An efficient enzyme-catalyzed kinetic resolution: large-scale preparation of an enantiomerically pure indole-ethyl ester derivative, a key component for the synthesis of a prostaglandin D2 receptor antagonist, an anti-allergic rhinitis drug candidate

Autor: Rob D. Larsen, Ralph P. Volante, Michel Journet, Ali Shafiee, Mirlinda Biba, Edward J. J. Grabowski, Anthony O. King, Jean-François Marcoux, Dalian Zhao, Veena Upadhyay, Kevin R. Campos, Edward G. Corley, Richard D. Tillyer
Rok vydání: 2005
Předmět:
Zdroj: Tetrahedron: Asymmetry. 16:3094-3098
ISSN: 0957-4166
Popis: Three racemic esters including indole-ethyl ester 1 as well as its related derivatives 3 and 4 in Scheme 1, all synthetic intermediates for the preparation of chiral compound 5 , were used as substrates to evaluate the catalytic potentials of a panel of commercial enzymes for asymmetric hydrolysis. After an extensive evaluation of the conversion rates ( C ), enantiomeric excesses (ee) and enantioselectivity determination ( E ), lipase from Pseudomonas fluorescens was identified. This lipase catalyzed the asymmetric hydrolysis of racemic indole-ethyl ester 1 affording the desired enantiomerically pure intermediate 1 with 97% ee and an E value of 425. Indole-ethyl ester 1 , with the following attributes: being early in the synthetic scheme, showing resistance to racemization in the later chemical reactions as well as the possibility of the recycling of the unwanted enantiomer, was therefore selected for optimization and establishment of an enzyme-catalyzed reaction for the industrial-scale synthesis of the compound 5 , a drug candidate for the treatment of allergic rhinitis.
Databáze: OpenAIRE
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