SYNTHESES VIA VINYL SULFONES .58. A TRIPLY CONVERGENT TOTAL SYNTHESISOF A SYMCHIRAL PYRROLIDINE-FUSED PROSTACYCLIN ANALOG

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.