MICROBIAL TRANSFORMATION OF L-696,474, A NOVEL CYTOCHALASIN AS AN INHIBITOR OF HIV-1 PROTEASE

The microbiological transformation of L-696,474 [1], a novel cytochala sin that is an inhibitor of HIV- 1 protease, was investigated using Ac tinoplanes sp. ATCC 5377 1. Six hydroxylated metabolites 2-7 of 1 were isolated and purified using reversed-phase hplc. All six metabolites were found to have undergone hydroxylation at the C- 16 methyl group ( C-22) of 1. Three of the compounds, 3, 4, and 5, were further hydroxyl ated at the para (C-29), the meta (C-28), and both the para and the me ta, positions of the phenyl ring, respectively. Metabolites 6 and 7 we re shown to result from vicinal dihydroxylation on both C- 16 and its attached Me (C-22). The metabolite 7 was further hydroxylated on the m eta position of the phenyl ring. The structures of the metabolites wer e established using spectroscopic techniques including ms, H-1 nmr, C- 13 nmr, and various 2D nmr spectroscopy experiments.