A synthesis of rhodotorulic acid

Abstract

A comparative study of the catalytic hydrogenation of benzyloxyamine hydrochloride ( 2a·HCl), benzyl benzohydroxamate ( 2b), and benzohydroxamic acid ( 3b) using PdC as a catalyst has disclosed that 2a·HCl smoothly undergoes the hydrogenolytic cleavage at both the benzyl—O and NO bonds, whereas 2b almost selectively suffers benzyl—O cleavage. The use of the benzyl group for protecting a hydroxamic acid function, suggested by the hydrogenolysis study, was embodied in the synthesis of rhodotorulic acid ( 1) starting with the reaction of 2a with bromide 5 to give 8. The key intermediate l- 9 was conveniently prepared by the selective, asymmetric deacetylation of 8 using Taka-diastase. Conversion of l- 9 into amino ester l- 13 through the N α-protected amino acid ( l- 11) and ester l- 12 and coupling of l- 11 with l- 13 yielded dipeptide ll- 14. Removal of the tert-butoxycarbonyl group from ll- 14 and cyclization of the resulting amino ester produced the penultimate benzyl hydroxamate ( ll- 15), which was debenzylated selectively with PdC and hydrogen to furnish 1.