SYNTHESES OF 2-[(1S,3S)-1-AMINO-3-CARBOXY-3-HYDROXYPROPYL]-THIAZOLE-4-CARBOXYLIC ACID AND THE TRIPEPTIDE SKELETON OF NOSIHEPTIDE CONTAINING THE ACID

The stereoselective synthesis of an amino acid component called Fragment D, N,O-diprotected 2-[(1S, 3S)-1-amino-3-carboxy-3-hydroxypropyl]thiazole-4-carboxylic acid of a macrobicyclic peptide antibiotic nosiheptide, was achieved by two routes. The dipeptide, Fragment B-C, 2-[(Z)-1-(N, O-isopropylidene-L-threonylamino)-1-propenyl] thiazole-4-carboxylic acid was also synthesized by the thiazole ring formation from (Z)-2-(N, O-diprotected L-threonylamino)-2-butenethioamide with ethyl bromopyruvate. The coupling of two components by using a condensing agent gave the expected tripeptide 2, which is an important partial skeleton of the nosiheptide.