Determination of absolute stereochemistry and an alternative synthesis of homopumiliotoxin 223G: identification on chiral GC columns with the natural alkaloid.

Abstract

An alternative asymmetric synthesis of (+)-(lS,9aS)-homopumiliotoxin 223G (1) was accomplished via (1R,2R, 9aS)-1-(benzyloxy)-2-hydroxy-1-methyl-3[(E)-isobutylidene]++ +quinolizidi ne (4), which was synthesized according to the intramolecular nickel(II)/chromium(II)-mediated cyclization of the N-(iodoalkenyl)aldehyde 2. Compound 4 was converted to the acetate and subjected to reduction with lithium in ammonia, whereupon deprotection of the O-benzyl group and removal of the acetoxyl group occurred in a single operation to afford (+)-homopumiliotoxin 223G. The same sequence using (+/-)-4 was applied to the synthesis of racemic 223G. Gas chromatography of a sample of racemic 223G showed no separation into enantiomers on four different cyclodextrin-based chiral GC columns. We found, however, that the O-acetates of (+/-)-223G gave a nearly baseline separation on either a beta-cyclodextrin column or a permethylated beta-cyclodextrin column. The O-acetate of synthetic (+)-223G was identical on either of these two columns, with the first eluting O-acetate from acetylated (+/-)-223G and also with the acetylated 223G present in a frog skin extract, thus allowing us to confirm unambiguously the 1S,9aS absolute configurations of natural 223G.

Cite this paper

@article{Kibayashi2000DeterminationOA, title={Determination of absolute stereochemistry and an alternative synthesis of homopumiliotoxin 223G: identification on chiral GC columns with the natural alkaloid.}, author={Chihiro Kibayashi and Shinobu Aoyagi and Ting Chung Wang and Katuva Saito and John William Daly and Thomas F. Spande}, journal={Journal of natural products}, year={2000}, volume={63 8}, pages={1157-9} }