Enantioselective Total Synthesis of (1R,3S,4R,5R)-1-Amino-4,5-dihydroxycyclopentane-1,3-dicarboxylic Acid. A Full-Aldol Access to Carbaketose Derivatives

• Published in: Journal of organic chemistry Vol. 69; no. 7; pp. 2611 - 2613
• Main Authors: Battistini, Lucia, Curti, Claudio, Zanardi, Franca, Rassu, Gloria, Auzzas, Luciana, Casiraghi, Giovanni
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.04.2004; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Catalysis; Chemistry; Chemistry, Organic; Dicarboxylic Acids - chemical synthesis; Dicarboxylic Acids - pharmacology; Exact sciences and technology; Glutamic Acid - chemistry; Indicators and Reagents; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Receptors, Metabotropic Glutamate - agonists; Science & Technology; Stereoisomerism; RECEPTOR; HETEROCYCLIC SILYLOXY DIENES; D-FRUCTOFURANOSE; ANALOGS; EFFICIENT; AGONIST; Molecular rigidity; Intramolecular reaction; Glutamic acid; Agonist; Enantioselectivity; Nitrogen heterocycle; Ketose; Lactam; Organic siloxane; Glutamate receptor; Total synthesis; Aldol condensation; Pyrrole derivatives; Aldol; Amine; Aminoacid; Analog; Chirality; Cross reaction; Dicarboxylic acid; Chemical synthesis; Cyclopentane derivatives
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo035846a

The enantioselective synthesis of cyclopentanedicarboxylic amino acid 1, a novel rigid and functionalized l-glutamic acid analogue, has been achieved in 15 linear steps from silyloxypyrrole 3, utilizing l-glyceraldehyde 4 as the source of chirality. The key steps in the synthesis are three sequential aldol-based carbon−carbon bond-forming reactions:  two crossed vinylogous aldol additions (2 + 3 → 8 and 4 + 5 → 10 + 11) and one intramolecular silylative aldolization (6 → 7). En passant, the short syntheses of (2S)-2-hydroxymethylglutamic acid (16) and its (2R)-enantiomer ent-16, a potent metabotropic glutamate receptor agonist, have been achieved.