Diastereoselective Synthesis of Allosecurinine and Viroallosecurinine from Menisdaurilide

Abstract

A new and versatile synthetic route to Securinega alkaloids is reported. The first synthesis of allosecurinine has been accomplished in seven steps and 40% yield, starting from (+)-menisdaurilide, using a vinylogous Mannich reaction as the key transformation. Similarly, viroallosecurinine has been synthesized from (-)-menisdaurilide.

Securinega Alkaloids: Complex Structures, Potent Bioactivities, and Efficient Total Syntheses

“…A key intermediate of the synthesis is the butenolide 74 , which represents the C and D rings in the final natural product and is the tert ‐butyldiphenylsilyl (TBDPS)‐protected form of the natural product (+)‐aquilegiolide. The route to compound 74 was based on related synthetic studies reported in the literature . Initially the synthesis was designed to yield 73 , which had been isolated from F. virosa in 2012 by Wang, Zhang, Ye and co‐workers .…”

“…The same group reported another strategy involving a key vinylogous Mannich reaction in 2008 . Their synthesis commenced from the natural product (+)‐menisdaurilide [(+)‐ 63 ], the synthesis of which they had reported previously, and a possible biogenetic relevance of the key transformation was suggested.…”

“… Total synthesis of allosecurinine ( 2 ) starting from the natural product (+)‐menisdaurilide [(+)‐ 63 ] reported by Busqué and de March et al. in 2008 …”

“…The A‐ring pyrrolidine fragment was introduced by a vinylogous Mannich reaction, applying the one‐pot procedure developed by Busqué, de March and co‐workers (Scheme ) . The reaction afforded an excellent yield of 90 % and only two out of four possible diastereoisomers were formed and could be separated chromatographically giving compound 82 .…”

“…Due to the structural similarity between secu′amamine E ( 88 ) and bubbialidine ( 72 ), we planned to adopt the remaining steps from our total synthesis of the latter alkaloid. By using the methodology described by Busqué, de March and co‐workers, butenolide 74 was converted into silyloxyfuran 104 (Scheme ). Because the stereogenic center of the butenolide moiety is lost during this step, the starting material could be utilized as a diastereoisomeric mixture.…”