反应详情

This was circumvented by the synthesis of the adenosine analog from its preformed heterocycle in the same manner as that used to obtain the guanosine analog. The known 2,7-diaminothiazolo[4,5-d]pyrimidine (27) served as the starting material (Scheme V). Treatment of 27 with nitrous acid under conditions similar to those used to prepare 13 provided 7-amino-2-chlorothiazolo[4,5-d]pyrimidine (28). The structure of compound 28 was verified by single-crystal X-ray analysis. Treatment of 28 with NaSH in DMF at 0° C. yielded the 2-mercapto derivative, 7-aminothiazolo[4,5-d]pyrimidine-2(3H)-thione (29). The conversion of the 2-thioxo function in 29 to a 2-oxo function was accomplished using cold alkaline hydrogen peroxide to yield 7-aminothiazolo[4,5-d]pyrimidin-2(3H)-one (30). Reaction of 30 with the benzoyl-protected sugar, 5, under the same glycosylation conditions (at room temperature) as used to produce the blocked guanosine analog, 6, resulted in the formation of the unexpected blocked 4-ribofuranosyl isomer, 7-amino-4-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2(3H)-one (31), as the only isomer detected and isolated. If, however, the same reaction was carried out at elevated temperature (80° C.), the predominant product obtained was the desired 3-ribofuranosyl isomer, 7-amino-3-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)thiazolo[4,5-d]pyrimidin-2-(3H)-one (32). Both isomers, 31 and 32. were deprotected using sodium methoxide in dry methanol to obtain 7-amino-4-β-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one (33) and 7-amino-3-β-D-ribofuranosylthiazolo[4,5-d]pyrimidin-2(3H)-one (34), respectively.

1. customresulted in the formation of the
2. customisolated
3. customIf, however, the same reaction
4. customwas carried out at elevated temperature (80° C.)
5. customthe predominant product obtained