Microbial Transformations of Natural Antitumor Agents, 25. Conversions of 3-Ketoaphidicolin

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Abstract
Microbial transformation [by Chaetomium funiculum] experiments were conducted using 3-ketoaphidicolin (2) as a starting material. Metabolites were isolated by solvent extraction and chromatography, and structures were elaborated by cmr [carbon magnetic resonance] and PMR spectroscopy, ms [mass spectrometry] and IR analyses. Several microorganisms provided metabolites in excellent yields, including 3-epi-aphidicolin (4). 6.beta.-Hydroxy-3-ketoaphidicolin (5) and 19-nor-16,17-dihydroxyaphidicolan-3-one (6). The last compound was formed via oxidation of the primary alcohol functional group at position 18 to the corresponding .beta.-keto acid derivative which spontaneously decarboxylated. This reaction was analogous to the metabolic demethylation of sterol intermediates. Each metabolite was tested for antitumor activity in the P-388 leukemic test system, and in the 6C631 colon tumor model system. None of the compounds were active in vitro, and all were less active than aphidicolin in the in vitro P-388 test system.

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