Efficient synthesis of an imidazole-substituted delta-amino acid by the integration of chiral technologies.
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.
Appleby
Ian
I
Dowpharma, Chirotech Technology, Ltd., A Subsidiary of The Dow Chemical Company, Cambridge, UK.
Boulton
Lee T
LT
Cobley
Christopher J
CJ
Hill
Catherine
C
Hughes
Mike L
ML
de Koning
Pieter D
PD
Lennon
Ian C
IC
Praquin
Céline
C
Ramsden
James A
JA
Samuel
Helen J
HJ
Willis
Niamh
N
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
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