4'-SUBSTITUTED NUCLEOSIDES .4. SYNTHESIS OF SOME 4'-HYDROXYMETHYL NUCLEOSIDES

Two complementary routes have been developed for the synthesis of 4-(acetoxymethyl)-l, 2, 3, 5-tetra-0-acetyl-D-erythro-pentofuranose (9). The first of these involves a mixed aldol condensation between 1, 2-O-isopropylidenea-D-xylo-pentodialdofuranose and formaldehyde which gives, as its major product, 4-(hydroxymethyl)-l, 2-0-isopropylidene-J-L-fbreo-pentofuranose (5a). Inversion of configuration at Ca is achieved via an oxidation-reduction sequence, and subsequent acetolysis furnishes 9. A more efficient route to 9 involves a mixed aldol condensation between 3-0-benzyl-l, 2-0-isopropylidene-a-D-ribo-pentodialdofuranose (12a) and formaldehyde followed by debenzylation, acetylation, and acetolysis. The condensation of 9 with a number of purine and pyrimidine bases and their analogues led to the preparation of a variety of 4'-hydroxymethyl nucleosides that have been screened for potential biological activities. © 1979, American Chemical Society. All rights reserved.