Determination of absolute stereochemistry and an alternative synthesis of homopumiliotoxin 223G: identification on chiral GC columns with the natural alkaloid.
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.
Kibayashi
C
C
School of Pharmacy, Tokyo University of Pharmacy & Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan. kibayasi@ps.toyaku.ac.jp
Aoyagi
S
S
Wang
T C
TC
Saito
K
K
Daly
J W
JW
Spande
T F
TF
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001001:Anura; D002849:Chromatography, Gas; D002850:Chromatography, Gel; D003505:Cyclodextrins / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D007212:Indolizines; D009682:Magnetic Resonance Spectroscopy; D008387:Marine Toxins / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines; D013237:Stereoisomerism
D000470:Alkaloids; D003505:Cyclodextrins; D007212:Indolizines; D008387:Marine Toxins; D010880:Piperidines; C414694:homopumiliotoxin 223G