Study of the selective enzymatic acylation of multifunctional compounds : Application to pseudo-ceramide synthesis

• Main Author: Le Joubioux, Florian
• Other Authors: LIttoral ENvironnement et Sociétés (LIENSs), La Rochelle Université (ULR)-Centre National de la Recherche Scientifique (CNRS), Université de La Rochelle, Thierry Maugard
• Format: Doctoral or Postdoctoral Thesis
• Language: French
• Published: HAL CCSD 2012
• Subjects: Biocatalysis; O-acylation; Amino-alcohol; Lipase B; Candida antarctica; Organic solvent; Ionic liquid; Selectivity; Biocatalyse; Céramide; N-acylation; Amino-alcool; Solvant organique; Liquide ionique; Sélectivité; [SDV.SA]Life Sciences [q-bio]/Agricultural sciences; Antarc*; Antarctica
• Online Access: https://theses.hal.science/tel-00823900; https://theses.hal.science/tel-00823900/document; https://theses.hal.science/tel-00823900/file/2012_-_Le_-_Joubioux29850.pdf

Ceramides are lipids from the sphingolipide class derived from the N-acylation of a sphingoid base from a fatty acid. These lipids and their analogs are compounds of interest used as active components in pharmaceutical and cosmetic industries. Among biocatalysts able to synthesize this type of lipids, Candida antarctica lipase B appears to be the most appropriate enzyme for the production of "pseudo-ceramides" derived from amino-polyols. In this context, we have studied the acylation of amino-alcohol-like compounds catalyzed by Candida antarctica lipase B, keeping inmind a fundamental approach to expand the current knowledge on this subject. The first part of our work aimed to determine the reaction mechanisms and the enantio selectivity exhibited by Candida antarctica lipase B during O-acylation and N-acylation reactions, by conducting a kinetic study of mono functional compound acylation. In the following parts of our work, we performed a structurere activity study of the acyl acceptor substrate and evaluated the effect of the solvent used (organic solvent or ionic liquid) to determine the key factors influencing the chemo selectivity and the regio selectivity of the Candida antarctica lipase B-catalyzed acylation of polyfunctional amino alcohol compounds. Finally, starting from the knowledge acquired in the previous parts, we have developed and optimized an enzymatic process of “pseudo-ceramide” (O,N-diacylaminopropanediol) synthesis performed in a continuous packed-bed reactor. Les céramides sont des lipides de la classe des sphingolipides issus de la N-acylation d’une base sphingoide par un acide gras. Ces lipides et leurs analogues suscitent un grand intérêt comme composants actifs dans les industries pharmaceutique et cosmétique. Parmi les biocatalyseurs capables de réaliser la synthèse de ce type de lipide, la lipase B de Candida antarctica semble être l’enzyme la plus adaptée à la production de « pseudo-céramides » à partir d’amino-polyols. Dans ce contexte, nous avons abordé l’étude de l’acylation de ...