Lipase-catalyzed stereoresolution of long-chain 1,2-alkanediols: A screening of preferable reaction conditions

• Published in: Journal of molecular catalysis. B, Enzymatic Vol. 116; pp. 60 - 69
• Main Authors: Parve, Jaan, Reile, Indrek, Aid, Tiina, Kudrjašova, Marina, Müürisepp, Aleksander-Mati, Vallikivi, Imre, Villo, Ly, Aav, Riina, Pehk, Tõnis, Vares, Lauri, Parve, Omar
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-06-2015
• Subjects: 1,2-Alkanediols; Diesters; Lipases; Spontaneous acyl migration; Stereoselective methanolysis; 1,2-Alkanediols; Spontaneous acyl migration; Stereoselective methanolysis; Lipases; Diesters
• ISSN: 1381-1177; 1873-3158
• DOI: 10.1016/j.molcatb.2015.03.006

•Lipase-catalyzed methanolysis of diesters affords enantiomeric (S)-1,2-alkanediols.•Crystallization of (S)-enantiomer from reaction mixture complements the resolution.•The influence of solvent, acyl group, nucleophile, temperature and lipase was studied.
Scalable lipase-catalytic method for the kinetic resolution of long-chain 1,2-alkanediol enantiomers via stereoselective cleavage of esters was developed. The influence of lipase, reaction medium, nucleophile, temperature and the structure of the acyl group on the reaction velocity, the stereopreference and the stereoselectivity of the deacylation was studied. In addition, the rate of the spontaneous intramolecular migration of different acyl groups was determined for the intermediate 2-monoesters. The acyl group migration may diminish the apparent stereoselectivity of the two-step process if fast migrating acyl groups are used. It was found that the migration rate of different acyl groups differs by up to two orders of magnitude, being faster for acetyl and isobutyryl and much slower for butyryl and benzoyl groups.
The best results were obtained by the sequential methanolysis of bis-butyryl-1,2-alkanediols in an acetonitrile/methanol mixture catalyzed by Candida antarctica lipase B (CALB) at 20°C, affording (S)-1,2-alkanediols. Stereo- and chemoselective crystallization of the deacylated (S)-1,2-alkanediols from the reaction mixture complements the enzymatic process improving the stereochemical purity to up to ee>99.8%. (R)-1,2-Alkanediol 2-monoesters were separated from the mother liquor and enriched stereochemically by repeated incubation with CALB, then separated, hydrolyzed with alkali and crystallized to afford (R)-alkanediols of ee>99.8%.