*) referring to Schemes 1-17 and Fig. 1.

Notes: The conformational parameters responsible for sandalwood odor were investigated by the “active-analog approach”. The pharmacophoric (osmophoric) pattern of sandalwood-odor molecules can be outlined as three points: the OH group (point PI), a lipophilic group (point P2) 2.9-3.0 Å distant from the OH group, and a bulky rigid group (point P3), represented as a dummy atom in the middle of the alicyclic system (norbornane bicycle or cyclopentene ring) or a quaternary C-atom. This concept was tested on a series of representative sandalwood-odor compounds and on some structurally similar, but odorless substances.

Notes: The methylenation reaction of methyl azulene-2-carboxylates (cf. Schemes 1 and 2) with Tebbe's or Takai's reagent is described. When the prescribed amount of Takai's reagent is applied in a four-fold excess, the corresponding cyclopropyl methyl ethers are formed instead of the enol ethers (cf. Schemes 2 and 3). Similarly, methyl benzoate and methyl 2-naphthoate yield, after treatment with Takai's reagent and hydrolysis, the corresponding cyclopropanols 18 and 19, respectively (Scheme 3). The cyclopropyl methyl ether 4 or cyclopropanol 5 rearrange, on acid catalysis, into the l-(azulen-2-yl)propan-l-one 20 (Scheme 4). whose reduction with Et3SiH in CF3COOH yields the 2-propylazulene 21.

Notes: Chemistry of α-Aminonitriles. Formation of 2-Oxoethyl Phosphates (“Glycolaldehyde Phosphates”) from rac-Oxiranecarbonitrile and on (Formal) Constitutional Relationships between 2-Oxoethyl Phosphates and Oligo(hexo- and pentopyranosyl)nucleotide BackbonesOxiranecarbonitrile in basic acqueous solution at room temperature reacts regioselectively with inorganic phosphate to give the cyanohydrin of 2-oxoethyl phosphate (“glycolaldehyde phosphate”), a source of (the hydrate of) the free aldehyde, preferably in the presence of formaldehyde. In aqueous phosphate solution buffered to nearly neutral pH, oxiranecarbonitrile produces the phosphodiester of glycoladehyde as its bis-cyanohydrin in good yield. In contrast to mono- and dialkylation, trialkylation of phosphate with oxiranecarbonitrile is difficult, and the triester derivative is highly sensitive to hydrolysis. Glycolaldehyde phosphate per se is of prebiotic interest, since it had been shown [5] to aldomerize in basic aqueous solution regioselectively to rac-hexose 2, 4, 6-triphosphates and - in the presence of formaldehyde - mainly to rac-pentose 2, 4-diphosphates with, under appropriate conditions, rac-pentose 2, 4-diphosphates as the major reaction product. However, the question as to whether oxiranecarbonitrile itself has the potential of having been a prebiological natural constituent remains unanswered.Backbone structures of hexopyranosyl-oligonucleotides with phosphodiester linkages specifically between the positions 6′ → 4′, 6′ → 2′, or 4′ → 2′ of the sugar residues can formally be derived via the (hypothetical) aldomerization pathway, a combinatorial intermolecular aldomerization of glycoladehyde phosphate and bis(glycolaldehyde)-phosphodiester in a 1: 1 ratio. The constitutional relationships revealed by this synthetic analysis has played a decisive role as a selection criterion in the pursuit of our experimental studies toward a chemical etiology of the natural nucleic acids' structure. The Discussion in this paper delineates how the analysis contributed to the conception of the structure of p-RNA.The English Footnotes to Schemes 1-11 provide an extension of this summary.

Notes: Reactions of Fischer Carbene Complexes of 1,6-Methano[10]annuleneThe new Fischer carbene complexes 7, 8, and 10 of 1,6-methano[10]annulene as well as the bis(carbene) complex 15, were readily available in moderate yields by using the classical Fischer method (Schemes 1 and 2). The complexes 5 and 7 reacted easily with several alkynes under benzo-annulation conditions (Dötz reaction). Depending on the workup conditions, the new benzoquinones 16 and 17 (Scheme 5), hydroquinones 19 and 20 (Scheme 6), and protected hydroquinones 23-25 (Schemes 6 and 7) were synthesized. Surprisingly, in one run we were able to isolate the air-stable [Cr(η6-arene)(CO)3] complex 26 (Scheme 7). The X-ray structure and NMR data of 26 established a remarkable perturbation of the 10π perimeter of the 1,6-methano[10]annulene part in the hydroquinones 19-26, but no evidence of a σ-homoaromatic “bis(trinorcaradiene)” system. The first double Dötz reaction of 15 with hex-3-yne resulted in the formation of the “anti”-dibenzo-annulated 1,6-methano[10]annulene 32 (Scheme 8), which does not exist furthermore as a π-homoaromatic system, but as its σ-homoaromatic valence isomer.

