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The resolution of the 1-tert-butylimidazo[1,5-a] [1,4]benzodiazepines 12, 25, and 31 is described. These compounds do not contain a center of symmetry but exist as conformational isomers due to the presence of a chiral plane. The resolution was carried out by the following sequence of reactions: (1) reduction of the 5,6-imine bond in 12, 25, and 31 to give the dihydro derivatives 13, 27, and 33, respectively, which contain two elements of symmetry, (2) resolution of 13, 27, and 33 employing optically active acids, and (3) oxidation of the enantiomers of 13 (13a, 13b), 27 (27a, 27b), and 33 (33a, 33b) to retroduce the 5,6-imine bond to give the enantiomers of 12 (12a, 12b), 26 (25a, 26b), and 31 (31a, 31b), respectively. As a consequence of the oxidation, the center of asymmetry is lost while the conformational integrity is mantained. The absolute configurations of 12b, 25b, and 31a were determined by single crystal X-ray analysis. Based on the biological activity of enantiomeric pairs, the [R] configuration is required for recognition at the benzodiazepine receptor complex

Streptomyces sp. X-14889 (NRRL 15517) has been found to produce a number of novel polyether antibiotics and an orange pigment. One of the antibiotics, X-14889B (3) was identified as ferensimycin A, which in turn is an isomer of the well-studied polyether antibiotic, lysocellin (1). Of the three other antibiotics, X-14889C (4) is a lower homolog of ferensimycin A and antibiotics X-14889A (2) and D (5) which are respectively the descarboxy and anhydro-descarboxy forms of this same molecule. The latter compound, X-14889D is of interest as it contains an ether bridge across the terminal tetrahydrofuranyl ring in an analogous relationship to that reported earlier for antibiotics X-14873A (6) and G.

Diastereomeric cis- and trans-tetrahydro-4-aryl-3-[(dimethylamino)methyl]-2H-pyranols derived from 3-[(dimethylamino)methyl]tetrahydro-4H-pyran-4-one (5), have been prepared and their configurations were established on the basis of ir data. The biologically more potent trans isomer 3 was resolved into its optical antipodes and the absolute stereochemistry of one of the enantiomers 14, was determined by X-ray crystallography. Some of the compounds showed analgesic activity comparable to codeine.

Diastereomeric cis- and trans-tetrahydro-4-aryl-3-[(dimethylamino)methyl]-2H-pyranols derived from 3-[(dimethylamino)methyl]tetrahydro-4H-pyran-4-one (5), have been prepared and their configurations were established on the basis of ir data. The biologically more potent trans isomer 3 was resolved into its optical antipodes and the absolute stereochemistry of one of the enantiomers 14, was determined by X-ray crystallography. Some of the compounds showed analgesic activity comparable to codeine.

The synthesis and structural characterization of the tertiary phosphines mesityldiphenylphosphine [PPh2( mes )], dimesitylphenylphosphine [ PPh ( mes )2] and a new phase of trimesitylphosphine [P( mes )3] have been carried out. Crystals of PPh2( mes ) are monoclinic, space group P21/c, with a 10.252(10), b 9.847(11), c 17.444(7) Ǻ, β 99.78(6)°, Z 4; R 0.059 for 2102 'observed' reflections. Crystals of PPh ( mes )2 are also monoclinic, space group P 21/c, with a 8.964(9), b 22.99(1), c 10.228(4) Ǻ, β 107.98(5)°, Z 4; R 0.058 for 2350 'observed' reflections. The new phase of P( mes )3 is monoclinic, Cc, a 11.390(5), b 12.034(4), c 17.564(9) Ǻ, β 104.22(4)°, Z 4 (R 0.060 for 1046 'observed' reflections), in which the molecule is disordered. A full report is given for the phase previously studied (triclinic), Pī , a 8.191(3), b 16.447(5), c 18.667(6) Ǻ, α 104.82(3), β 97.74(3), γ 100.07(3)°, Z 4; R 0.065 for 4964 'observed' reflections. The P-C bond distances are similar for the whole series of compounds with an average value of 1.833(1)Ǻ. Introduction if the mesityl groups results in an increase of the C-P-C angles from c. 103 to c. 110° with a concomitant flattening of the PC3 pyramid.

1-(S)-Hydroxy-2-(S, S)-valylamido-cyclobutane-l-acetic acid was isolated from a fermentation broth of an unidentified Streptomyces species X-1092. The structure was determined by single crystal X-ray diffraction analysis of the p-bromophenylcarbamyl derivative. The substance inhibits the growth of gram-positive microorganisms in a chemically defined medium but growth inhibition is partially reversed by L-cysteine.

