Asymmetric Syntheses of Enantiopure 4-Substituted Pipecolic Acid Derivatives

• Published in: European journal of organic chemistry Vol. 2001; no. 12; pp. 2385 - 2389
• Main Authors: Agami, Claude, Bisaro, Fabrice, Comesse, Sébastien, Guesné, Sébastien, Kadouri-Puchot, Catherine, Morgentin, Rémy
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.06.2001; WILEY‐VCH Verlag GmbH; Wiley; Wiley-VCH Verlag
• Subjects: Amino acids; Asymmetric synthesis; Bioorganic chemistry; Chemical Sciences; Chemistry; Chemistry, Organic; Natural products; Physical Sciences; Science & Technology; ANTAGONIST; THROMBIN; amino acids; ALPHA-AMINO-ACIDS; natural products; (2S,4R)-4-HYDROXYPIPECOLIC ACID; POTENT; asymmetric synthesis; bioorganic chemistry; DIELS-ALDER REACTION; ASPARTIC ACID; CHEMISTRY; (2R,4S)-4-HYDROXYPIPECOLIC ACID
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/1099-0690(200106)2001:12<2385::AID-EJOC2385>3.0.CO;2-Z

(2R,4R)‐4‐Methylpipecolic acid and (2S,4R)‐4‐hydroxypipecolic acid, two biologically active amino acids, were synthesized using the same strategy. A third amino acid, obtained in a protected form, was also obtained in the same way. The key step of these syntheses involves an intramolecular ene‐iminium cyclization which occurs with complete stereoselectivity. The resulting exocyclic double bond can react in a diastereoselective way to afford pure lactones, which can then be efficiently converted into the amino acids.