Improved Synthetic Approaches Toward 2′- O-Methyl-Adenosine and Guanosine and Their N-Acyl Derivatives

Abstract

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) Mg 2+ 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 Sr 2+ acetylacetonates provided 2′- O-Me-adenosine in 75–80% yield.