Notes: First ever non-deformylating transdiazotization of acylacetaldehydes was achieved: the reactions of 2-azido-l-ethylpyridinium tetrafluoroborate (4) with acylacetaldehydes 3 proceeded partially without deformylation to yield 16 new α-diazo-β-oxoaldehydes 1 along with diazomethyl ketones 2, especially in the presence of NaOAc (Scheme 1, Tables 1 and 2). The product distribution was substituent-dependent and could be correlated quantitatively. This new diazotization reaction appears as an alternative, direct, and more general method for the synthesis of these diazooxoaldehydes. α-Oxocycloalkanecarbaldehydes 5 gave only traces (if any) of α-diazocycloalkanones 7, and rearrangement products 6 were isolated (Scheme 2). Mechanisms of the reactions are discussed (Schemes 4 and 5).

Notes: In the crystalline N,N′-dimethylated uracil derivatives 2a, b, the kinetically stabilized enol group forms an H-bond with O—C(4), as demonstrated by increased shielding of specifically labelled 2a and 2b in the 17O-NMR spectra (Δδ(17O)(C(4) - O) = -30 ppm); absence of dilution and solvent effects show that the H-bridge is intra-molecular, forming an eight-membered chelate ring. The (apparent) shielding effect Δδ(17O) in 2a, b is larger than that in salicylamide. The strong H-bond explains why the enols 2, in spite of the absence of steric hindrance, are kinetically stabilized.

Notes: The preparation of a macrocyclic diphosphine ligand 5 incorporating a binaphthyl unit and its NiII and PdII complexes, 6 and 7, is described. A complete assignment of 1H,- 13C-, and 31P-NMR data on the basis of 2D NMR spectroscopy (1H, 1H-, 13C, 1H-, 31P, 1H-, 31P, 13C-COSY) was possible for 5, and also - in part - for 6 and 7.

Notes: Oligoribonucleotides containing isoguanosine ( = 1,2-dihydro-2-oxoadenosine; isoG; 1) were prepared. The building block 2 was synthesized using the (dimethylamino)methylidene residue as NH2 protecting group. The monomethoxytrityl as well as dimethoxytrityl group were introduced at OH-C(5′) (→5 and 6). Silylation of 5 with triisopropylsilyl chloride formed the 2′-O-blocked derivative 7 almost exclusively. Reaction with PCl3/1,2,4-1H-triazole furnished the phosphonate 2 which was used in solid-phase synthesis of the oligoribonucleotides 10 and 11. RNAse T1 hydrolyzed U-A-G-U-U-isoG-U-U-A-G (10) at the 3′-site of G but not of isoG. The self-complementary oligomer (A-U-isoG-U)3 (11) formed a duplex which was less stable than that of (A-U)6.

Notes: Peptide mimetics of thyrotropin-releasing hormone (TRH) in which the peptide backbone is replaced by cyclohexane were synthesized from the cyclohexenone precursor 7. The aromatic side chains of the mimetics were derived from the corresponding aldehydes which were attached to the cyclohexenone via the Wittig reagent 8. The TRH mimetics are active in a mouse model of cognitive performance.

Notes: Stereoselective Syntheses of (Z)-(10-Methoxy-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-ylidene)acetic AcidTwo stereoselective syntheses for the antiinflammatory compound 1 ((Z)-isomer) are described. In the first approach (Strategy A, Scheme 1) the stereoselective synthesis of 1 was realized via the bicyclic compound 11 under thermodynamic conditions, followed by a thiophene annelation with retention of the double-bond geometry (Schemes 2-4). Optimized conditions were necessary to avoid (E/Z)-isomerization during annelation. In the second approach (Strategy B, Scheme 1), diastereoisomer 17b was obtained selectively from a mixture of the diastereoisomers 17b and 18b by combining thermodynamic epimerization and solubility differences (Scheme 5). Diastereoisomer 17b was converted into the tricyclic compound 23 using a novel thiophene annelation method which we described recently (Scheme 6). In a final step, a stereospecific ‘syn’-elimination transformed the sulfoxide 24 into the target compound 1 (Scheme 7). To avoid (E/Z)-isomerization, it was necessary to trap the sulfenic acid liberated during the reaction. The key reactions of both approaches are highly stereoselective (〉 97:3).

