A concise, asymmetric synthesis of (2R,3R)-3-hydroxyaspartic acid

Abstract

3-Hydroxyaspartic acid and its derivatives are found both in the free form and as peptide constituents in various microorganisms and fungi. Considering the biological importance of this amino acid and its potential utility as a multifunctional building block in organic syntheses, we have developed a short-step, asymmetric synthetic route to a strategically protected 3-hydroxyaspartic acid derivative in enantiopure form. The key steps in the synthesis involve, Sharpless asymmetric aminohydroxylation of commercially available trans-ethyl cinnamate, and, utilization of the phenyl group as a masked carboxylic acid synthon towards construction of the complete structural framework of the title compound.

Application of asymmetric Sharpless aminohydroxylation in total synthesis of natural products and some synthetic complex bio-active molecules

“…Consequently, acetonide protection, oxidative degradation of the phenyl and removal of the protecting groups provided enantiopure hydrochloride salt of (2R,3R)-3-hydroxyaspartic acid 90 (Scheme 21). 102 The vancomycin group of antibiotics 103 are of attention to synthetic chemists because of the structural diversity and the clinical signicance of these compounds. 104 Ristocetin A 93 has structural aspects that are analogous to vancomycin, however ASAH reaction of olens is a useful approach for asymmetric synthesis of N-masked amino alcohol derivatives.…”

“…Consequently, acetonide protection, oxidative degradation of the phenyl and removal of the protecting groups provided enantiopure hydrochloride salt of (2 R ,3 R )-3-hydroxyaspartic acid 90 ( Scheme 21 ). 102 …”

Structural insights into the substrate stereospecificity of d-threo-3-hydroxyaspartate dehydratase from Delftia sp. HT23: a useful enzyme for the synthesis of optically pure l-threo- and d-erythro-3-hydroxyaspartate

“…Various effective methods for the preparation of 3-hydroxyaspartate as a racemate or an individual stereoisomer have been reported (Kaneko and Katsura 1963;Antolini et al 1997;Cardillo et al 1999;Khalaf and Datta 2008). It is of notable interest to develop a synthesis method for L-THA due to the obvious demand for its derivative L-threo-β-benzyloxyaspartate (L-TBOA) in the field of neuroscience as a potent blocker of EAAT subtypes (Shigeri et al 2004;Shimamoto 2008).…”