The use of stereospecifically-labeled phenylpropanoid compounds to determine the steric course of key reaction steps in the biosynthesis of taxol, hyoscyamine, and cycloheptyl fatty acids

The literature describes a variety of mutases which catalyze structural changes within one molecule, so that the net catalysis of these reactions results in only a regio- and/or stereospecific difference between the substrate and the product. The stereochemistry of a majority of mutase-catalyzed reactions has been examined, and the information gained has provided a basis for understanding their mechanisms.;The chapters in this thesis will discuss the stereochemical course of three separate mutases that rearrange their respective phenylpropanoid substrate into a unique isomeric product. Chapter 1 will focus on taxol biosynthesis in Taxus brevifolia and more expressly will discuss the results on the discovery of phenylalanine 2,3-aminomutase activity in crude cell-free extracts of T. brevifolia. The enzyme activity is responsible for the stereospecific conversion of S-phenylalanine into the obligatory R-;Chapter 2 will describe the stereochemical analysis of the littorine mutase activity found in transformed root cultures of Datura stramonium. This mutase reaction converts the phenyllactate ester alkaloid, littorine, to its tropate ester alkaloid regioisomer, hyoscyamine. The stereochemistry of this reaction was determined unambiguously using stereospecifically deuterated phenyllactic acid.;Finally, Chapter 3 will report a biologically unusual ring expansion, initiated by mutase-like rearrangement involving the aromatic ring and the methylene carbon of phenylalanine. The cycloheptylundecanoic fatty acid which ultimately results via this ring expansion is essential in forming the cell membrane of the thermophilic bacterium, Alicyclobacillus cycloheptanicus.