Synthesis of Hypermodified Nucleosides Related to Phenylalanine Transfer Ribonucleic Acids.

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(1)An improved synthesis of the key intermediates for the synthesis of [R-(R*, S*)]- and [S-(R*, R*)]-beta-hydroxywybutines, the most probable structures for the minor base from rat liver tRNA^<Phe>, has been achieved by the Wittig reaction between 1-benzyl-7-formylwye and the phosphorane derived from (R)- 2-[(methoxycarbonyl)amino]-3-(triphenylphosphonio)- propanoate, followed by methylation, 0S0_4 oxidation, and cyclo-condensation with COCl_2 in the presence of pyridine. (R*, R*)-beta-Hydroxywybutine and its diastereomer, which were required for the determination of the optical purity of the chiral bases by means of chiral HPLC, were conveniently prepared through pyrolysis of the cyclic carbonate followed by NaBH_4 reduction and catalytic hydrogenolysis. The samples of [R-(R*, S*)]- and [S-(R*, R*)-beta-hydroxywybutines were thus shown to be optically pure.(2)The synthesis at the nucleoside level started with the Vilsmeier reaction of 3-[2,3,5-tris-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]wye and proceeded through the Wittig reaction with (R)-2-[(methoxycarbonyl)-amino]-3-(triphenylphosphonio)propanoate, methylation with trimethyl-silyldiazomethane, 0s04 oxidation, cyclocondensation with triphosgene, and catalytic hydrogenolysis. Chromatographic separation of the resulting diastereomeric mixture and subsequent deprotection afforded the two desired nucleosides for the first time.(3)it has been revealed that the rate of isomerization of l-benzyl-4-methyl-4,9-dihydro- 1H-imidazo[1 ; 2-alpha]purin-9-ones in 0.1 M MeONa-MeOH at .25*C increases with increasing electron-withdrawing nature of the 7-substituent and that the reactivity is further promoted by the intramolecular hydrogen bond between the carbonyl group at the 9-position and the 7-substituent.