Notes: The 2-dansylethoxycarbonyl (Dnseoc) group was employed for protection of the 5′-hydroxy function in oligoribonucleotide synthesis by the phosphoramidite approach using the acid-labile tetrahydro-4-methoxy-2H-pyran-4-yl (Thmp) group for 2′-protection. The syntheses of monomeric building blocks, both phosphoramidites and nucleoside-functionalized supports, are described for the four common nucleosides adenosine, guanosine, cytidine, and uridine, and for the two modified minor nucleosides ribothymidine (= ribosylthymine) and pseudouridine.

Notes: A short regio- and stereoselective synthesis of two carbocyclic 3′-deoxynucleoside analogues is described, the key step of which consists in the photosensitized addition of MeOH to a cyclopent-2-enone derivative. As in both cases functional groups capable to react with each other are present in the same molecule, the synthetic compounds can form polymers similar to oligonucleotides.

Notes: The crystal structure of 3-phenyl-D3-trishomocuban-4-ol (4) was determined by X-ray crystallography (Fig. 1). Compound 4 was prepared from 8-phenylpentacyclo[5.4.0.02,6.03,10.05,9]undecan-8-ol in acidic medium. This is a facile method to prepare substituted trishomocubanes with a specific configuration at C(4).

Notes: The reaction of [Ir2Rh2(CO)12] with 1 mol-equiv. of PPh3 yields [Ir2Rh2(CO)11PPh3] (1) as a mixture of two isomers with the phosphine ligand axially bound either to one basal Rh-atom in the kinetically preferred isomer 1 R or to one basal Ir-atom in the thermodynamically preferred isomer 11. Both isomers are fluxional on the 13C-NMR time scale at low temperature due to CO scrambling. Around room temperature, a new type of fluxional process starts to operate which is responsible for the isomerisation 1R⇄11, i.e. the intramolecular migration of the reputedly inert PPh3 ligand from one metal centre to another. The activation volumes of conversions 1R → 11 and 11 → 1R are both positive, indicating that the migration of PPh3 is dissociative in character. This article reports the first application of variable pressure 31P-NMR to mechanistic studies.

Notes: The piperidine alkaloid (-)-allosedamine (1) has been synthesized, in 21% overall yield, in nine steps starting from the formyl-ester 4. The synthesis features the reaction cascade 7 → 3 → 2, involving asymmetric electrophilic enolate hydroxyamination, hydroxylamine/aldehyde condensation, and nitrone/styrene cycloaddition, as well as the reductive N/O cleavage-decyanation 12 → 1.

Notes: A new method for the preparation of N2-[(tert-butoxy)carbonyl]-L-amino-aldehydes from N2-[(tert-butoxy)carbonyl]-L-amino acids based on reduction of mixed anhydrides with LiAl(t-BuO)3H is described.

Notes: The cyclization reaction of aldehydes with Z- and Boc-protected β-hydroxyamino-acid esters (Tables 1 and 2), or of dipeptides containing serine or threonine at the N-terminus (Table 3), to give oxazolidine derivatives, occurs in the presence of isopropyl orthoformate and catalytic amounts of [Rh(MeCN)3(triphos)](CF3SO3)3. The reaction may be carried out under kinetic or under thermodynamic control, so that the ratio of the two possible epimeric products can be changed. The protecting group can be removed from the 3-position of the oxazolidine ring, and the resulting NH group can be coupled with another amino acid. Thus, a new method for the preparation of peptides containing β-hydroxy-amino acid-derived oxazolidines (‘pseudo-prolines’) is available. N-Neopentyl-substituted tripeptides are also described.

Notes: Contrary to earlier reports, the base-induced rearrangement of the 7-hydroxy-7H-indolenines derived from ajmalicine (1), yohimbine (5), corynanthine (6), methyl reserpate (16), and methyl isoreserpate (17) in each case furnished not just one, but two epimeric spiro-pseudoindoxyl derivatives which have opposite configuration at the spiro centre C(2). In all cases, the major component was shown by NOE experiments to be the A-type isomer (carbonyl group located below the plane defined by rings C and D). The thermodynamically less stable B-type pseudoindoxyl epimers 4, 10, 12, and 22 were isolated and characterized for the first time.

Notes: Synthesis of a Calicene Precursor for Retro-Diels-Alder ReactionsIn view of retro-Diels-Alder reactions (RDA reactions), the calicene precursor 9 has been synthesized in a comparably simple four-step synthesis by dibromocarbene addition at dibenzobarrelene (10 → 11, 44%), halogenlithium exchange followed by reaction with cyclopentenone (11→12, 91%) and H2O as well as HBr elimination (12→14→9, 43%) (Scheme 5). First experiments with respect to the thermal behavior of 9 show that, although RDA reaction seems to be relatively easily occurring according to the results of ‘Curie-Point’ pyrolysis, only anthracene and no calicene 2 has been detected so far.

