The four acetylatedd-aldose diethyl dithioacetals (1a-d) were treated with bromine to give the corresponding, unstable 1-bromides (2a-d), which were immediately condensed with 6-chloro-9-(chloromercuri)purine (3) to furnish the respective, protected nucleosides (4a-d). Subsequent treatment with thiourea gave the crystalline 6-mercaptopurine analogs (5a-d) which, upon deacetylation in butylamine-tetrahydrofuran, gave the free, acyclic-sugar nucleosides (6a-d)- With the exception of the arabino derivative 4b, the 6-chloropurine derivatives were mixtures of 1′-epimers. Crystallization of the acylated 6-mercaptopurine derivatives afforded single 1′-epimers for 5a-c; 5d remained an epimeric mixture. A positive Cotton effect for both the ribo and arabino analogs 5a and 5b, and a negative Cotton effect for the xylo derivative 5c, suggested the (1′R) configuration for 5a and 5b, and the (1′S) configuration for 5c. Proof of the stereochemistry at C-1 (as well as proof of derivatization at N-9 of the purine ring) was afforded by X-ray crystallographic analysis of the arabino derivative 5b, which was demonstrated to have the (1′R) configuration. Use of the Generalized Heterocycle Rule also supported the stereochemical attributions at C-1′ for the remaining compounds. The arabino derivative 5b adopts an extended, planar, zigzag conformation of the side chain in solution, as well as in the crystalline state, whereas the ribo (5a) and xylo (5c) derivatives exist in solution as non-extended, sickle conformations; the lyxo analog (5a) was found to be a mixture of 1′-epimers, both of which adopt in solution an extended, planar, zigzag arrangement of the sugar chain. © 1979.
