Synthesis of ara-doridosine, a new arabinosyl nucleoside resistant to adenosine deaminase. X-Ray structure determination of 6-N,9(N)-diacetyl-1 (N)-methylisoguanine

Abstract

9-(β-D-Arabinofuranosyl)-1-(N)-methylisoguanine (2)(ara-doridosine) has been prepared via two stereochemically complementary synthetic routes, one of which utilized a recently described, novel nucleoside-base rearrangement reaction. The structural determination of several intermediates, some with unusual tautomeric forms stabilized by hydrogen bonding, was facilitated by use of ¹³C–¹H long-range coupling values. An X-ray diffraction analysis and a mass-spectral isotope fragmentation experiment also facilitated the structure elucidation of the key intermediates, 6-N,9(N)-diacetyl-1 (N)-methylisoguanine (6) and 6-N-methylisoguanine (7). respectively. The potential long acting antiviral agent (2) has been shown to be resistant to the enzyme adenosine deaminase.