Amino acids as chiral templates in the stereoselective syntheses of bioactive compounds: I. Stereoselective routes to 2,3-disubstituted piperidines. II. Synthetic studies on polyoxin J.

摘要

Part I. Enantiopure cis-2-phenyl-3-piperidinol is a commonly used synthon for the obtention of a potent class of neurokinin substance P receptor antagonists. Starting from (R)-phenylglycine, an efficient stereoselective synthesis of the above piperidinol structural core is reported. The key bond forming reactions in the synthetic pathway are (i) a chelation-controlled, stereoselective addition of an appropriate Grignard reagent to enantiopure N-Boc-phenylglycinal, and (ii) an oxidative cyclization of an appropriately functionalized alkenylcarbamate to form the desired piperidine structural scaffold.; Utilizing D-serine as a chiral template, the present research describes efficient and straightforward routes to cis- and trans-3-hydroxypipecolic acids in enantiopure form.; Part II. The complex peptidyl nucleoside antibiotic polyoxin J is a potent inhibitor of chitin synthase and exhibits impressive antifungal activity against various pathogenic fungi.; Employing (R)-serine and (R)-phenylglycine as strategic chiral platforms, the present research describes efficient protocols for the rapid construction of the furanosyl nucleoside amino acid core and the polyoxamic acid side chain of polyoxin J, respectively. Subsequent peptidic coupling of the above fragments and global deprotection completed the total synthesis of polyoxin J. (Abstract shortened by UMI.)