Structure and reactivity of wyosine (y-nucleoside) and its derivatives. Chemical, kinetic and spectroscopic studies
1988; Elsevier BV; Volume: 44; Issue: 4 Linguagem: Inglês
10.1016/s0040-4020(01)85908-1
ISSN1464-5416
AutoresC. Glemarec, Jinyi Wu, Gérald S. Remaud, Hervé Bazin, Mikko Oivanen, Harri Lönnberg, Jyoti Chattopadhyaya,
Tópico(s)HIV/AIDS drug development and treatment
ResumoWyosine-triacete 4 undergoes electrophilic formylation, iodination and bromination reactions exclusively at C7 while 2',3',5'-tris-O-(t-butyldimethylsilyl)wyosine (6), under a base-induced deuterium exchange reaction, forms a C2 -deuterio derivative 14. This clearly shows that the "right" imidazole in wyosine (1) and in its triacetate 4 is much more π-electron-rich (electrophilic) than the "left" imidazole part. pKa measurements and 15N-NMR spectroscopic studies of wyosine (1), its triacetate 4 and several of its C7-substituted derivatives shows that the preferential site (ca. 80%) of protonation in compound 4 is N5 and the N1 is only 20% protonated. A C7-electron-withdrawing substituent (-CHO), as in 7, however, promotes protonation mainly at N1. The N1-ribosylated isomer 15, prepared by the acid-catalyzed isomerization of 4, is more basic (pKa 3.10) than wyosine-triacetate 4 (pKa 2.36) which has been corroborated by the differrence of their 15N shifts between protonated and neutral species (Δδ). Furthermore, acidic depurination studies particularly with N1-ribosylated isomer 15 and its comparison with that of wyosine-triacetate 4 have shown that the latter undergoes depurination reaction only 7 times faster; it may therefore be assumed that the unusually enhanced rate of acidic hydrolysis of glycosidic bond in wyosine (1) and in its triacetate 4 is not primarily due to steric acceleration by its N4-methyl group, but due to electronic factors. Metal ion binding studies, using 15N-NMR spectroscopy, suggest that Mg2+ ion does not bind to the Y-base but to its phosphodiester function in the anticodon loop of tRNAPhe.
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