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Vindoline (la) was transformed to O-demethylvindoline (lb) by Sepedonium chrysospermum ATCC 13378 in 33% yield. Thin-layer and high-pressure liquid chromatographic methods distinguished lb from previously reported microbial metabolites of vindoline. The structural proof of lb was based on its mass spectral fragmentation pattern and on its chemical and nuclear magnetic resonance spectral properties.The Vinca alkaloids vincristine and vinblastine possess significant antitumor activity and are widely used clinically. They have resisted simple syntheses, and their structural complexity has hindered the preparation of other useful derivatives of the alkaloids by chemical methods. Microbial transformations are being examined for their potential to prepare potentially important Vinca alkaloid derivatives.Vindoline (la) is one of the monomeric Vinca alkaloids and one of the most abundant alkaloids in Vinca rosea L. Since it is more readily available than vincristine and vinblastine, it was used in an effort to identify new types of biotransformation products of this group of alkaloids. Previous reports document the production of a variety of metabolites of vindoline by streptomycetes. Known vindoline metabolites include ( Fig. 1): deacetylvindoline (Ic) and deacetyldihydrovindoline ether (2c) (9); dihydrovindoline ether (2a); 3-acetonyldihydrovindoline ether (2b); a ring contraction product known as 16-dehydroxy-14,15-epoxy-14-oxo-3-norvindoline (12); N-demethylvindoline (Id) (13); and a dimer consisting of two dihydrovindoline ether moieties linked through their 3 and 14 positions (11).This report describes selective cleavage of the methyl ether group of vindoline by Sependonium chrysospermum ATCC 13378. The reaction gives lb in 33% yields, and it is not complicated by the formation of other side products. MATERIALS AND METHODSMelting points were determined on a Thomas-Hoover apparatus and are uncorrected. Infrared spectra were determined on a Perkin-Elmer 267 grating infrared spectrophotometer. Nuclear magnetic resonance (NMR) spectra were determined on a VarianAssociates model T-60 spectrometer using tetramethylsilane as an internal standard. Low-resolution mass spectra were obtained on a Finnigan model 3200 spectrometer, and high-resolution mass spectral data were provided by the Department of Chemistry, Massachusetts Institute of Technology, Cambridge. UV spectra were obtained on a Beckman DK-2 instrument. Elemental analyses were determined by Integral Microanalytical Laboratories, Inc., Raleigh, N.C.Vindoline, deacetylvindoline, dihydrovindoline ether, N-demethylvindoline, 3-acetonyldihydrovindoline ether, and 16-dehydroxy-14,15-epoxy-14-oxo-3-norvindoline were obtained as authentic reference standards from Eli Lilly and Co., Indianapolis, Ind.The purity of each compound was verified by thinlayer chromatography (TLC), high-pressure liquid chromatography, and mass spectral analysis. Vindoline (7) dihydrovindoline ether and the dihydrovindoline ether dimer (11) were characterized by melting points and UV, NMR, and...

Microbial transformation studies were conducted with the antitumor alkaloid thalicarpine. Streptomyces punipalus (NRRL 3529) converted thalicarpine to (+)-hernandalinol, the structure of which was determined spectroscopically and by synthesis from the known alkaloid hernandaline. This unusual biotransformation reaction most likely occurs by oxidative cleavage of the isoquinoline ring from thalicarpine through the intermediate hernandaline, which then undergoes further reduction to hernandalinol.

Inkubation von o Vindolin (I) mit einer Kultur von Streptomyces griseus (UI 1158) führt zu dem Dihydrovindolinether (II) und einer Verbindung, der anhand spektroskopischer Untersuchungen (13C‐, 1H‐NMR, MS) die Struktur des Dimeren (III) zugeordnet wird.

Die Umwandlung von Thalicarpin (I) in (+)‐Hernandalinol (II) auf biologischem Wege wird untersucht.