The synthesis of 3‐deazapyrimidine nucleosides related to uridine and cytidine and their derivatives

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Abstract
Condensation of 2,4‐bis(trimethylsilyloxy)pyridine (1) with 2,3,5‐tri‐O‐benzoyl‐D‐ribofuranosyl bromide (2) gave 4‐hydroxy‐1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)‐2‐pyridone (3). Deblocking of 3 gave 4‐hydroxy‐1‐β‐D‐ribofuranosyl‐2‐pyridone (3′‐deazauridine) (4). Treatment of 4 with acetone and acid gave 2′,3′‐O‐isopropylidene‐3‐deazauridine (6). Reaction of 4 with diphenylcarbonate gave 2‐hydroxy‐1‐β‐D‐arabinofuranosyl‐4‐pyridone‐O2←2′‐cyclonucleoside (7) which established the point of gylcosidation and configuration of 4. Base‐catalyzed hydrolysis of 7 gave 4‐hydroxy‐1‐β‐D‐arabinofuranosyl‐2‐pyridone (3‐deazauracil arabinoside) (12). Fusion of 1 with 3,5‐di‐O‐p‐toluyl‐2‐deoxy‐D‐erythro‐pentofuranosyl chloride (5) gave the blocked anomeric deoxynucleosides 8 and 10 which were saponified to give 4‐hydroxy‐1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐2‐pyridone (2′‐deoxy‐3‐deazauridine) (11) and its α anomer (9). Condensation of 4‐acetamido‐2‐methoxypridine (13) with 2 gave 4‐acetamido‐1‐(2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranosyl)‐2‐pyridone (14) which was treated with alcoholic ammonia to yield 4‐acetamido‐1‐β‐D‐ribofuranosyl‐2‐pyridone (15) or with methanolic sodium methoxide to yield 4‐amino‐1‐β‐D‐ribofuranosyl‐2‐pyridone (3‐deazacytidine) (16). Condensation of 13 and 2,3,5‐tri‐O‐benzyl‐D‐arabinofuranosyl chloride (17) gave the blocked nucleoside 22 which was treated with base and then hydrogenolyzed to give 4‐amino‐1‐β‐D‐arabinofuranosyl‐2‐pyridone (3‐deazacytosine arabinoside) (23). Fusion of 13 with 5 gave the blocked anomeric deoxynucleosides 18 and 20 which were deblocked with methanolic sodium methoxide to yield 4‐amino‐1‐(2‐deoxy‐β‐D‐erythro‐pentofuranosyl)‐2‐pyridone (2′‐deoxy‐3‐deazacytidine) (21) and its a anomer 19. The 2′‐deoxy‐erythro‐pentofuranosides of both 3‐deazauracil and 3‐deazacytosine failed to obey Hudson's isorotation rule but did follow the “quartet”‐“triplet” anomeric proton splitting pattern in the 1H nmr spectra.

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