TETRAHEDRON Tetrahedron 54 (1998) 331 I-3320 Biotransformation of Shiromool Derivatives by Rhizopus nigricans Cultures: Chemical-Microbiological Synthesis of Michelenolide Analogues And& Garcia-Granados’, Maria C. Gutikrrez, Antonio Martinez, Francisco Rivas Departrunento de Quimica Q&mica Facultad de Ciencias, Universidad de Granada. JosC M. Arias Departamento de Mcrobiologia Facuhad de Ciencias. Universidad de Granada. 18071GRANADA. (Spain). Received 3 I December 1997; accepted 22 January 1998 Kq Wor& Biotransformation: Sesquiterpenolides:6p-Gennacranolides: Shiromool: Rhizopus nigricans Abstract: The biotransformation of two derivatives of shinxnool was carried out with Rhrzopus nrgricans cultures to obtain 1 I- and i2- hydroxylated mnetabolites.The 1 I-hydroxyl germacrane compound was transfonned to 1 I-R and 1I-S I2-hydro.xyl derivatives which were oxidked with TPAF’ lo give michelenolide analogues. In the biotransformation processes. 28- 3a- and 9p-hydroxyl derivatives were also obtained. as well as a 2p. I 1 dihydroxylakd metabolite. 0 1998 Elsevier Science Ltd. All rights reserved. INTRODUCTION As part of a series of studies on ways to obtain sesquiterpene lactones from a non-lactone sesquiterpene compound, we carried out the semisynthesis of germacrane lactones from derivatives of shiromool’, an anti- insect feeding compound. Sesquiterpene lactones are a wide and varied group of compounds with biological activity*-‘. 6p- sesquiterpenolides. which are scarce in nature and have rarely been studied, are of interest because of their role as possible intermediates in some biogenetic pathways3. In biogenetic terms sesquiterpene lactones are formed from an initial hydroxylation at C-12 which evolves to a carboxylic acid. Subsequent enzymatically- mediated hydroxylation at C-6 or C-8 (and lactonization) yield the respective sesquiterpenolidess~“ ’ In previous papers, we reported the synthesis of 6P-eudesmanolides by chemical-microbiological means” .‘*, with the help of the microorganisms zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA Ckvularia lunata and Rhizopus nigricans. Also, we have developed a method to epimerize 6cr-sesquiterpene lactones13, more abundant in nature, to the corresponding 6p- sesquiterpenolides. The use of a microbiological pathway to obtain ll- and 12-hydroxyl derivatives of shiromool acetate (1) allowed us to obtain some michelenolide’4 analogues. 0040-4020/98/!$19.00 Q 1998 Elsevier Science Ltd. All rights reserved. PII: S0040_4020(98)ooo74-X