Lipase-Catalyzed Synthesis of Monoundecenoyl, Di-oligo(Ricinoleyl) Triacylglycerol and Chemical Conjugation of Acid-Functionalized Poly(Ethylene) Glycol Monomethyl Ether to Oligo (Ricinoleic) Acid to Enable the ‘Green’ Preparation of Amphiphilic Star Polymers
Date of Award
Master of Science
X Philip Ye, Svetlana Zivanovic
Chemo-enzymatic synthesis of unimolecular polymeric micelles (UPMs) is proposed for their potential utilization as drug delivery vehicles in dilute aqueous solutions. The UPMs are star polymers consisting of a hydrophobic core and hydrophilic corona. The core consists of multiple oligo(ricinoleic acyl) chains extending outwards from enzymatically synthesized triacylglycerols that contain one undecenoic acyl group and two oligo-(ricinoleic) acyl groups, joined together via free radical polymerization of the terminal double bond of undecenoic acyl groups. The corona consisting of poly(ethylene) glycol monomethyl ether (MPEG) will be conjugated to hydroxyl end groups of oligo(ricinoleic acyl) chains of the core molecule.
The objectives of this thesis will enable successful synthesis of UPMs with the structure given above. The first objective is the synthesis of 2-undecenoyl, 1,3-oligo(ricinoleyl) triacylglycerol. The second objective is conjugation of carboxylic acid derivative of poly(ethylene) glycol monomethyl ether (MPEG) to the hydroxyl end groups of the core’s oligo- (ricinoleic acid) chains, to enable the attachment of hydrophobic core and hydrophilic corona. A focal point of the work has been utilizing enzymatic catalysis in solvent-free systems, enabling the ‘green’ synthesis of the final product. Qualitative and quantitative analysis of the time course reaction and the reaction products were performed using analytical and preparative thin layer chromatography, high performance liquid chromatography, gel permeation chromatography, and proton nuclear magnetic resonance.
Candida antarctica lipase-catalyzed synthesis of triundecenoin via transesterification between undecenoic acid vinyl ester and glycerol, an important component of Objective.1, has been successfully achieved, at a > 95% yield. For the second sub objective, the Rhizomucor miehei lipase-catalyzed interesterification of triundecenoin and ricinoleic acid, has occurred at approximately 50-60% conversion yielding 1,3-ricinoleyl, 2-undecenoyl triacylglyceride(TAG) as the main product. As an alternative approach, the 1,3-selective Rhizomucor miehei lipasecatalyzed interesterification of undecenoic acyl groups with castor oil, had occurred at a similar yield (50-60% conversion). The third sub-objective, formation of di-oligo(ricinoleyl), 10- undecenoyl triacylglycerol was achieved using Candida antarctica lipase catalyzed esterification between ricinoleic acid and the triacylglycerol formed through Objective 1.2. Studies on conjugation of the terminal –OH group of ricinoleic acid and oligo-ricinoleic acid with poly(ethylene) glycol monomethyl ether (MPEG) were successful with 40-50% conversion.
Mannam, Vinay Kumar, "Lipase-Catalyzed Synthesis of Monoundecenoyl, Di-oligo(Ricinoleyl) Triacylglycerol and Chemical Conjugation of Acid-Functionalized Poly(Ethylene) Glycol Monomethyl Ether to Oligo (Ricinoleic) Acid to Enable the ‘Green’ Preparation of Amphiphilic Star Polymers. " Master's Thesis, University of Tennessee, 2009.