Microbial Transformations of Natural Antitumor Agents. 21. Conversions of Aphidicolin

Article abstract of DOI:10.1021/jo00138a016

Microbial transformations have been employed as a means of preparing analogues of the diterpene aphidicolin.Microbial transformation products were initially identified by thin-layer chromatography of fermentation extracts and then were prepared by larger scale incubations.Each microbial metabolite was subjected to structure elucidation employing carbon-13 and proton NMR, high-resolution mass spectrometry, and infrared analysis.Metabolites were identified as 3α-acetoxy-16,17,18-trihydroxyaphidicolane, 18-acetoxy-3α,16,17-trihydroxyaphidicolane,3α,16,17-trihydroxyaphidicolan-18-oate, 16,17,18-trihydroxyaphidicolan-3-one, 3β,16,17,18-tetrahydroxyaphidicolane, and 3α,6β,16,17,18-pentahydroxyaphidicolane.The availability of the microbial metabolites enabled the near complete elucidation of the carbon-13 NMR spectrum of aphidicolin.Biological evaluations of these compounds were made by using in vivo and in vitro techniques.None of the metabolites were active in an in vivo antitumor test system, while all of the compounds inhibited the uptake of the thymidine to P-388 leukemic cells in vitro.