Oxidative biotransformation of stemofoline alkaloids

Abstract

Biotransformations of stemofoline (1a), (2 0 S)-hydroxystemofoline (2a), (11Z)-1 0 ,2 0-didehydrostemofoline (3a) and stemocurtisine (4) were studied through fermentation with Cunninghamella elegans TISTR 3370. Three new stemofoline derivatives; 6 R-hydroxystemofoline (1b), (2 0 S, 6 R)-dihydroxystemofoline (2b) and (11Z,6R)-1 0 ,2 0-didehydro-6-hydroxystemofoline (3b), together with the known compound 1 0 ,2 0didehydrostemofoline-N-oxide (3c), were produced by C-hydroxylation and N-oxidation reactions. Stemocurtisine was not biotransformed under these conditions. The transformed product 1b was four times more potent (IC 50 ¼ 11.01 ± 1.49 mM) than its precursor 1a (IC 50 ¼ 45.1 ± 5.46 mM) as an inhibitor against acetylcholinesterase.