Graduation Year

2004

Document Type

Dissertation

Degree

Ph.D.

Degree Granting Department

Chemistry

Major Professor

Bisht, Kirpal S.

Keywords

Sophorolipids, Beta-lactam, Imperanene, Enzymatic kinetic resolution, Biocatalysis

Abstract

The employment of enzymes and whole cells has been important in many industries for centuries. However, it is only in the last 30 years that the use of enzymes for the synthesis of high-value fine chemicals has enjoyed increasing popularity. In fact, esterases and lipases are used almost routinely these days to provide optically active building blocks for the construction of imaginative new routes to chiral target molecules. The major topic of this work describes the utilization of enzymes (namely lipases) in the synthesis and modification of natural and non-natural compounds.

Chapter 1 outlines the strengths and weaknesses of the most widely used enzyme systems and a description of a brief summary on the state of the art of biotransformations with special emphasis on the general applicability and reliability of various reaction types is described. Chapter 2 describes the enzymatic resolution of various 3-acetoxy-4-aryl-substituted azetidin-2-ones. Following screening of enzymes, such as Novozym-435, PS-30, PPL and AYS the best conditions were a phosphate buffer with PS-30 as the enzyme. The resulting products were the (3S, 4R)-3-hydroxy-4-aryl-substituted azetidin-2-ones and the unreacted (3R, 4S)-3-acetoxy-4-aryl-substituted azetidin-2-ones. Reactions generally occurred with high conversion and high selectivity. In Chapter 3, the regioselective transesterifications and hydrolysis of peracylated sophorolipid (SL) derivatives catalyzed by lipases was investigated.

It was confirmed from the detailed spectral analysis of the products that transesterification failed to furnish any free hydroxyls on the sophorose ring. Instead, transesterification took place on the methyl ester located at the carboxylic end of the 17-hydroxyoctadecenoic acid chain attached to the C-1' position of the sophorose ring. In Chapter 4, the chemo-enzymatic syntheses of enantiomerically pure R and S imperanene from vanillin are described. The key step entails the asymmetrization of a prochiral diol using lipase PS-30. The resulting monoacetate has enantiomeric excesses of >97%. Biocatalysts represent a new class of chiral catalysts useful for a broad range of selective organic transformations. It is stating the obvious to say that biocatalysis is not a panacea for synthetic organic chemistry.

However, advances over the past thirty years mean that it would be a serious mistake not to consider the employment of a biocatalyst, in, perhaps, the key step in a sequence of transformations that turn a cheap starting material into an expensive fine chemical.

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