Photoamidation of unsaturated carbohydrates. Synthesis of 1-(3-C-carbamoyl-3-deoxy-beta-D-glucopyranosyl)-thymine and -cytosine

Abstract

The acetone-initiated photochemical addition of formamide to 1,2,4,6-tetra-O-acetyl-3-deoxy-alpha-D-erythro-hex-2-enopyranose (1) afforded 1,2,4,6-tetra-O-acetyl-3-C-carbamoyl-3-deoxy-alpha-D-glucopyransoe (2), 1,2,4,6-tetra-O-acetyl-3-C-carbamoyl-3-deoxy-alpha-D-allopyranose (3), 1,2,4,6-tetra-O-acetyl-3-C-carbamoyl-3-deoxy-alpha-D-altropyranose (4), and 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1-hydroxy-1-methylethyl)-alpha-D-mannopyranose (5), in 46, 13, 1, and 7% yields, respectively. Condensation of 2,4,6-tri-O-acetyl-3-C-carbamoyl-3-deoxy-alpha-D-glucopyranosyl bromide (produced from 2 with hydrogen bromide) with 2,4-bis(trimethylsilyl)thymine afforded 1-(2,4,6-tri-O-acetyl-3-C-carbamoyl-3-deoxy-beta-D-glucopyranosyl)thymine (6) in 40% yield. Deacetylation of 6 with sodium methoxide in methanol yielded the pure unprotected nucleoside 7. Similar condensation of the bromide from 2 with 2,4-bis(trimethylsilyl)-N4-acetylcytosine afforded the protected cytosine nucleoside 8 in 55% yield, which was converted into 1-(3-C-carbamoyl-3-deoxy-beta-D-glucopyranosyl)cytosine (9).