Nucleic acid related compounds. 29. Thionyl chloride reactions with adenine nucleosides. Course of nucleophilic displacements and a preferential route to the 2′-chloro-arabino isomer

Abstract

A multistage sequence gave 5′-O-pivalyl-3′-O-methyladenosine (2e) which was treated with thionyl chloride in hot pyridine to give the corresponding 2'-chloro-arabino product 3a. Hydrogenolysis using tri-n-butyltin hydride and deblocking gave 2′-deoxy-3′-O-methyl-adenosine (3b). Analogous treatment of a mixture of 3′(2′),5′-di-O-acetyladenosines (5a,b) with SOCl2-pyridine gave the 3′-O-acetyl-2′-chloro-arabino (6a) and 2′-O-acetyl-3′-chloro-xylo (7a) derivatives in a ratio of ∼3:2, respectively. Hydrogenolysis and deprotection gave 2′-deoxyadenosine (6c) and 3′-deoxyadenosine (7c) (∼3:2) in ∼45% overall yield from adenosine (based on recovered starting materials). This represents the first example of preferential external nucleophilic displacement at C-2′ (vs. C-3′) in an equilibrating purine ribonucleoside system. Treatment of 9-β-D-xylofuranosyladenine (9) with SOCl2–HMPA gave the 5′-chloro-5′-deoxy product 10a rather than the previously suggested 2′-chloro-2′-deoxy derivative.