Structure and reactivity of wyosine (y-nucleoside) and its derivatives. Chemical, kinetic and spectroscopic studies

Abstract

Wyosine-triacete 4 undergoes electrophilic formylation, iodination and bromination reactions exclusively at C 7 while 2',3',5'-tris- O -( t -butyldimethylsilyl)wyosine ( 6 ), under a base-induced deuterium exchange reaction, forms a C 2 -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. pK a measurements and 15N-NMR spectroscopic studies of wyosine ( 1 ), its triacetate 4 and several of its C 7-substituted derivatives shows that the preferential site (ca. 80%) of protonation in compound 4 is N 5 and the N 1 is only 20% protonated. A C 7-electron-withdrawing substituent (-CHO), as in 7 , however, promotes protonation mainly at N 1. The N 1-ribosylated isomer 15 , prepared by the acid-catalyzed isomerization of 4 , is more basic (pK a 3.10) than wyosine-triacetate 4 (pK a 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 N 1-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 N 4-methyl group, but due to electronic factors. Metal ion binding studies, using 15N-NMR spectroscopy, suggest that Mg 2+ ion does not bind to the Y-base but to its phosphodiester function in the anticodon loop of tRNA Phe.