SYNTHESIS OF 1-(3-AZIDO-2,3-DIDEOXY-4-C-HYDROXYMETHYL-ALPHA-L-THREO-PENTOFURANOSYL)THYMINE, 1-(2,3-DIDEOXY-4-C-HYDROXYMETHYL-ALPHA-L-GLYCERO-PENTOFURANOSYL)THYMINE AND 1-(2,3-DIDEOXY-4-C-HYDROXYMETHYL-ALPHA-L-GLYCERO-PENT-2-ENOFURANOSYL)THYMINE

1-(2-O-Acetyl-3,5-di-O-benzoyl-4-C-benzoyloxymethyl-alpha-L-arabinofuranosyl)thymine (II) was converted to 2,2'-anhydro derivative V by selective deacetylation, mesylation and treatment with 1,8-diazabicyclo[5.4.0]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-alpha-L-pent-2-enofuranosyl)thymine (IX). Catalytic hydrogenation of IX gave 1-(2,3-dideoxy-4-C-hydroxymethyl-alpha-L-glycero-pentofuranosyl)thymine (X). Dehalogenation of compound VI with tributyltin hydride and debenzoylation afforded 1-(2-deoxy-4-C-hydroxymethyl-alpha-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-alpha-L-threo-pentofuranosyl)thymine (XXII).