SYNTHESIS OF 1-(3-AZIDO-2,3-DIDEOXY-4-C-HYDROXYMETHYL-α-L-threo-PENTOFURANOSYL)THYMINE, 1-(2,3-DIDEOXY-4-C-HYDROXYMETHYL-α-L-glycero-PENTOFURANOSYL)THYMINE AND 1-(2,3-DIDEOXY-4-C-HYDROXYMETHYL-α-L-glycero-PENT-2-ENOFURANOSYL)THYMINE

Article abstract of DOI:10.1135/cccc19930409

1-(2-O-Acetyl-3,5-di-O-benzoyl-4-C-benzoyloxymethyl-α-L-arabinofuranosyl)thymine (II) was converted to 2,2'-anhydro derivative V by selective deacetylation, mesylation and treatment with 1,8-diaza-bicyclo<5.4>undec-7-ene.Cleavage of the 2,2'-anhydro ring in compound V with hydrogen chloride or bromide afforded the respective 2'-chloro and 2'-bromo derivatives VI and VII.Reaction of compound VII with Cu/Zn couple and subsequent debenzoylation led to 1-(2,3-dideoxy-4-C-hydroxymethyl-α-L-pent-2-enofuranosyl)thymine (IX).Catalytic hydrogenation of IX gave 1-(2,3-dideoxy-4-C-hydroxymethyl-α-L-glycero-pentofuranosyl)thymine (X).Dehalogenation of compound VI with tributyltin hydride and debenzoylation afforded 1-(2-deoxy-4-C-hydroxymethyl-α-L-erythro-pentofuranosyl)thymine (XII).Tritylation of compound XII, followed by mesylation, detritylation and nucleophilic substitution with azide furnished 1-(3-azido-2,3-dideoxy-4-C-hydroxymethyl-α-L-threo-pentofuranosyl)thymine (XXII).