Improved and reliable synthesis of 3'-azido-2',3'-dideoxyguanosine derivatives.
An improved synthesis of N2-protected-3'-azido-2',3'-dideoxyguanosine 20 and 23 is described. Deoxygenation of 2'-O-alkyl (and/or aryl) sulfonyl-5'-dimethoxytritylguanosine coupled with [1,2]-hydride shift rearrangement gave protected 9-(2-deoxythreo-pentofuranosyl)guanines (10, 12 and 16). This rearrangement was accomplished in high yield with a high degree of stereoselectivity using lithium triisobutylborohydride (L-Selectride). Compounds 10, 12 and 16 were transformed into 3'-O-mesylates (18 and 21), which can be used for 3'-substitution. The 3'-azido nucleosides were obtained by treatment of 18 and 21 with lithium azide. This procedure is reproducible with a good overall yield.
Timoshchuk
Victor A
VA
TriLink BioTechnologies Inc., San Diego, California 92121, USA.
Hogrefe
Richard I
RI
Vaghefi
Morteza M
MM
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; C051073:3'-azido-2',3'-dideoxyguanosine