Notes: The CuII-induced oxidative coupling of αω,-di(cyclopentadienyl)alkane-diides 6 (n = 2-5) has been shown to proceed mainly by an intermolecular pathway to give polymers 8, while the yield of intramolecular coupling 6 → 7 strongly decreases with increasing number n of C-atoms of the alkyl chain (Scheme 3). For n = 2, intramolecular coupling may be considerably enhanced by replacing the H-atoms of the CH2CH2 bridge of 6a (n = 2) by Me groups. In this case, intramolecular couplings 11 → 20 (Scheme 7) and 22 → 23 + 24 (Scheme 8) are accomplished with a total yield of 59% and 54%, respectively. All the intramolecular couplings investigated so far proceed stereoselectively to give the C2-symmetrical cyclohexanes 7a, 20 and 23 with a fixed chair conformation. These results are easily explained, if a conformational equilibrium E ⇄ F is operative in which large substituents R are assumed to enhance the gauche-conformation F which is the favored conformation for intramolecular couplings. Bridged dihydropentafulvalenes 20 and 23 are quantitatively rearranged to the thermodynamically favored bridged pentafulvenes 27 and 28 under base or acid catalysis, respectively (Scheme 9).

Notes: The new metal-free phthalocyanine 5 and phthalocyaninatometals 6-8 (M=Co, Ni, or Zn) fused in peripheral positions with four 13-membered tetrathiamacrocycles were prepared by cyclotetramerization of 2, 3, 6, 7, 9, 10-hexahydro-5H-[1, 4, 8, 11]benzotetrathiacyclotridecine-13, 14-dicarbonitrile in the presence of a suitable metal salt or a strong organic base. In contrast to the aza- or oxamacrocycle-fused analogs, the solubility of these phthalocyanines is very low. Complexation of the tetrathiamacrocycles of 7 and 8 with PdII or AgI to form pentanuclear products was accomplished from their suspensions.

Notes: Formation constants of ternary complexes of CuII with (S)-amino-acid amides (phenylalaninamide, prolinamide, and tryptophanamide) and (R)- or (S)-amino acids (valine, phenylalanine, proline, and tryptophan) were determined potentiometrically at 25° and I = 0.1M (KC1). Significant stereoselectivity was found for the systems (S)-tryptophanamide/proline, (S)-prolinamide/tryptophan, and (S)-phenylalaninamide/proline, the diastereoisomeric complexes with ‘homochiral’ (SS) being more stable than with ‘heterochiral’ (SR) ligands. The stereoselectivity observed may be explained on the basis of repulsive interactions between the ligand side-chain residues. The present data on the stability of mixed complexes in solution allow to draw some conclusions on the mechanism of chiral discrimination of amino acids in HPLC (reversed-phase) using CuII complexes of (S)-amino-acid amides as selectors for ligand-exchange chromatography (LEC).

Notes: Formation, X-Ray Crystal Structure, and Absolute Configuration of (-)-N-(Chloromethyl)galanthaminium ChlorideThe acetylcholinesterase inhibitor galanthamine (1), main alkaloid of several Narcissus species, readily forms a quaternary ammonium salt by reaction with the solvent CH2Cl2. The structure and absolute configuration of (-)-N-(chloromethyl)galanthaminium chloride (2) were determined by X-ray diffraction (R = 0.075 for 2775 observed independent reflexions) and NMR spectroscopy. The tetragonal crystals (space group P43) contain two crystallographically independent cations which do not differ significantly from one another. The CH2Cl group is attached to the quaternary N-atom in stereospecific (R)-configuration. In the crystal, the configurational position of the Me group at the N-atom of 2 differs from that of the crystalline free base 1. Hydrogen bonding is observed from the OH group at C(3) of 2 to the Cl- anion or to the Cl-atom of an adjacent cation.

Notes: Investigation of the metabolites from Gentiana rhodentha FR. (Gentianaceae) by LC-UV and LC-MS resulted in the isolation and identification of a new type of secoiridoid glycoside, rhodenthoside A (1), together with the known secoiridoids sweroside (2) and swertiamarin (3), as well as the known iridoids kingiside (4) and 8-epikingiside (5). The structures were established by 1D- and 2D-NMR, EI-MS, D/CI-MS, FAB-MS, CF-FAB, LC-MS, TSP, LC-MS, and LD-MS data in combination with chemical reactions.

