Lipase‐Catalysed Enzymatic Kinetic Resolution of Aromatic Morita‐Baylis‐Hillman Derivatives by Hydrolysis and Transesterification. (29th September 2022)

• Record Type: Journal Article
• Authors: Mathebula, Nompumelelo P.; Sheldon, Roger A.; Bode, Moira L.
• Is Part Of: Chembiochem. Volume 23:Number 21(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-09-29
• Subjects: enzymatic kinetic resolution -- lipases -- molecular modelling -- Morita-Baylis-Hillman -- Mosher derivatives -- PCL; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.202200435
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: Acylated Morita‐Baylis‐Hillman (MBH) adducts were synthesised and subjected to enzymatic kinetic resolution (EKR) by hydrolysis employing various lipase enzymes: from P. fluorescens, P. cepacia (PCL), C. antarctica A (CAL−A), C. antarctica B (CAL−B) and Novozyme 435. In a number of instances enantiopure Morita‐Baylis‐Hillman acetates or butyrates and their corresponding hydrolysed MBH adducts were obtained with ee values of >90 %, at ca. 50 % conversion, corresponding to enantiomeric ratio (E) values of >200. Enantioselective transesterification reactions on MBH adducts was achieved using acyl anhydrides in THF or the greener organic solvent 2‐MeTHF in the presence of CAL−A. This is the first report of successful lipase‐catalysed EKR of aromatic MBH adducts by transesterification in organic medium. Abstract : Acetate and butyrate esters of aromatic Morita‐Baylis‐Hillman adducts have been resolved by enzymatic hydrolysis using a range of lipases: P. fluorescens lipase, P. cepacea lipase (PCL), CAL−A, CAL−B and Novozyme 435. The best enantiomeric ratio was observed for the butyrate derivative of the p ‐cyanophenyl MBH adduct. Transesterification of aromatic MBH adducts in organic solvent in the presence of an acyl donor has been demonstrated for the first time.