Studies towards the Synthesis of the Fluorescent Bases of Phenylalanine Transfer Ribonucleic Acids : Synthesis of 7-(2-Hydroxy-3-methylbutyl)wye, a Model for the Minor Base Isolated from Rat Liver

Abstract

Treatment of 1-benzyl-7-(hydroxymethyl)wye (8) with PBr₃ in the presence of Ph₃P gave the phosphonium bromide 9 in good yield, Heating 9 and Me₂ CHCHO (7) in MeOH in the presence of K₂CO₃ provided 1-benzyl-1, 4-dihydro-4, 7-dimethyl-6-(3-methyl-1-butenyl)-9H-imidazo[1, 2-a]purin-9-one (11), a positional isomer of the objective 1-benzyl-7-(3-methyl-1-butenyl)wye (5), as a major product. When the reaction was conducted in Me₂NCHO at -65°C using n-BuLi as base, a 7 : 2 mixture of (E)-and (Z)-5 was obtained in good yield. Nevertheless, neither the protected amino aldehyde 18 nor 21 gave the desired olefin under similar conditions, implying poor applicability of this method to the synthesis of the fluorescent bases of phenylalanine transfer ribonucleic acids (tRNAs^Phe).Compound 5 was alternatively synthesized by the Wittig reaction between 1-benzyl-7-formylwye (3) and Ph₃P⁺CH₂CHMe₂ I^- (4) in tetrahydrofuran as an equimolar mixture of the geometrical isomers in 50% yield. When the reaction was carried out in Me₂SO at room temperature using two equivalents each of NaCH₂SOMe and 4, the product, obtained in high yield, was (E)-11. The use of an equimolar amount of the base afforded (E)-5 in 26% yield. Oxidation of (E)-5 with OsO₄ followed by hydrogenolysis over Pd-C gave 7-(2-hydroxy-3-methylbutyl)wye (2), a model for the minor base from rat liver tRNA.^Phe.