Comparative structural studies of [3.1.0]-fused 2',3'-modified .beta.-D-nucleosides by x-ray crystallography, NMR spectroscopy, and molecular mechanics calculations

A [3.1.0]-Fused 2',3'-Modified β-D-Pyrazolo[3,4-d]pyrimidine Nucleoside

“…The furanose ring of the six-carbon sugar moiety of each molecule is flattened compared with 2'-deoxynucleosides, presumably due to fusion of the epoxide ring with the C(2')---C(3') bond. This result is similar to that observed in many [3.1.0]-fused 2',3'-modified nucleosides where the furanose ring is derived from a five-carbon sugar (Koole et al, 1991).…”

“…Thus, the epoxy O atoms are exo oriented. The epoxide ring has virtually the same impact on the furanoid conformation as has been observed with other [3.1.0]-fused 2',3'-modified nucleosides (Koole et al, 1991). In the almost planar furanoid rings, the C(1')---C(2.…”

“…The most common conformation around the C(4')--C(5') bond in normal nucleosides derived from five-carbon sugars is gauche-gauche (Sundaralingam, 1965). In the title nucleoside (2), however, the gauche-trans conformation was observed for A, B and C, whereas in the closely related 2',3'-O-anhydroadenosine, the gauche-gauche conformation (Koole et al, 1991) was observed. This difference is presumably due to the presence of an extra hydroxymethyl group at the C(5') position.…”

“…Some 2',3'-modified nucleosides effectively inhibit the action of several DNA polymerases including virus reverse transcriptase (Kraevskii et al, 1988;Chiggeavadze et al, 1989). This, together with the X-ray crystallographic studies on several [3.1.0]-fused 2',3'-modified /3-D nucleosides of various natural bases (Koole et al, 1991), has prompted us to report the synthesis and Xray structure of the [3.1.0]-fused 2',3t-modified nucleoside of pyrazolo [3,4-d]pyrimidine, (2). To the best of our knowledge this is the first report describing the synthesis and X-ray study of a novel [3.1.0]-fused 2',3'-modified nucleoside comprising a six-carbon furanose sugar and a pyrazolo [3,4-d]pyrimidine ring system, which is isomeric with the biologically important purine system.…”

First total synthesis of (+)-neplanocin B

“…A cyclopropane or an epoxy ring can confer such rigidity to the sugar ring, in which the equilibrium N ⇔ S is not observed indicating that the solution conformation is practically the same to that found in the crystal. 9 Neplanocin C (1), 10 is a good prototype of a conformationally locked nucleoside analogue, which is built on an oxabicyclic[3.1.0]-hexane system that allows this compound to exhibit the typical Northern-type (N) conformation, specifically in the 2 E geometry. This conformation is very close to a pure 3 T 2 (P = 0º) geometry as determined by the P value of the pseudorotational cycle (P value = 338.03º and ν max = 21.89º) from the solved X ray structure.…”