Acyclic-sugar nucleoside analogs. Thymine derivatives from acyclic d-galactose and d-glucose precursors

Abstract

Fusion of 2,3,4,5,6-penta- O-acetyl-1-bromo-1-deoxy-1- S-ethyl-1-thio- aldehydo- d-galactose aldehydrol ( 1) with bis(trimethylsilyl)thymine ( 2) gave a 1-epimeric pair of acyclic-sugar nucleoside derivatives ( 3a and 3b), which were saponified to their O-deacetylated analogs 4a and 4b. Similarly, the 1-methoxy ( 5) and 1-benzyloxy ( 8) analogs of the bromide 1 were converted into the corresponding protected nucleoside analogs 6 and 9, respectively; subsequent saponification gave the corresponding O-deacetylated derivatives 7 and 10. In the same way, 2,3,4,5,6-penta- O-acetyl-1-bromo-1-deoxy-1- S-ethyl-1-thio- aldehydo- d-glucose aldehydrol ( 11) was converted into the acyclic-sugar thymine nucleoside analog 13 by way of the pentaacetate 12. Exposure of 1-deoxy-1- S-ethyl-1-thio-1-(thymin-1-yl)- aldehydo- d-galactose aldehydrol ( 4) to conditions of acetolysis led to the pentaacetate 3, whereas similar treatment of the 1-(adenin-9-yl) analog ( 14) of 3 caused scission of the 1-substituents to give hepta- O-acetyl- aldehydo- d-galactose aldehydrol ( 15).