The Synthesis of (2R)-Aziridine-2-carboxylic Acid Containing Dipeptides (original) (raw)

The synthesis of N-acyl-2-hydroxymethyl aziridines of biological interest

Tetrahedron Letters, 2004

A practical synthesis of the title compounds from protected amino acylazides is described. All the compounds might be considered as a novel class of dipeptide isostere precursors; they all induce lymphocyte proliferation and protein production as observed from preliminary biological tests.

A convenient synthesis of optically active 1H-aziridine-2-carboxylic acids (esters

Tetrahedron Letters, 1989

Optically active glycidic esters, prepared from allylic alcohols employing the Sharpless enoxidation. were treated with sodium azide. In a subseauent reaction with PPhl the azido alcohols thus obtained were converted into aziridine-2-carboxylic esters of high optical purity in good yields. Aziridine-2-carboxylic acids represent an interesting class of compounds since they may be. considered simultaneously as a-or B-amino acid derivatives. Little attention has been devoted so far to these carboxylic bE.e. ofepoxy alcohol. determinedfrom bxnvn optical rotations (entries a. e, g) or by 4W MHz 'H-NMR analysti of the Masher derivarive (entries b. c, dj. CDeterminedfrom brown optical rotation (entry g) or by 400 MHZ 'H.NUR analysis ofthe Masher derivative (entries a. b. c, d, GJ reaction medium, rhe oxazaphospholidines could be isolated. The compounds 6 were then subjected to a bulb-to-bulb distillation using a Kugelrohr apparatus, yielding the aziridinecarboxylic esters in moderate yields (method A) (entries a, e). When, however, the Staudinger reaction was performed in DMF or acetonitrile as the solvent, stirring at room temperature for 0.5 h followed by heating at about 80°C for a few hours afforded the aziridines in good yields without isolation of the intermediate oxazaphospholidines 4883 (method B) (entries b, c, d, f, g). The progress of the aziridine formation was monitored by TLC and infrared spectroscopy. Mixtures of isomeric azido alcohols were used for the Staudinger reaction. Method A permits only the use of rather small amounts of substrate and the distillation procedure is experimentally rather difficult. Method B is much preferred, since the reaction can be carried out on at least a 10 g scale without decomposition problems. The intermediate oxazaphospholidine derived from azido alcohol 5Ag was characterized by means of an X-ray diffraction analysis (figure 1). l5 This reveals that the epoxide opening with azide occurs with inversion of configuration. Thus after the Staudinger reaction we obtained a c&oxazaphospholidine from a truns-glycidic ester. All the oxazaphospholidines 6 showed a characteristic IR absorption near 3450 cm-' INH).