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 ) and araG ( 17 ) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6-chloro- and 2-amino-6-chloropurine ( 1 and 2 , 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 ( 4 and 5 , respectively) along with a minor amount of the N-7 positional isomers ( 6 and 7 ). Treatment of 4 with hydrogen sulfide in methanol containing sodium methoxide gave 2′-deoxy-6-thioinosine ( 10 ) in 93% yield. Similarly, 5 was transformed into 2′-deoxy-6-thioguanosine (β-TGdR, 11 ) in 71 % yield. Reaction of the sodium salt of 2 with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 8 ) gave N-7 and N-9 glycosylated products 13 and 9 , respectively. Debenzylation of 9 with boron trichloride at ?78° gave the versatile intermediate 2-amino-6-chloro-9-β-D-arabinofuranosyl-purine ( 14 ) in 62% yield. Direct treatment of 14 with sodium hydrosulfide furnished ara-6-thioguanine ( 16 ). Alkaline hydrolysis of 14 readily gave 9-β-D-arabinofuranosylguanine (araG, 17 ), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate afforded araG 5′-monophosphate ( 18 ).