The Biosynthesis of Tropane and Tobacco Alkaloids in Datura and Nicotiana Transformed Root Cultures

Organic chemistry, Plant sciences

Watson, Alan Boyd

University:University of Glasgow

关键词: Organic chemistry, Plant sciences;   

Others  :  http://theses.gla.ac.uk/78313/1/11008045.pdf

来源: University of Glasgow

【 摘 要 】

The biosynthesis of tropane and tobacco alkaloids has been extensively studied since the 1950's. Their importance is due to two main reasons: (i) use in medicine e. g. scopolamine, and; (ii) mis-use in society e.g. nicotine and cocaine. The advent of transformed root cultures (hairy root cultures) has allowed the expansion of these studies. The introduction of this thesis contains descriptions of tropane alkaloid structure and occurrence, tobacco alkaloid structure and occurrence, pharmacology of tropane alkaloids, pharmacology of tobacco alkaloids and finally, the aims of the project. A critical review of the biosynthesis of the tropane and tobacco alkaloids is presented in conjunction with a simplified description of the production and manipulation of transformed root cultures. Putrescine is incorporated into the carbon skeleton of (-)-hyoscyamine and (-)-scopolamine in the Datura plant species and (-)-nicotine in the Nicotiana plant species. It has been used as the starting block to study the biosynthesis of (-)-hyoscyamine and (-)-scopolamine and, in analogue form to study the effect on the biological systems of interest. Enantiomerically labelled putrescines, (R)-[2-2H]- and (S)-[2-2H]putrescine were synthesisd in order to study epoxide ring formation in the biosynthesis of (-)-scopolamine. The powerful technique of 2H n. m. r. spectroscopy was used to examine this biosynthetic step. These results are presented in Chapter Five. The enantiomerically labelled putrescines, (R)-[1-2H]- and (S)-[1-2H]putrescine were synthesised in order to study the biosynthesis of the tropane ring. The use of 2H n. m. r. spectroscopy was used to examine this biosynthetic step, firstly, in hygrine and secondly, in (-)-scopolamine. These results are presented in Chapter Six. The biosynthesis of anabasine in Nicotiana transformed root cultures was examined by the feeding experiments with (R)-[1-2H]- and (S)-[1-2H]cadaverine and analysis by 2H n. m. r. spectroscopy. This experiment has determined the optical purity of anabasine in Nicotiana transformed root cultures. These results are presented in Chapter Seven. Various analogues of putrescine were synthesised and administered to Datura and Nicotiana transformed root cultures. Their effect on the production of the natural occurring alkaloids was examined. In addition the selectivity of the enzymes involved in tropane and tobacco alkaloid biosynthesis was studied. They were also supplied for enzymic studies on the oxidation of putrescine derivatives by Diamine Oxidase.