文摘
Whole-cell biooxidation of bromobenzene with Pseudomonasputida 39D or the recombinantEscherichiacoli JM109 (pDTG601) yields(1S,2S)-3-bromocyclohexa-3,5-diene-1,2-diol(9a), which is protected as the acetonideand converted to vinylaziridines 7, 15a,63, and 64. Our route to(+)-pancratistatin features the coupling of a higherorder cyanocuprate (derived by ortho-metalation fromN,N-dimethyl-2-[(tert-butyldimethylsilyl)oxy]-3,4-(methylenedioxy)benzamide) with aziridine 7 to generate28, which contains the carbon framework of the titlealkaloid.Functional group manipulations resulted in the preparation ofepoxydiol 50, which was transformed in a uniquefashion and under mild conditions(H2O/PhCO2Na) to (+)-pancratistatin,thus completing a concise synthesis of(+)-pancratistatin in 14 steps from bromobenzene (2% overall yield).To improve this first generation attempt, anew route was devised utilizing carbomethoxyaziridine 64 andits coupling to the cuprate of 3,4-(methylenedioxy)bromobenzene. The adduct was converted to(+)-7-deoxypancratistatin in a total of 11 steps frombromobenzene(3% overall yield), and the basis for further improvement toward apractical synthesis of pancratistatin-type alkaloidswas formulated.