Ribose Conformations of Adenosine Analogs Modified at the 2', 3' or 5' Positions

Adenosine Analogs, Conformation, NMR The solution conformation of adenosine(/Oribosides modified at the 2', 3' or 5' position is derived from the analysis o f the HRNM R spectra of the ribose protons. The conformational equilibria of the furanoside rings are described by the two state N <-+ S model introduced by Altona and Sundaralingam. The new compounds studied are: 2'-thiobenzoyl-2'-deoxyadenosine, 3'-thio-3'-deoxyadenosine, 2'-chloro-2'-deoxyadenosine, 3'-chloro-3'-deoxyadenosine, 2'-bromo2'-deoxyadenosine, 3'-bromo-3'-deoxyadenosine, 2'-0-methyladenosine, j'-O-methyl-adenosine, 2/-deoxy-3'-0-methyladenosine, 5'-amino-5'-deoxyadenosine, 5'-acido-5'-deoxyadenosine, and 5'-chloro-5'-deoxyadenosine. The emphasis in this work is to study systematically the influence of the different substituents upon the conformational equilibria of the sugar. It is found that any substitution at the 2' posi­ tion stabilizes the S-conformer. An even more pronounced stabilization of the A-conformer in the 3' substituted analogs is observed. The equilibrium changes in these classes of compounds can neither be correlated quantitatively with electronegativity differences nor with sterical differ­ ences between the various substituents. Substitution at the 5' position influences the N <-> S equi­ librium only slightly, but has significant effects upon the conformational preferences of the exocyclic 5'-CH2R 3 group.