289619-64-3Relevant academic research and scientific papers
Determination of absolute stereochemistry and an alternative synthesis of homopumiliotoxin 223G: Identification on chiral GC columns with the natural alkaloid
Kibayashi, Chihiro,Aoyagi, Sakae,Wang, Tzu-Chueh,Saito, Kosuke,Daly, John W.,Spande, Thomas F.
, p. 1157 - 1159 (2000)
An alternative asymmetric synthesis of (+)-(1S,9aS)-homopumiliotoxin 223G (1) was accomplished via (1R,2R,9aS)-1-(benzyloxy)-2-hydroxy-1-methyl-3[(E)-isobutylidene] quinolizidine (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 β-cyclodextrin column or a permethylated β-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.
