Oxidative biotransformation of stemofoline alkaloids

Biotransformations of stemofoline (1a), (2′S)-hydroxystemofoline (2a), (11Z)-1′,2′-didehydrostemofoline (3a) and stemocurtisine (4) were studied through fermentation with Cunninghamella elegans TISTR 3370. Three new stemofoline derivatives; (6 R)-hydroxystemofoline (1b), (2′S, 6 R)-dihydroxystemofoline (2b) and (11Z,6R)-1′,2′-didehydro-6-hydroxystemofoline (3b), together with the known compound 1′,2′-didehydrostemofoline-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 (IC50 = 11.01 ± 1.49 µM) than its precursor 1a (IC50 = 45.1 ± 5.46 µM) as an inhibitor against acetylcholinesterase.