The synthesis of (+)-allopumiliotoxin 323B '

This paper describes the synthesis of (+)-allopumiliotoxin 323B ' (1) using the intramolecular [3+2]-cyclo-addition reaction of the (Z)-N-alkenyl-nitr one 4. This synthesis began with (R)-tert-butyl-3 -hydroxy-pent-4-enoate [( R)-13] which was obtained by enzymatic resolution with Amano PS lipase. A s eries of manipulations gave intermediate 17 and in situ coupling with 4-ben zoyloxybutanal lead to the (Z)-N-alkenylnitrone 4 which underwent an intram olecular [3 + 2]-cycloaddition re-action to give the isoxazolidine 3 as the major cycloadduct. Isoxazolidine 3 provided the piperidinone 24 which upon diastereofacial selective addition of MeMgBr gave the required tertiary al cohol 25. Formation of the indolizidine core 2 was achieved by an intramole cular S(N)2 reaction. The side chain was assembled from a Wittig reaction b etween the phosphorane 8 and the enantiomerically pure aldehyde 9. Further modifications afforded the aldehyde 7 which underwent an aldol condensation with the potassium enolate of the indolizidone core 2. Dehydration gave th e enone 37 which was converted into the anti-diol 38 by intramolecular hydr ide reduction. Finally, deprotection of the BOM protecting group gave (+)-a llopumiliotoxin 323B ' (1).