APPLICATIONS OF SUGAR NITRONES IN SYNTHESIS - THE TOTAL SYNTHESIS OF (-POLYOXIN-J())

A convergent synthesis of the peptidyl nucleoside antibiotic (inhibito r of chitin biosynthesis) polyoxin J (2) by coupling of 5-O-carbamoyl polyoxamic acid (3) and thymine polyoxin C (4) is described. These com pounds were prepared by chain elongation and amination of sugar-derive d aldehydes employing their nitrones as iminium derivatives and the fu ran ring as a masked carboxyl. Thus, the stereoselective addition of 2 -lithiofuran to the L-threose derived N-benzyl nitrone 5 followed by r eduction of the resulting hydroxylamine to amine, carbamoylation of th e free hydroxy group, and oxidative cleavage of the furan ring to the carboxylate group gave a protected derivative of 3 (30%). The same met hod was followed for the synthesis of the ribofuranosyl alpha-amino ac id nucleoside 4 (12.6%) starting from the D-ribose derived nitrone 6. The final coupling was performed by the N-hydroxysuccinimide active es ter method in DMSO with the Hunig base (i-Pr2EtNH) using a derivative of 3 and unprotected 4.