Microbial Transformations of Natural Antitumor Agents. 16. Conversion of Leurosine to 10'-Hydroxyleurosine by Streptomyces Species

Rosazza, John P. N.

doi:10.1021/np50016a015

Cited by 6 publications

(2 citation statements)

References 13 publications

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“…Twenty microorganisms from our cult had previously demonstrated their cap molecular oxygen into the structures of, and alkaloid substrates (3, 5, 14,16,191 their potential to hydroxylate 171-est None of the cultures formed large qu products with estrone as the substrate. to be a better substrate for the pro( products by the same 20 microorgan cultures used in screening-scale experim larger amounts of mnore polar products w to be metabolites hydroxylated at othe eral, no genus specificity could be obser of catechol metabolites.…”

Section: Resultsmentioning

confidence: 99%

Microbiological hydroxylation of estradiol: formation of 2- and 4-hydroxyestradiol by Aspergillus alliaceus

Williamson¹,

Orden²,

Rosazza³

1985

Appl Environ Microbiol

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Microorganisms known to hydroxylate alkaloids, amino acids, and aromatic substrates were examined for their potential to hydroxylate 171-estradiol and estrone. Thin-layer chromatography of fermentation extracts revealed a wide range of steroid products. Aspergillus alliaceus (UT 315) was the only culture capable of producing good yields of catechol estrogens with 17f8-estradiol. The organism also transformed estrone but not to catechol products. Analytical experiments with high-performance liquid chromatography revealed that A. alliaceus formed 4and 2-hydroxyestradiol with yields of 45 and 16%, respectively. A preparative-scale incubation was conducted in 2 liters of medium containing 1 g of 170i-estradiol as substrate. 4-Hydroxyestradiol was isolated and identified by proton nuclear magnetic resonance and high-resolution mass spectrometry. Ascorbic acid was added to microbial reaction mixtures as an antioxidant to prevent the decomposition of unstable catechol estrogen metabolites. The microbial transformation of 17fi-estradiol by A. alliaceus provides an efficient one-step method for the preparation of catechol estrogens. Microbial transformations have long been valued for the production of nearly every class of steroid hormone product (4, 11, 18). Important reactions catalyzed by microbial enzymes include Al-dehydrogenation, side-chain cleavage

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Section: Resultsmentioning

confidence: 99%

Microbiological hydroxylation of estradiol: formation of 2- and 4-hydroxyestradiol by Aspergillus alliaceus

Williamson¹,

Orden²,

Rosazza³

1985

Appl Environ Microbiol

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“…Hydroxylated derivatives 6 and 7 (Fig. (2))were obtained in the course of metabolism studies of vinblastine 1 and leurosine 5 involving microbiological transformations [6,7]. Later, 12'-and 13'-hydroxyvinorelbine 8 (Fig.…”

Section: Substitutions At the A' Ringmentioning

confidence: 99%

Modifications in the upper or Velbenamine Part of the Vinca Alkaloids have Major Implications for Tubulin Interacting Activities

Fahy

2001

CPD

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Vinca alkaloids represent a chemical class of major interest in cancer chemotherapy. The lead compounds vinblastine and vincristine have been employed in clinical practice for more than thirty years and remain widely used to this day. Several hundred derivatives have been synthesised and evaluated for their pharmacological activities, the majority being modified in the vindoline moiety, bearing several reactive centers. These efforts led to the identification of the amido derivative vindesine, registered in Europe in 1980 and now available in several countries. Then novel chemistry permitted the semisynthesis of derivatives modified in the velbenamine "upper" part of the molecule, creating a new potential in the Vinca alkaloids medicinal chemistry: as a result, vinorelbine, obtained by C' ring contraction of anhydrovinblastine, and is now marketed worldwide. Several strategies aimed at the total synthesis of vinblastine derivatives have been investigated, giving the opportunity to design rationally certain compounds. Modifications in the D' ring appeared to induce dramatic changes in the tubulin interactions. These observations have been confirmed recently by the identification of unprecedented pharmacological properties exerted by the novel fluorinated Vinca alkaloid, vinflunine. This review will focus more specifically on derivatives which have been modified in the velbenamine part, with the aim of inducing different chemical and pharmacological properties.

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The Bisindole Alkaloids

Cordell

1983

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Microbial Transformations of Natural Antitumor Agents. 16. Conversion of Leurosine to 10'-Hydroxyleurosine by Streptomyces Species

Cited by 6 publications

References 13 publications

Microbiological hydroxylation of estradiol: formation of 2- and 4-hydroxyestradiol by Aspergillus alliaceus

Microbiological hydroxylation of estradiol: formation of 2- and 4-hydroxyestradiol by Aspergillus alliaceus

Modifications in the upper or Velbenamine Part of the Vinca Alkaloids have Major Implications for Tubulin Interacting Activities

The Bisindole Alkaloids

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