Total Synthesis of Gypsetin, Deoxybrevianamide E, Brevianamide E, and Tryprostatin B: Novel Constructions of 2,3-Disubstituted Indoles

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• 作者：Jeffrey M. Schkeryantz ; Jonathan C. G. Woo ; Phieng Siliphaivanh ; Kristopher M. Depew ; and Samuel J. Danishefsky
• 刊名：Journal of the American Chemical Society
• 出版年：1999
• 出版时间：December 29, 1999
• 年：1999
• 卷：121
• 期：51
• 页码：11964 - 11975
• 全文大小：401K
• 年卷期：v.121,no.51(December 29, 1999)
• ISSN：1520-5126

文摘

A concise and efficient total synthesis of the acyl-CoA:cholesterol acyltransferase inhibitor gypsetin(1) is described. The route features a straightforward method for the introduction of a reverse prenyl groupinto the C2-position of an N-phthaloyl-protected tryptophan (11). The total synthesis of gypsetin was completedby the dimethyldioxirane-promoted double-oxidative cyclization of a prefashioned diketopiperazine (19). Totalsyntheses of deoxybrevianamide E (24) and brevianamide E (25) following similar procedures are also described.The reaction of nucleophiles with in situ-generated 3-chloroindolenines provides a route to 2,3-disubstitutedindoles from 3-substituted precursors. Indications of the scope and limitations of such reactions are provided.A total synthesis of tryprostatin B (41), a diketopiperazine derived from an L-tryptophan derivative (bearinga prenyl group at the mages/gifchars/alpha.gif" BORDER=0> position of the indole) and L-proline, was accomplished. The key step involved theintroduction of the prenyl function onto a protected tryptophan congener (11). A route for the prenylation ofketones with virtually no competitive reverse prenylation is also provided.