Highly Efficient Lipase Catalyzed Monoaminolysis Reaction of Diesters with Benzylamine

• Published in: Natural Product Communications
• Main Authors: Valerio-Alfaro, Gerardo, Castillo-Carrasco, Patricia Harumi, Castellanos Onorio, Olaya Pirene, Naranjos, Jorge Bautista
• Format: Article in Journal/Newspaper
• Language: English
• Published: SAGE Publications 2019
• Subjects: Complementary and alternative medicine; Plant Science; Drug Discovery; Pharmacology; General Medicine; Rugosa; Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1177/1934578x19859980; http://journals.sagepub.com/doi/pdf/10.1177/1934578X19859980; http://journals.sagepub.com/doi/full-xml/10.1177/1934578X19859980

Preparation of amides by biocatalyzed aminolysis reactions has greatly increased because these processes play an important role in the preparation of some pharmaceutical products and their intermediates. A highly efficient synthesis of malonic (5), succinic (6), and malic (8) monoamide esters by desymmetrization transformations (mono aminolysis reactions) of their diesters is presented. The immobilized lipase from Candida antarctica (CaL-B, Novozym 435) catalyzed the mono aminolysis of bifunctional compounds: diesters such as diethyl malonate (1), diethyl succinate (2), and ( R, S)-malate (3), leading to their corresponding monoamides (5), (6), and (8), respectively, with high conversions after a 24 hour reaction in the presence of an organic solvent. Increasing the solvent polarity from toluene, methyl t-butyl ether to dioxane led to an improved conversion. According to qualitative and quantitative GC-MS analysis, conversions of diesters (1), (2), and (3) into their mono amide esters were in the range 65%-97%. CaL-B was the best biocatalyst of the commercial lipases used, including those from Candida rugosa, Rhizomucor miehei, Carica papaya, and Pseudomonas cepacia. Likewise, a yield of 91% regioisomeric, but virtually racemic ( R,S)-mono amide (8) was obtained as the single product in dioxane.