Notes: Cyclopentadienyl C-glycosides (= glycosyl-cyclopentadienes) have been prepared as latent fulvenes. Their reaction with nucleophiles leads to cyclopentadienes substituted with (protected) alditol moieties and, hence, to enantiomerically pure metallocenes. Treatment of 1 with cyclopentadienyl anion gave the epimeric glycosyl-cyclopentadienes 6/7 (Scheme 1). Each epimer consisted of a ca. 1:1 mixture of the 1, 3-and 1, 4-cyclopentadienes a and b, respectively, which were separated by prep. HPLC. Slow regioisomerisation occurred at room temperature. Diels-Alder addition of N-phenylmaleimide to 6a/b ca. 3:7 at room temperature yielded three ‘endo’-adducts, i.e., a disubstituted alkene (8 or 9, 25%) and the trisubstituted alkenes 10 (45%) and 11 (13%). The structure of 10 was established by X-ray analysis. Reduction of 6/7 (after isolation or in situ) with LiAlH4 gave the cyclopentadienylmannitols 12a/b (80%) which were converted to the silyl ethers 13a/b (Scheme 2). Lithiation of 13a/b and reaction with FeCl2 or TiCl4 led to the symmetric ferrocene 14 (76%) and the titanocene 15 (34%), respectively. The mixed ferrocene 16 (63%) was prepared from 13a/b and pentamethylcyclopentadiene. Treatment of 6/7 with PhLi at -78° gave a 5:3 mixture of the 1-C-phenylated alcohols 17a/b and 18a/b (71%) which were silylated to 19a/b and 20a/b, respectively. Lithiation of 19/20 and reaction with FeCl2 afforded the symmetric ferrocenes 21 and 22 and the mixed ferrocene 23 (54:15:31, 79%) which were partially separated by MPLC. The configuration at C(1) of 17-22 was assigned on the basis of a conformational analysis. The reaction of the ribofuranose 24 with cyclopentadienylsodium led to the epimeric C-glycosides 27a/b and 28a (57%, ca. 1:1, Scheme 3). The in-situ reduction of 27/28 with LiAlH4 followed by isopropylidenation gave 25a/b (65%) which were transformed into the ferrocene 26 (79%) using the standard method. Phenylation of 27/28, desilylation, and isopropylidenation gave a 20:1 mixture of 33a/b and 34a/b (86%) which was separated by prep. HPLC. The same mixture was obtained upon phenylation of the fulvene 32 which was obtained in 36% yield from the reaction of the aldehydo-ribose 30 with cyclopentadienylsodium at -100°. Lithiation of 33/34 and reaction with FeCl2 gave the symmetric ferrocene 35 (88%). Similarly, the aldehydo-arabinose 36 was transformed via the fulvene 37 (32%) into a 18:1 mixture of 38a/b and 39a/b (78%) and, hence, into the ferrocene 40 (83%). Conformational analysis allowed to assign the configuration of 33-35, whereas an X-ray analysis of 40 established the (1S)-configuration of 38a/b and 40. The opposite configuration at C(1) of 38a/b and 33a/b was established by chemical degradation (Scheme 4). Hydrogenation (→41 and 44, resp.), deprotection (→ 42 and 45, resp.), NaIO4 oxidation, and NaBH4 reduction yielded (+)-(S)-43 and (-)-(R)-43, respectively.

Notes: Chiral triols 1-3 (‘tris(hydroxymethyl)methane’ derivatives), prepared from (R)-3-hydroxybutanoic acid and aldehydes, are used as center pieces of dendrimers. The triols may be employed as such or after attachment of spacers containing alkyl or aryl moieties (see 5 and 7). The branches combined with the original or elongated triols are those first reported by Fréchet (9-12, benzyl ethers of 3,5-dihydroxybenzyl alcohol and bromide). In this way, 1st-, 2nd-, and 3rd-generation chiral dendrimers without (13-15), or with aliphatic (16-18) or aromatic (19-21) spacers are prepared. The molecular weights range from 447 to 2716 Dalton. Two of the chiral triols, i.e., 2 and 3, are used as center pieces for chiral dendrimers containing 6 NH2, or 6 and 12 NO2 groups on the periphery (22-27), with 3,5-dinitrobenzoyl chloride as the branching unit. All compounds thus synthesized are of course monodisperse and are fully characterized. In some cases, the optical activity of the dendrimers indicates that conformationally chiral substructures might be present. The NH2- and NO2-substituted compounds avidly clathrate smaller molecules; they are sorbents exchanging host molecules through the gas phase.