Chemical and enzymatic synthesis of amino acids and penicillins /
| Main Author: | |
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| Other Authors: | , , |
| Format: | Thesis Book |
| Language: | English |
| Published: |
1988.
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| Subjects: | |
| Online Access: | Link to OAKTrust copy |
| Abstract: | The use of enzymes as synthetic organic catalysts in the preparation of several chiral compounds is demonstrated. The enzymatic approach toward amino acid synthesis provides a new route to a variety of amino acids, aldehydes, and lactones when a nicotinamide cofactor-regenerative scheme with horse liver alcohol dehydrogenase and glutamate or leucine dehydrogenase is incorporated. The application of one- and two-phase systems in preparative enzymatic synthesis has been successfully demonstrated. Analysis of these systems based on experimental results and model studies indicates that the two-phase reaction is demonstrably better in most aspects considered. Amino diacid monoesters which serve as chiral synthons and as substrates for their subsequent incorporation in penicillin precursors are prepared enzymatically. Pig liver esterase, procine pancreatic lipase, α-chymotrypsin, Candida cynlindracea lipase, cholesterol esterase, and papain have all been used for the successful synthesis of the monoesters. Modelling of some of the substrates using energy minimized conformations allows for the rationalization of regioselectivities observed during the hydrolytic reactions. The preparation of penicillin precursors has been achieved through the combined use of chemical and enzymatic synthesis. Chymotrypsin and, to a lesser extent, C. cylindracea lipase are used in peptide synthesis. The new penicillin precursors generated are subsequently tested for their biological activity with iso-penicillin N synthetase. Chiral α-hydroxy and α-amino acids and aldehydes are prepared by the enantioselective and enantiospecific oxidation of diols and amino alcohols. The alcohols are oxidized by horse liver alcohol dehydrogenase with preferential formation of the L-isomer. Concommitant in situ oxidation of the aldehyde to the acid is carried out by a nonspecific aldehyde dehydrogenase. The biologically important methyl group donor s-adenosylmethionine is synthesized both chemically and enzymatically. Optimization of its chemical and enzymatic synthesis and improvement of its chemical stability to decomposition and racemization are the focus of this part of the study. Although having a low chemical yield, the enzymatic synthesis is ascertained to be the method of choice because of its simplicity and high optical yields of the desired epimer. A newly developed HPLC method allows for the rapid isolation of (-)-AdoMet in optically pure form. Mechanisms for the chemical decomposition and epimerization are discussed and presented. Data on the stability is decomposition by both acid and base catalysis, and epimerization by pyramidal inversion is presented. |
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| Item Description: | Typescript (photocopy). Vita. "Major subject: Chemistry." |
| Physical Description: | xvii, 224 leaves : illustrations ; 29 cm |
| Bibliography: | Includes bibliographical references (leaves 207-223). |