Dynamic Kinetic Resolution of Ethyl 1,2,3,4‐Tetrahydro‐β‐carboline‐1‐carboxylate: Use of Different Hydrolases for Stereocomplementary Processes

Abstract

Both enantiomers of 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylic acid have been prepared by dynamic kinetic resolution of the corresponding ethyl ester (±)‐1. CAL‐B‐catalysed hydrolysis of (±)‐1·HCl in NH4OAc buffer (pH 8.0, 30 °C) provided amino acid (R)‐2·HCl with 98 % ee and 90 % yield in 20 min. The hydrolysis with Alcalase in borate buffer (pH 8.0, 30 °C) showed S selectivity and the product (S)‐2·HCl was obtained with 60 % ee and 66 % yield in 45 h. The absolute configuration of (S)‐2 was determined by TDDFT electronic circular dichroism and optical rotation calculations.

Clara Immerwahr Award: T. L. Lohr / Head of the Chemical Division, Hungarian Academy of Sciences: F. Fülöp / JSPS 141st Committee on Microbeam Analysis Award: H.‐J. Freund / Distinguished Scientist, Chinese Academy of Sciences: M. T. Reetz

“…Fülöp's recent research has focused on enzymatic transformations, asymmetric syntheses, foldamer construction, and flow chemistry with respect to the development of pharmacologically active compounds and new synthetic methodologies. He has reported in the European Journal of Organic Chemistry on the dynamic resolution of ethyl 1,2,3,4‐tetrahydro‐β‐carboline‐1‐carboxylate, and in ChemPlusChem on the synthesis of nontoxic protoflavone derivatives …”

Clara‐Immerwahr‐Preis: T. L. Lohr / Vorsitzender des Fachbereichs Chemie der Ungarischen Akademie der Wissenschaften: F. Fülöp / JSPS 141st Committee on Microbeam Analysis Award: H.‐J. Freund / Auszeichnung der Chinese Academy of Sciences: M. T. Reetz

“…Fülöps Forschung umfasst enzymatische Umwandlungen, asymmetrische Synthese, Foldamere sowie Flusschemie für die Entwicklung pharmakologischer Wirkstoffe und neuer Synthesemethoden. Er veröffentlichte im European Journal of Organic Chemistry einen Beitrag über die dynamische Racematspaltung von 1,2,3,4‐Tetrahydro‐β‐carbolinen‐1‐carbonsäureethylester und in ChemPlusChem über die Synthese ungiftiger Protoflavon‐Dderivate …”

Catalytic Asymmetric Alkynylation of 3,4‐Dihydro‐β‐carbolinium Ions Enables Collective Total Syntheses of Indole Alkaloids

“…In addition, enzymatic kinetic resolution of THbC-1-carboxylates was reported. [16] However, access to enantioenriched C1-alkynyl THbCs has not been explored with these prior approaches,w hich might not be compatible with alkynes.…”