Dc. Smith et Pl. Fuchs, SYNTHESES VIA VINYL SULFONES .58. A TRIPLY CONVERGENT TOTAL SYNTHESISOF A SYMCHIRAL PYRROLIDINE-FUSED PROSTACYCLIN ANALOG, Journal of organic chemistry, 60(9), 1995, pp. 2692-2703
The synthesis of symchiral 1-azatricyclo[6.3.0.0(2,6)]undeca-5-enyl pr
ostaglandin I-2 analog 34 is reported. Construction of the tricyclic s
keleton of 34 was accomplished in two steps by employing a triply conv
ergent approach which utilized vinyl sulfone technology. Introduction
of the heterocyclic subunit of 34 was achieved by an S(N)2'-thio-Clais
en rearrangement which efficiently coupled a thiolactam moiety to a su
itable allylic vinyl sulfone. Annulation of bicyclic vinyl sulfones 20
, 23, and 29 was accomplished via a conjugate addition of Lithium acet
ylide 11 to the vinyl sulfone moieties, followed by an intramolecular
S(N)2 displacement of a suitable nucleofuge. Competition between intra
molecular carbon alkylation and beta-elimination of stabilized nitroge
n anions from intermediate a-sulfonyl anions 20-i, 23-i, 29-i was disc
ussed. Refunctionalization of the resulting tricyclic skeleton was acc
omplished by employing standard literature protocols. Compound 34 was
found to be essentially inactive as an inhibitor of collagen-induced p
latelet aggregation, having an IC50 of > 10 mu M.