Enzymes as catalysts in synthesis of enantiomerically pure building blocks : secondary alcohols bearing two vicinal stereocenters

• Main Author: Liu, Rong
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: KTH, Organisk kemi 2005
• Subjects: enzyme; kinetic resolution; enantioselectivity; lipase; diastereoselectivity; epimerisation; metal-catalysed transformation; intramolecular alkylation; Other Basic Medicine; Annan medicinsk grundvetenskap; Antarc*; Antarctica
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-424

Enzymes as tools in organic synthesis have provided enormous advantages. This thesis deals with the applications of enzymes in the kinetic resolutions of racemic compounds. The stereochemistry of chiral compounds and the kinetics of α/β hydrolase lipases are presented. From a practical point of view, the handling of a large number of parameters that influences the kinetic resolutions, especially enantioselectivity (E-value) are systematically described. A variety of approaches employed for raising the yields to over 50% are additionally discussed. Methods for the preparation of synthetically useful chiral building blocks were developed in this thesis. Thus, resolution of secondary alcohols bearing two vicinal stereocentres are studied. These building blocks can serve as starting materials for the synthesis of various enantiomerically pure compounds for agrochemistry, pharmaceuticals, chemical industry, and particularly for the total synthesis of pheromones. Racemic 3-substitued 2-hydroxybutane derivatives were produced in fairly high diastereomeric purities by a variety of chemical approaches, such as epimerization, metal-catalysed asymmetric addition etc. Kinetic resolution of these racemates was achieved by enzyme-catalysed reactions. Two lipases, Candida antarctica lipase B and Pseudomonas cepacia lipase were found to be useful in acylations as well as hydrolyses. In the biotransformations studied, the presence and nature of the second vicinal stereocentre in the chiral secondary alcohols investigated seemed to be important, e.g. in terms of the efficiencies of sequential kinetic resolutions, and altering the selectivities as well. QC 20101020