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 N4-acetyl-5′, 3′-di-O-acetyl-2′-O-methyl cytidine with N6-Bz-adenine provided N6-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 N2-isobutyryl (isopropylphenoxyacetyl) 2′-O-Me-guanosine through methylation of 5′,3′-O-TIPDSi derivative followed by selective N2-acylation, deamination and desylilation provided target compounds in 70% combined yield. (d) Mg2+ and Ag+ directed methylation of N1-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.