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Unusual conformational flexibility in N 1 ‐substituted uncommon purine nucleosides Crystal structure of 1‐allyl‐isoguanosine and 1‐allyl‐xanthosine

1992; Wiley; Volume: 297; Issue: 1-2 Linguagem: Inglês

10.1016/0014-5793(92)80315-8

1873-3468

Yen‐Chywan Liaw, Ji‐Wang Chern, Gwo‐Sen Lin, Andrew H.‐J. Wang,

Adenosine and Purinergic Signaling

Several new N 1 ‐substituted uncommon purine nucleosides, including doridosine (1‐methyl‐isoguanosine; m‐iG), 1‐allyl‐isoguanosine (a‐iG) and 1‐allyl‐xanthosine (a‐X), have been synthesized and tested as agonists for the adenosine receptors. Some have smooth muscle relaxant or negative chronotropic activities. The X‐ray crystal structure of these compounds has been determined at atomic resolution in order to understand the structure‐activity relationship. The structures were solved by direct methods and refined by full‐matrix least‐squares refinement procedure. The crystallographic parameters are: a‐iG, space group P 2 1 , a =10.573 (1) Å, b =21.955 (2) Å, c =14.360 (1) Å, β=110.65 (1)°, no. of 3σ Fo's=4585, R=0.047; a‐X, space group P 2 1 2 1 2 1 , a =16.015 (2) Å, b =16.239 (1) Å, c =5.3723 (5) Å, no. of 3σ Fo's= 1169, R=0.031. In the a‐iG crystal, there are 4 independent molecules (with different conformation) per asymmetric unit. While all 4 molecules adopt anti χCN glycosyl torsion angle, their riboses have 3 distinct puckers (C 2′ ‐exo, C 2′ ‐endo and C 1′ ‐exo). In contrast, the a‐X structure adopts a syn χCN glycosyl torsion angle, which is stabilized by an intramolecular hydrogen bond between the N 3 or purine base and the O 5′ of the ribose (in C 2′ ‐endo pucker). Both purine bases (a‐iG and a‐X) are mainly in the keto tautomer form. For the isoguanine base, the averaged N 1 –C 2 bond distance (1.42 Å) is significantly longer than that (1.375 Å) of the guanine base. For the xanthine base, N 3 nitrogen has an imino proton attached which is unambiguously located in the electron density map. The surprising flexibility in the ribose ring of these N 1 ‐substituted uncommon purine nucleosides suggests flat the ribose moiety may not participate in the binding of nucleoside to the adenosine receptors.