Nucleic acid related compounds. 36. Synthesis of the 2′-O-methyl and 3′-O-methyl ethers of guanosine and 2-aminoadenosine and correlation of O′-methylnucleoside 13C nmr spectral shifts

Abstract

A modified trimethylsilylation of guanosine (1) followed by in situ replacement of the 6-trimethylsilyloxy group with ammonia at 150 °C gave 2,6-diamino-9-β-D-ribofuranosylpurine (2) in 92% yield. Treatment of 2 with diazomethane in the presence of tin(II) chloride dihydrate gave the 2′-O-methyl (3) and 3′-O-methyl (4) ethers of 2 in 98% combined yield. The ratios of 3/4 could be varied from 51:47 to 34:64 by changing the amount of catalyst used. Treatment of 3 and 4 with adenosine deaminase resulted in clean conversion of these 2-aminoadenosine ethers to 2′-O-methylguanosine (5) and 3′-O-methylguanosine (6), respectively, in optimized yields of 40% and 54% overall from 1. The 13C nmr data for six ribonucleosides and their isomeric methyl ether derivatives have been correlated to provide a convenient method of identification.