A convenient synthesis of 2′‐deoxy‐6‐thioguanosine,ara‐guanine,ara‐6‐thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure

A simple and high‐yield synthesis of biologically significant 2′‐deoxy‐6‐thioguanosine (11),ara‐6‐thioguanine (16) andaraG (17) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6‐chloro‐ and 2‐amino‐6‐chloropurine (1and2, respectively) with 1‐chloro‐2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D‐erythro‐pentofuranose (3) gave the corresponding N‐9 substituted nucleosides as major products with the β‐anomeric configuration (4and5, respectively) along with a minor amount of the N‐7 positional isomers (6and7). Treatment of4with hydrogen sulfide in methanol containing sodium methoxide gave 2′‐deoxy‐6‐thioinosine (10) in 93% yield. Similarly,5was transformed into 2′‐deoxy‐6‐thioguanosine (β‐TGdR,11) in 71 % yield. Reaction of the sodium salt of2with 1‐chloro‐2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranose (8) gave N‐7 and N‐9 glycosylated products13and9, respectively. Debenzylation of9with boron trichloride at −78° gave the versatile intermediate 2‐amino‐6‐chloro‐9‐β‐D‐arabinofuranosyl‐purine (14) in 62% yield. Direct treatment of14with sodium hydrosulfide furnishedara‐6‐thioguanine (16). Alkaline hydrolysis of14readily gave 9‐β‐D‐arabinofuranosylguanine (araG,17), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate affordedaraG 5′‐monophosphate (18).