SYNTHESIS OF 2',3'-CIS-FUSED PYRROLIDINO-BETA-D-NUCLEOSIDES AND THEIRCONFORMATIONAL-ANALYSIS BY 500 MHZ H-1-NMR

The unique ''off-template'' stereoselectivity in the intramolecular fr ee radical cyclization of 3-aza-5-hexenyl endocyclic radical has been demonstrated for the first time through the synthesis of 2',3'-cis-fus ed pyrrolidino-beta-D-nucleosides, 19a, 20a, 21a, 22a, 23a, 35a, 36a, 37a and 38a, which are not hithertofore available by any known procedu res. The 2'-linked chiral carbon (C(c)) in 19a, 20a, 21a and 22a has s hown 25:1 to 10:1 stereoselectivity depending upon the bulk of its sub stituent. The 3'-linked chiral carbon (C(c)) in 35a, 36a and 37a, on t he other hand, has shown only 4:1 to 2:1 stereoselectivity. Finally, a full conformational analysis of 2',3'-cis-fused pyrrolizdino-beta-D-n ucleosides 19a,20a, 21a, 22a,23a, 35a, 36a,37a and 38a is reported usi ng H-1-NMR at 500 MHz. The solution geometry of the furanose and the p yrrolidine rings were studied on the basis of vicinal proton-proton co upling constants using the concept of pseudorotation. The furanose rin gs in 19a - 23a have a geometry biased toward a South-type conformatio n 170 - 81 % S. 126-degrees < P(S) < 131-degrees (Cl'-exo-C2'-endo), 2 8-degrees < psi(m) < 32-degrees, rms error +/-0.051. In compounds 35a - 38a, the riboses have a conformation biased toward the North-type 1 approximately 90 % N, 20-degrees < P(N) < 38-degrees (C3'-endo) and 27 -degrees < psi(m) < 30-degrees, rms error +/-0.051. In compounds 19a - 22a, the pyrrolidine geometry is biased toward the North-type conform ation (C2'-exo), with a phase angle of pseudorotation Q(N) almost-equa l-to -28-degrees and a puckering amplitude psi m almost-equal-to 40'( rms error +/-0.5). In compounds 35a - 37a, the pyrrolidine has a geome try biased toward a South-type conformation (C2-endo), with Q(S) - 175 -degrees and psim - 39-degrees (rms error +/-0.8). The furanose and t he pyrrolidine rings share the C2'-C3' bond and have correlated confor mations. The pyrrolidine adopt a North-type conformation in 19a - 22a when the ribose is in a South-type conformation. In contrast. the pyrr olidine ring adopts a South-type conformation when the ribose is in a North-type conformation (in 35a - 37a)- Compounds 19a - 23a and 35a - 38a show a preference for the gamma+ conformation (approximately 70%). The glycosyl conformation for all pyrrolidine-fused systems was found to be anti.