Studies Towards the Synthesis of the Hypermodified Nucleoside of Rat Liver Phenylalanine Transfer Ribonucleic Acid: Improved Synthesis of the Base β-Hydroxywybutine.

An improved synthesis of the key intermediates (3 and 8) for the synthesis of β-hydroxywybutines [[R-(R * ,S * )]- and [S-(R * ,R * )]-4], 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 (1) and the phosphorane derived from (R)-2-[(methoxycarbonyl)amino]-3-(triphenylphosphonio)propanoate (10), followed by methylation, OsO 4 oxidation, and cyclocondensation with COCl 2 in the presence of pyridine. The racemic forms of β-hydroxywybutines [(R * ,S * )- and (R * ,R * )-4], which were required for the determination of the optical purity of [R-(R * ,S * )]- and [S-(R * ,R * )]-4 by means of chiral HPLC, were conveniently prepared through pyrolysis of the cyclic carbonate 3 followed by NaBH 4 reduction and catalytic hydrogenolysis. The samples of [R-(R * ,S * )]- and [S-(R * ,R * )]-4 were thus shown to be optically pure.