title: Dynamic kinetic resolution of 2,3-dihydrobenzo[b]furans: chemoenzymatic synthesis of analgesic agent BRL 37959.
abstract: An efficient asymmetric synthesis of (S)-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8 a) and (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (8 b) was established. Key to the success was the highly stereoselective enzymatic kinetic resolution of the corresponding methyl or ethyl esters that was further developed into a dynamic process. As a reliable and fast tool for analysing the enantiomeric excess, HPLC coupled with a CD detector was utilized. The route was completed by a Friedel-Crafts acylation of ethyl (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylate (7 c) followed by saponification leading to (S)-5-chloro-2,3-dihydrobenzo[b]furan-3-carboxylic acid (2), an analgesic agent.
authors: Institut für Bioorganische Chemie der Heinrich-Heine Universität Düsseldorf im Forschungszentrum Jülich, Jülich, Germany.
authors: Patrick
authors: P
authors: Bongen
authors: Jörg
authors: J
authors: Pietruszka
authors: Robert Christian
authors: RC
authors: Simon
mesh_terms: D000215:Acylation; D000700:Analgesics / Q000138:chemical synthesis*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry*; D055162:Biocatalysis; D002264:Carboxylic Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D004800:Enzymes, Immobilized / Q000737:chemistry; D004952:Esters; D005656:Fungal Proteins / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C576845:(S)-2,3-dihydrobenzo(b)furan-3-carboxylic acid; C576846:(S)-5-chloro-2,3-dihydrobenzo(b)furan-3-carboxylic acid; D000700:Analgesics; D001572:Benzofurans; D002264:Carboxylic Acids; D004800:Enzymes, Immobilized; D004952:Esters; D005656:Fungal Proteins; D008049:Lipase; C431349:lipase B, Candida antarctica