Total synthesis of (+)-pumiliotoxin 251D

Article abstract of DOI:10.1002/1099-0690(200210)2002:19<3315::AID-EJOC3315>3.0.CO;2-2

The convergent total synthesis of pumiliotoxins by attachment of the side chain to a suitably functionalized core indolizidinone derivative has been achieved. The use of an aldoltype addition condensation strategy, intended to provide for the stereoselective generation of the exocyclic double bond, gave no satisfactory results. The method of choice was a Homer olefination. Initially, the reactant core indolizidinone was converted into an α phosphono amide by amide enolate formation, enol phosphate generation, and a final phosphatephosphonate migration. The amido phosponates smoothly underwent Horner-type olefinations to allow successful introduction of the side chain with high Z selectivity in the exocyclic double bond. Similarly, the introduction of the phosphonate and the subsequent olefination could be run as a one-pot process. The final reductive removal of the lactam function provided (-)-8-epi-pumiliotoxin 209 F and (+)-pumiliotoxin 251 D. The structure of the pumiliotoxin 251 D was confirmed by X-ray analysis. Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.