This report describes the isolation and chemical characterization of antibiotic X-14766A, the first halogen containing polyether antibiotic, from fermented cultures of Streptomyces malachitofuscus subsp. downeyi. The structure of this novel antibiotic was determined by X-ray analyses of the thallium and rubidium salts. In addition to the chlorine atom, which is attached to a salicylic acid chromophore, the molecule contains a tricyclic di-spiroketal ring system and an ethyl ester group.

The studies which led to the complete structure elucidation of the antibiotic aurodox, including the chiralities of all eleven asymmetric centers and the cis–trans isomerism of all seven exocyclic double bonds, are summarized. Aurodox was correlated stereochemically with mocimycin. Thus, aurodox can be described as N-[7-[5(R)-[7-[1,2-dihydro-4-hydroxy-1-methyl-2-oxo-3-pyridinyl]-6-methyl-7-oxo-1(E),3(E),5(E)-heptatrienyl]tetrahydro-3(S),4(R)-dihydroxyfuran-2(S)-yl]-6(S)-methoxy-5,7(R)-dimethyl-2(E),4(E)-heptadienyl]-α(S)-ethyl-5,5-dimethyltetrahydro-2(R),3(R),4(R)-trihydroxy-6(S)-[1(E),3(Z)-pentadienyl]-2H-pyran-2-acetamide. Mocimycin, probably identical with kirromycin, is the corresponding N-desmethyl homolog.

The 5-amino-3-arylamino-1,2,4-oxadiazoles 2 are conveniently prepared by oxidative cyclization of the arylamidinoureas 10. The process is also capable of producing a variety of the 5-substituted-amino analogs 32 when the appropriately substituted guanidine 31 is employed as the substrate. Two different types of rearrangement leading to triazol-3-ones accompany cyclization depending on the choice of starting material. The structures of the rearranged products were established by X-ray crystallographic analysis and the reaction mechanisms leading to these unexpected products are discussed.

A new antibiotic, 3-O-oleandrosyl-5-O-desosaminylerythronolide A oxime (3) was produced from erythronolide A oxime (1) by the oleandomycin-producing culture, Streptomyces antibioticus ATCC 11891. The structure of 3 was determined by degradative studies and confirmed by X-ray analysis. Compound 3 was found to be less active, but more stable to acid, than erythromycin A oxime.

Fermentation of deposited cultures of Streptomyces conglobatus, known to produce the polyether antibiotic, ionomycin has resulted in the isolation and characterization of a second metabolite, conglobatin (C28H38N2O6). X-Ray analysis revealed a dimeric macrolide dilactone structure for conglobatin, similar to the structures of the mold metabolites vermiculin and pyrenophorin, from which the absolute configuration of conglobatin has been inferred. The dimer consists of two molecules of 7-hydroxy-8-oxazoyl-2,4,6-trimethyl-2-octenoic acid joined by two ester linkages.

Distyrylsulfone 1 reagieren mit dem ambidenten Nucleophil Hydroxylamin ausschlieslich unter doppelter Addition des Stickstoffs zu 4-Hydroxy-1,4-thiazinan-Derivaten 3. Diese bilden in Losung temperaturabhangige Epimeren-Gleichgewichte. Sowohl beim Erwarmen als auch beim Auskristallisieren erfolgt Depopulation eines Epimers. Strukturen und Phanomene werden durch Rontgenstrukturanalyse und NMR-Spektroskopie geklart. Reactions of 1,4-Pentadien-3-ones, 22. - Synthesis and Structure of the Epimers of 3,5-Diaryl-4-hydroxy-1,4-thiazinane 1,1-Dioxides Distyrylsulfones 1 react with the ambident nucleophile hydroxylamine only by double addition of nitrogen to give 4-hydroxy-1,4-thiazinane derivatives 3. In solution 3 consists of a temperature-dependent equilibrium mixture of two epimers. When heated or when crystallized one of the epimers is depopulated. The above phenomena and structures are elucidated by an X-ray analysis and by NMR spectroscopy.

