A. Hernandez et H. Rapoport, CONFORMATIONALLY CONSTRAINED ANALOGS OF ANATOXIN - CHIROSPECIFIC SYNTHESIS OF S-TRANS CARBONYL RING-FUSED ANALOGS, Journal of organic chemistry, 59(5), 1994, pp. 1058-1066
Anatoxin is the most potent agonist known for the nicotinic acetylchol
ine receptor (nAChR). Although it possesses a semirigid structure, it
can adopt four distinctly different conformations. Further conformatio
nally constrained analogues of anatoxin should help to refine and disc
riminate among the current models for activation of this receptor. Thi
s report describes three s-trans ring-fused analogues which have been
synthesized starting from D-glutamic acid and 3-hydroxyacetophenone. A
ll of them have in common a 3-oxo-13-azatricyclo[8.2.1.0(2,7)]tridecla
ne structure. They represent the first fully constrained analogues of
anatoxin and are designed to serve as probes of the bioactive conforma
tion of anatoxin at the acetylcholine nicotinic receptor site.