Migrastatin and Dorrigocins Are Shunt Metabolites of Iso-Migrastatin

Fermentation of Streptomyces platensis NRRL18993 typically accumulated migrastation (1), dorrigocin A (2) and B (3), and 13-epi-dorrigocin A (5). Supplement of XAD-16 resin to the fermentation, in contrast, resulted in exclusive production of iso-migrastatin (4). In vitro studies showed that 1, 2, 3...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2005-02, Vol.127 (6), p.1622-1623
Main Authors: Ju, Jianhua, Lim, Si-Kyu, Jiang, Hui, Shen, Ben
Format: Article
Language:English
Subjects:
Analysis
Antineoplastic agents
Biological and medical sciences
Chemotherapy
Chromatography, High Pressure Liquid
General pharmacology
Lactones - chemistry
Lactones - metabolism
Macrolides - chemistry
Macrolides - metabolism
Medical sciences
Pharmacology. Drug treatments
Piperidones - chemistry
Piperidones - metabolism
Spectrometry, Mass, Electrospray Ionization
Stereoisomerism
Streptomyces - metabolism
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Summary:Fermentation of Streptomyces platensis NRRL18993 typically accumulated migrastation (1), dorrigocin A (2) and B (3), and 13-epi-dorrigocin A (5). Supplement of XAD-16 resin to the fermentation, in contrast, resulted in exclusive production of iso-migrastatin (4). In vitro studies showed that 1, 2, 3, and 5 are stable in aqueous solution but 4 undergoes rapid conversion into 1, 2, 3, and 5 under the same condition. These results revealed that 4 is the only bona fide natural product biosynthesized by S. platensis, and 1, 2, 3, and 5 are shunt metabolites of 4. This study also established the stereochemistry of 2−5 with the exception of C-11 for 3 and 4. A mechanism for H2O-mediated regio- and stereospecific rearrangement of 4 to 1, 2, 3, and 5 is proposed and supported by incorporation of 18O from H2 18O.
ISSN:0002-7863
1520-5126
DOI:10.1021/ja043808i