9-Deazapurine nucleosides. The synthesis of certain N-5-β-d-ribofuranosylpyrrolo[3,2-d]pyrimidines

Several N-5 ribofuranosyl-2,4-disubstituted pyrrolo[3,2-d]pyrimidine (9-deazapurine) nucleosides were prepared by the single phase sodium salt glycosylation of 2,4-dichloro-5H-pyrrolo[3,2-d]pyrimidine ( 3 ) using 1-chloro-2,3-O-isopropylidene-5-O-(t-butyl)dirnethylsilyl-α-D-ribofuranose ( 2 ). Use of 2 for the glycosylation avoided the formation of “orthoamide” products 1 and provided an excellent yield of the β nucleoside, 2,4-dichloro-5-[2,3-O-isopropylidene-5-O-(t-butyl)dimethylsilyl-β-D-ribofuranosyl]-5H-pyrrolo[3,2-d]pyrimidine ( 4 ), along with a small amount of the corresponding α anomer, 5 . Compound 4 served as the versatile intermediate from which the N-7 ribofuranosyl analogs of the naturally-occurring purine nucleosides adenosine, inosine and guanosine were synthesized. Thus, controlled amination of 4 followed by sugar deprotection and dehalogenation yielded the adenosine analog, 4-amino-5-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidine ( 8 ) as the hydrochloride salt. Base hydrolysis of 4 followed by deprotection gave the 2-chloroinosine analog, 10 , and subsequent dehalogenation provided the inosine analog, 5-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]-pyrimidin-4(3H)-one ( 11 ). Amination of 10 furnished the guanosine analog, 2-amino-5-β-D-ribofuranosyl-5H-pyrrolo[3,2-d]pyrimidin-4(3H)-one ( 12 ). Finally, the α anomer in the guanosine series, 16 , was prepared from 5 by the same procedure as that used to prepare 12 . The structural assignments were made on the basis of ultraviolet and proton nmr spectroscopy. In particular, the isopropylidene intermediates 9 and 14 were used to assign the proper configuration as β and α, respectively, according to Imbach's rule.