Chemoenzymatic Synthesis of Pleiogenone A: An Antiproliferative Trihydroxyalkylcyclohexenone Isolated from Pleiogynium timorense

The first total synthesis of polyhydroxylated cyclohexenone 1 , isolated from Pleiogynium timorense and named pleiogenone A, is reported that also serves as a proof of structure and absolute configuration. Enzymatic dihydroxylation of benzoic acid with R. eutrophus B9 provided enantiomerically pure diene diol 6 . Elaboration of the carboxylate moiety to the alkyl side chain was followed by singlet oxygen cycloaddition to furnish an endoperoxide whose reduction with thiourea led to cyclitol 19 . Several protective operations were required before oxidation and the final extension of the side chain by a Wittig reaction. After final deprotection of the acetonide functionality the desired pleiogenone A ( 1 ) was obtained in 14 operations from benzoic acid.