Total synthesis of the Securinega alkaloid (-)-secuamamine A

Abstract

The first enantioselective total synthesis of the rearranged Securinega alkaloid (-)-secu'amamine A is reported starting from D-proline as the source of absolute chirality. The syntheis requires 15 steps starting from D-proline-derived N-trityl aldehyde 11 and proceeds in approximately 9% overall yield. Key steps include a stereoselective conjugate addition of pyrrolidino enedione 19 to afford indolizidine 24 as the major product and cyclization/lactonization of diketoester 25 to produce tetracycle 26. In addition, (1)H NMR NOE studies and X-ray analysis on the synthetic alkaloid have established that the indolizidine moiety is trans-fused.