γ-Epoxy sulfones in which the epoxide function is terminal yield cyclopropylmethanol derivatives on reaction with methyllithium or lithium diisopropylamide. In contrast, treatment of these epoxides with two equivalents of CH3MgI gives only cis-3-phenylsulfonylcyclobutanols. The cis-relationship between the OH and sulfonyl groups was proven in one instance by an X-ray structure determination. Internal γ-epoxy sulfones yield cyclopropylmethanols with all bases studied. All δ-epoxy sulfones studied furnished cis-3-phenylsulfonylcyclopentanols upon reaction with the Grignard reagent. These same epoxides gave either cyclopentanols or noncyclic products upon reaction with LDA; no cyclobutane ring containing products were obtained contrary to the expectations based on Stork's results with the corresponding epoxy nitriles (ref. 2). The mechanism of the Grignard-mediated reaction involves epoxide opening by iodide ion, α-sulfonyl Grignard formation, and, finally, cyclization. When LDA or CH3Li is used the products are formed by an intramolecular SN2 opening of the epoxide by an α-lithio sulfone.

The structure of the reduced photocycloaddition product between (±)-piperitone and methylcyclobutene, (3b), an important synthetic intermediate, was determined by direct methods from Ni-filtered CuKα diffractometer data. The crystals of the photoadduct, (3b), are tetragonal, space groupI41/a, witha = 22.909(4),c = 10.957(3) A, andd calcd = 1.027 g cm−3 forZ = 16 (C15H26O,M = 222.37). The structure was refined toR = 0.079. Bond distances and angles are normal.

A series of novel 2- and 3-acylmorphinans (8-14) was synthesized in our search for a potent analgesic agent with low addiction potential. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, the levorotatory 3-acetyl-N-(cyclopropylmethyl)morphinan (12) was found to be an orally active analgesic, comparable in potency to morphine (1), yet only weakly able to substitute for morphine (1) in morphine-dependent rats.

The isolation of three new terpenoid 5-methylcoumarins in the form of diastereomeric mixtures from a north Indian collection of Ethulia conyzoides is reported. Stereochemistries were deduced by X-ray analysis of a pure acetate isomer obtained on acetylation of one of the diastereomeric mixtures.

Mecanismes des reactions des methyl-4 (ou phenyl-«4») triazole-1,2,4 ine-1 diones-3,5 avec des olefines. Les produits principaux sont ceux d'une reaction ene avec formation de diazetidines

A simple and high yielding synthesis of metalla-2-indane-1,3-diones (phthaloyl metal complexes) by the insertion of low-valent transition metal complexes (ClRh(PPh3)3, ClCo(PPh3)3, Fe(CO)5) into benzocyclobutenedione is reported. The structure of the rhodium complex was established by an X-ray analysis.

A study of the static stereochemistry of 1,1,2,2-tetraphenyldisilane ( 1 ) and 1,1,2,2-tetramesityldisilane ( 2 ) by empirical force field calculations, X-ray diffraction, and 1 H NMR reveals that the preference for the anti conformation, exhibited by the unclamped 1,1,2,2-tetraarylethanes, is sustained in the analogous disilanes, although in somewhat attenuated form. This anti preference stands in contrast to the gauche preference of 1,1,2,2-tetraalkyldisilanes. Examination of 3 J HH coupling constants for R 2 HSiSiHR 2 ; (R = phenyl, mesityl, 2,6-dimethyl-phenyl, t -butyl, cyclohexyl) suggests the existence of a Karplus relation for H-Si-Si-H systems.

6-Bromo-4-fluoro-1,3-dinitrobenzol ist ein wertvolles Reagens zur Herstellung kristalliner Derivate von Aminen, Phenolen und Alkoholen. Die resultierenden 5-Bromo-2,4-dinitrophenylverbindungen konnen zur Charakterisierung und Kristallstrukturanalyse durch Rontgendiffraktion dienen. Aus den Antibiotika X-5108 und Mocimycin haben wir kurzlich ein neuartiges Octadienal isoliert, das mit 6-Bromo-4-fluoro-l,3-dinitrobenzol reagiert und in das Dimethylacetal umgesetzt wurde. Das resultierende Derivat wurde auf kristallanalytischem Wege als 8-(5-Bromo-2,4-dinitroanilino)-3(S)-methoxy-2(R),4-dimethyl-4(trans),6(trans)-octadienal-dimethylacetal identifiziert.

(S)-Alanyl-3-[alpha-(S)-chloro-3-(S)-hydroxy-2-oxo-3-azetidinylmethyl]-(S)-alanine was isolated from a fermentation broth of an unidentified Streptomyces species 372 A. The structure was determined by single crystal X-ray diffraction analysis. The substance inhibits the growth of several strains of gram-positive and gram-negative bacteria in a chemically defined medium but growth inhibition is relieved by addition of L-glutamine to the medium.