2. Academic Validation
  3. First enantiospecific synthesis of a 3,4-dihydroxy-L-glutamic acid [(3S,4S)-DHGA], a new mGluR1 agonist

First enantiospecific synthesis of a 3,4-dihydroxy-L-glutamic acid [(3S,4S)-DHGA], a new mGluR1 agonist

  • Bioorg Med Chem Lett. 2000 Jan 17;10(2):129-33. doi: 10.1016/s0960-894x(99)00641-1.
P Dauban 1,  C de Saint-Fuscien,  F Acher,  L Prézeau,  I Brabet,  J P Pin,  R H Dodd
Affiliations

Affiliation

  • 1 Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.
PMID: 10673095 DOI: 10.1016/s0960-894x(99)00641-1
Abstract

The first synthesis of one of the 4 possible stereoisomers of 3,4-dihydroxy-L-glutamic acid ((3S,4S)-DHGA 3), a natural product of unknown configuration, is described. The synthesis is based on the Lewis acid catalyzed reaction of benzyl alcohol with a D-ribose-derived 2,3-aziridino-gamma-lactone 4-benzyl carboxylate (6). Preliminary pharmacological studies showed that (3S,4S)-3 is an agonist of Metabotropic Glutamate Receptors of type 1 (mGluR1) and a weak antagonist of mGluR4 but has no discernible activity with respect to mGluR2. This activity profile can be rationalized by fitting extended conformations of (3S,4S)-3 in proposed models of each of these receptor subtypes.

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