Parvineostemonine (1) was first isolated in the Chinese province Hanain by Prof. Dr. Ye and co-workers from Stemona parviflora in 2003. The first total synthesis of the Stemona alkaloid parvineostemonine was published in 2012 by Prof. Tu in a racemic fashion. Since the isolation no absolute configuration could be reported, and no detailed investigations into the biological profile have been published. Therefore, a synthetic access to both enantiomers of the natural product remained utmost important. The unique structure of parvineostemonine features a spiro-tetracyclic structure (rings A-D). The central piperidine ring C is fully substituted harbouring five stereogenic centers. Two rings A and B span across the piperidine ring in a bridgehead fashion. Ring A is a seven-membered ring consisting of a four-carbon bridge, ring B is a five-membered ring. Ring D constitutes a butenolide, spiro-annelated to ring C. Our idea was to design a total synthesis of both enantiomers of parvineostemonine (1) in an enantiodivergent fashion. Starting from literature known building blocks 2 and 3 two regioisomers arise from a [5+2]-cycloaddition reaction, which can be separated in the course of the synthesis and be transformed into both antipodes of the natural product. Further key-steps are a ring-closing metathesis and the installation of the spiro-annelated butenolide moiety. The synthesis of both enantiomers of parvineostemonine was accomplished on large scale and in 11 steps altogether starting from commercially available stating materials.

Total synthesis of parvineostemonine by structure pattern recognition - a unified approach to Stemona and Sarpagine alkaloids

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.