Toluene Dioxygenase-Mediated cis-Dihydroxylation of Aromatics in Enantioselective Synthesis. Asymmetric Total Syntheses of Pancratistatin and 7-Deoxypancratistatin, Promising Antitumor Agents

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• 作者：Tomas Hudlicky ; Xinrong Tian ; Kurt Kö ; nigsberger ; Rakesh Maurya ; Jacques Rouden ; and Boreas Fan
• 刊名：Journal of the American Chemical Society
• 出版年：1996
• 出版时间：November 6, 1996
• 年：1996
• 卷：118
• 期：44
• 页码：10752 - 10765
• 全文大小：814K
• 年卷期：v.118,no.44(November 6, 1996)
• ISSN：1520-5126

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.