Synthetic routes to nucleoside analogs of N -substituted 1,3-thiazolidines

Abstract

Nucleoside analogs, namely 6-benzamido-9-(3-benzoyl-4(R))-methoxycarbonyl-2,2-dimethyl-thiazolidin-5(S)-yl)-9H-purine (7) and 6-chloro-9-[(3-benzoyl-2,2-dimethylthiazolidin-4(R)-yl)methyl]-9H-purine (8), were obtained from 3-benzoyl-5(S)-benzoyloxy-4(R)-methoxycarbonyl-2,2-dimethylthiazolidine (23) and 3-benzoyl-4(R)-hydroxymethyl-2,2-dimethylthiazolidine (24), respectively, the former, by treatment with 6-benzamidochloromercuripurine and titanium tetrachloride in 1,2-dichloroethane and the latter, by treatment with 6-chloropurine, triphenylphosphine, and diethyl azodicarboxylate in tetrahydrofuran. Compound 23 was obtained from 3-benzoyl-4(R)-methoxycarbonyl-2,2-dimethylthiazolidine (13) by treatment with benzoyl peroxide in refluxing benzene whereas compound 24 was obtained from 13 by borohydride reduction. The stereochemistry of the isomeric sulfoxides 18a and 18b, obtained from 13 by treatment with m-chloroperbenzoic acid, was assigned by means of 1 Hmr spectroscopy. Reaction of the sulfoxides 18a and 18b under the Pummerer-reaction conditions afforded the rearranged product, 4-benzoyl-3(R)-methoxycarbonyl-5-methyl-3,4-dihydro-2H-1,4-thiazine (20). The chiral shift reagent, tris-[3-(trifluoromethylhydroxymethylene)-d-camphorato]europium(III), was used to confirm the enantiomeric purity of the key intermediates and the product nucleosides. The carbon-13 nmr spectra of the key compounds are reported.