Studies towards the Synthesis of the Fluorescent Bases of Phenylalanine Transfer Ribonucleic Acids : Synthesis of 7-Methylwye Isolated from Extremely Thermophilic Archaebacteria

Abstract

Acid- or base-catalyzed acylation of 1-benzylwye (7) provided the 7-substituted derivatives 9, 10, and 11 in poor yields. Although the reactions of lithiated 7 with electrophiles gave the 2-substituted derivatives 14, 15, 17, 20, 21, and 22, lithiation of 1-benzyl-7-bromo-2-chlorowye (23) followed by treatment with Me₂CHCH₂CHO (13) successfully introduced a side chain at the 7-position to afford 1-benzyl-2-chloro-7-(1-hydroxy-3-methylbutyl)wye (24).Cyclization of 1-benzyl-3-methylguanine (5) with 3-bromo-2-butanone followed by catalytic hydrogenolysis afforded 7-methylwye (2b), the hypermodified base isolated from archaebacterial transfer ribonucleic acids. A more efficient route for the synthesis of 2b has been developed via a series of reactions : the Vilsmeier-Haack reaction of 7, reduction with NaBH₄, and catalytic hydrogenolysis over Pd-C.