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

Abstract

AbstractSeveral 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.