ENANTIOMERICALLY PURE DIMETHYL (2S)-N-(9-PHENYLFLUOREN-9-YL)-3,4-DIDEHYDROGLUTAMATE AS CHIRAL EDUCT - CHIROSPECIFIC SYNTHESIS OF (+)-5-O-CARBAMOYLPOLYOXAMIC ACID AND 3-ALKYLGLUTAMATES

We report here a short and efficient synthesis (four steps, 78% overall yield) of dimethyl (2S)-N-(9-phenylfluoren-9-yl)-3,4-didehydroglutamate (1) in enantiomerically pure form from L-glutamic acid. The C-C double bond in 1 was introduced by selective selenenylation-oxidation of dimethyl N-(9-phenylfluoren-9-yl)glutamate. 1 did not undergo loss of enantiomeric purity when stored for several weeks at room temperature, thus demonstrating the ability of the 9-phenylfluoren-9-yl (Pf) group to protect the highly acidic chiral center of 1 from racemization. The alpha,beta-unsaturated carboxyl group of 1 was selectively reduced with DIBAL. Carbamoylation of the resulting alcohol, followed by OsO4-mediated hydroxylation of the double bond and deprotection afforded (+)-5-O-carbamoylpolyoxamic acid, a component of the polyoxin family of antifungal antibiotics (>40 % overall yield from glutamic acid). 1 underwent lithium dimethyl cuprate addition with complete retention of chiral integrity, albeit in a nonstereoselective fashion, to give 3-methylglutamates and 3-methylpyroglutamates.