title: Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies.
abstract: Two methods to produce (2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid were investigated. Diastereoisomeric salt resolution, using the quinidine salt, gave the desired intermediate in 98% ee and 33% yield. Asymmetric hydrogenation of various substrates gave high conversions, with up to 83% ee. Integration of these two approaches via asymmetric hydrogenation of a quinidine salt substrate followed by crystallization provided the desired intermediate in 94% ee and 76% yield.
authors.affiliation: Dowpharma, Chirotech Technology, Ltd., A Subsidiary of The Dow Chemical Company, Cambridge, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Appleby
authors.forename: Lee T
authors.initials: LT
authors.lastname: Boulton
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Cobley
authors.forename: Catherine
authors.initials: C
authors.lastname: Hill
authors.forename: Mike L
authors.initials: ML
authors.lastname: Hughes
authors.forename: Pieter D
authors.initials: PD
authors.lastname: de Koning
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lennon
authors.forename: Céline
authors.initials: C
authors.lastname: Praquin
authors.forename: James A
authors.initials: JA
authors.lastname: Ramsden
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Samuel
authors.forename: Niamh
authors.initials: N
authors.lastname: Willis
mesh_terms: D000596:Amino Acids / Q000032:analysis / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D010421:Pentanoic Acids / Q000032:analysis / Q000138:chemical synthesis* / Q000737:chemistry; D011802:Quinidine / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: C507775:(2S)-5-amino-2-(1-n-propyl-1H-imidazol-4-ylmethyl)-pentanoic acid; D000596:Amino Acids; D007093:Imidazoles; D010421:Pentanoic Acids; C029899:imidazole; D011802:Quinidine