Improved synthetic approaches toward 2′-O-methyl-adenosine and guanosine and their N-acyl derivatives

We developed several improved approaches toward 2'-O-methyl adenosine and guanosine and their N-acyl derivatives. (a) Transglycosylation of N-4-acetyl-5', 3'-di-O-acetyl-2'-O-methyl cytidine with N-6-Bz-adenine provided N-6-benzoyl-5'3'-di-O-acetyl-2'-O-methyl adenosine in 50% yield. (b) Regioselective methylation of 2-amino-6-chloro purine riboside with MeI/NaH followed by hydrolysis provided 2'-O-Me-guanosine in high yield. The same 2'-O-Me-precursor was transformed into 2'-O-Me-adenosine in 58% yield. (c) Very efficient transformation of 2,6-diamino-purine riboside into N-2-isobutyryl (isopropylphenoxyacetyl) 2'-O-Me-guanosine through methylation of 5',3'-O-TIPDSi derivative followed by selective N-2-acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg2+ and Ag+ directed methylation of N-1-Bzl-guanosine proceeded in >80% yield with ratio of 2'-O-Me/3'-O-Me=9:1. The same methylation of adenosine with Ag+ and Sr2+ acetylacetonates provided 2'-O-Me-adenosine in 75-80% yield. (C) 2000 Elsevier Science Ltd. All rights reserved.