Enantioselective Enzymatic Synthesis of ( R)‐Phenyl Alkyl Esters and Their Analogue Amides using Fatty Acids as Green Acyl Donors.

• Published in: ChemistrySelect
• Main Authors: Benamara, Nour ElHouda, Merabet‐Khelassi, Mounia, Lakoud, Samia Guezane, Aribi‐Zouioueche, Louisa, Riant, Olivier
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2021
• Subjects: Rugosa; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1002/slct.202103831; https://onlinelibrary.wiley.com/doi/pdf/10.1002/slct.202103831; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/slct.202103831

Abstract An efficient enantioselective synthesis of a set of ( R ) ‐ phenylalkylesters and their analogues amides via enzymatic acylation of 1‐phenylethanol ( rac‐ 1 ) and 1‐phenylethanamine ( rac‐ 2 ) using carboxylic acids with different chain‐lengths as green acyl donor is reported. Three lipases are used: Candida antarctica B immobilized on acrylic resin ( CAL‐B ) and two free lipases: Pseudomonas cepacia ( PCL ) and Candida rugosa ( CRL ). The CAL‐B shows an excellent selectivity during the acylation of rac ‐ 1 without restriction due to the acyl carbon chain‐length, the ( R ) ‐ esters ( 1 a – 1 f ) were obtained enantiopures (ee up to 99 %). For the first time, the PCL catalyzed O ‐acylation allows smoothly to ( R )‐( 1 d – 1 f ) with high selectivity (E⋙200) is described. The conversions increase with the length of the carbon‐chain of the acyl donor (28.7 %≤C≤40 %). The CRL shows less selective and provided the ( R ) ( 1 b – 1 e ) with 77 %≤ee p ≤86.4 %. Due to its high thermostability, the CAL‐B is used for the N ‐acylation of rac ‐2 and provides access to enantioenriched ( R )‐fatty amides ( 2 d – 2 f ) (60.7 %≤ee p ≤74.4 %) and the remained ( S )‐2 with ee s >91 %.