SYNTHESIS AND ABSOLUTE-CONFIGURATION OF WYBUTINE, THE FLUORESCENT MINOR BASE FROM PHENYLALANINE TRANSFER-RIBONUCLEIC-ACIDS

The phosphonium chloride 6 having an optically active amino acid moiety was synthesized from (S)-serine benzyl ester tosylate (2b) through a six-step route. The utility of 6 as a reagent for the Wittig reaction was exemplified in the olefination with benzaldehyde, affording the (E)-beta,gamma-unsaturated amino acid derivative 11 as a sole geometrical isomer. This new method of amino acid homologation was successfully employed for the first chiral synthesis of wybutine (1c), the minor base isolated from yeast phenylalanine transfer ribonucleic acids: the Wittig reaction between 6 and the tricyclic aldehyde 16 followed successively by methylation and catalytic reduction afforded 1c. Comparison of wybutine with synthetic 1c has unequivocally established that wybutine has an S configuration.