The first stereospecific synthesis of l-tetrahydrodipicolinic acid; a key intermediate of diaminopimelate metabolism

Abstract

L-Tetrahydrodipicolinic acid 1, a key intermediate of diaminopimelate metabolism has been prepared in 6 steps and 23% overall yield from L-allylglycine 4. The key step during this synthesis involves a base mediated cyclisation of dimethyl (2RS,6S)-2-[N-(benzyloxycarbonyl)-N-(p-tolylsulfonyl)amino]-6-[N-(benzyloxycarbonyl)amino]heptane-1,7-dioate 8 to give (2S)-N-(benzyloxycarbonyl)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid 9. ¹H NMR studies show this one pot transformation involves four steps; base elimination of toluene-p-sulfinic acid, intramolecular nucleophilic attack of the 6-benzyloxycarbonylamino group on the resulting imine, followed by hydrolysis of the esters and elimination of benzyl carbamate under acidic work-up to give the cyclic enamine 9.