Thesis (Ph. D.)--University of Wisconsin--Madison, 1985. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 191-198).

Bochum, Universiẗat, Diss., 2000.

In part I of this thesis are described the structural determinations of sitsirikine, dihydrositsirikine and isositsirikine, three new alkaloids from Vinca rosea Linn. Sitsirikine, C₂₁H₂₆O₃N₂, and dihydrositsirikine, C₂₁H₂₈ O₃N₂, were isolated as an inseparable mixture, which was shown by hydrogenation studies to be comprised of an olefin and its dihydro derivative. The formation of formaldehyde upon ozonisation of the mixture, and of propionic acid in a modified Kuhn-Roth oxidation of dihydrositsirikine demonstrated that, sitsirikine possessed a vinyl group. Both sitsirikine and dihydrositsirikine gave mono-acetates, and the N.M.R. data indicated that primary hydroxyl groups were present in the original alkaloids. A methyl ester function suggested by spectral evidence was established by hydride reduction of dihydrositsirikine to a diol. Since the diol, yielded an acetonide, it was inferred that dihydrositsirikine possessed a β-hydroxy-ester unit. The U.V. spectrum of dihydrositsirikine was characteristic of an indole chromophore, which the mass spectrum showed to be part of a tetrahydro-β-carboline system. Dehydrogenatioh afforded a compound with a flavocoryline-type U.V. spectrum, and this suggested that sitsirikine was a relative of the tetracyclic corynantheine class of alkaloids. This was confirmed by conversion of dihydro-corynantheine into dihydrositsirikine. The structure of the related indole alkaloid isositsirikine, C₂₁H₂₆O₃N₂, was determined by a similar series of reactions. Ozonolysis yielded acetaldehyde, which authenticated the ethylidene group indicated by the N.M.R. spectrum. Acetylation afforded a mono-acetate, whose N.M.R. spectrum suggested that isositsirikine had a primary hydroxyl function. A methyl ester was established by hydride reduction to a diol, which formed an acetonide and hence showed the presence of a β-hydroxy-ester unit in the original alkaloid. Since dehydrogena-tion of dihydro-isositsirikine yielded flavocoryline, a tetracyclic structure very similar to that of sitsirikine could be postulated for isositsirikine. Part II is concerned with the chemistry of cleavamine, a scission product, of the Vinca alkaloid catharanthine. Treatment of catharanthine with aqueous acid in the presence of a reducing agent, led to the isolation of descar-bomethoxycatharanthine, cleavamine and two epimeric dihydro-cleavamines. A tentative mechanism for the reaction is proposed, which can account for the formation of these compounds. Reduction of catharanthine in glacial acetic acid provided carbomethoxy-dihydrocleavamine. Mercuric acetate oxidised this compound to a mixture of two immonium ions, both of which underwent transannular cyclisations. One of the ions gave the known Iboga alkaloids coronaridine and dihydrocathafanthine, whereas the other afforded pseudo-vincadifformine - a synthetic analogue of the known Vinca alkaloid vincadifformine. The structure of pseudo-vincadifformine was determined by conversion into compounds which had U.V., I.R., N.M.R. and mass spectra completely analogous to the corresponding derivatives of vincadifformine. Similar transannular cyclisations to the above are postulated in the scheme advanced by Wenkert for the biogenesis of Iboga and Aspidosperma alkaloids, and the significance of our results with regard to this theory is duscussed. The formation of coronaridine and dihydrocatharanthine in the reaction constituted partial syntheses of these alkaloids, and the potential use of transannular cyclisations in laboratory syntheses of Iboga and Aspidosperma alkaloids is also considered. / Science, Faculty of / Chemistry, Department of / Graduate

In part A, a much sought synthesis of the calycanthaceous alkaloids is described. Oxidative dimerization of N- methyltrytamine afforded dl- chimonanthine and meso-chimonanthine, and dl- calycanthine was produced by subsequent acid-catalyzed rearrangement of the carbon skeleton through a tetraminodialdehyde. As the suggested biosynthesis of these alkaloids is represented as occurring by an oxidative dimerization of N- methyltryptamine (itself a natural product) the very direct synthesis described is a biosynthetic model. The discovery of meso-chimonanthine in an extract of Calycanthus f1oridus is also reported and is the first natural calycanthaceous alkaloid with this stereochemistry to be discovered. As folicanthine and calycanthidine are N-methyl chimonanthines and this methylation has been reported, a synthesis of chimonanthine also represents a formal synthesis of these alkaloids. A proposal for the structure of hodgkinsine, the remaining calycanthaceous alkaloid, is made. A number of synthetic by-products are also described. In part B evidence for the mono-terpenoid origin of the nine or ten carbon non-tryptophan derived portion of the indole alkaloids is presented. The monoterpene, geraniol- 2- ¹⁴C, was administered to Vinca rosea cuttings and the Aspidosperma- type alkaloid, vindoline, was isolated and shown by Kuhn-Roth degradation to be labelled at C-5 as predicted by theory. Feeding experiments with mevalonic acid- 2- ¹⁴C are also described. / Science, Faculty of / Chemistry, Department of / Graduate

Thesis (Ph. D.)--University of Chicago, Department of Chemistry, December 2002. / Includes bibliographical references. Also available on the Internet.

Thesis (M. Phil.)--University of Hong Kong, 1981.

A novel technique was developed to immobilize plant cells. The cells are deposited on a surface of man-made fibrous material which provides for strong binding of the plant tissue biomass growing in the submerged culture. It was shown that the plant cells need to be fully viable for the attachment process to occur. / The scale-up of this technique to laboratory size specifically designed bioreactors was performed successfully. The cell immobilizing matrix was formed into a vertical spirally wound configuration to provide for a high immobilizing area-to-volume ratio (0.8-1.2 cm$ sp{-1}$). A modified airlift (riser-to-downcomer area ratio of 0.03 and vessel height-to-diameter (H/D ratio of 3) and a low H/D ($ sim$1.5) mechanically stirred vessel delivered the optimum bioreactor performance characterized by low foaming of the broth and highly efficient plant cell attachment and retention ($ geq$96%). / The growth of Catharantus roseus plant cells was investigated in these bioreactors. This process was found not to be mass transfer limited above minimal mild mixing and aeration levels ensuring sufficient supply of nutrients, especially oxygen (k$ sb{ rm L}$a $ sim$ 10-15 h$ sp{-1}$) to the immobilized biomass. / The gentle surface immobilization technique developed in this work did not hinder the biosynthesis potential of the SIPC. In fact, it appeared to induce a partial secretion of some valuable compounds into the culture medium. The mildness, easiness, efficiency, mass transfer characteristics, scale-up potential and biomass loading capacity (11-13 g d.w./L) of the surface immobilization technique make it superior to all other immobilization techniques used to culture plant cells. In addition, its bioreactor overall biomass concentration compares favourably to suspended plant cell concentrations attainable in bioreactors (15-20 g d.w./L).

No description available.

Catharanthus roseus est une plante médicinale produisant divers types d’alcaloïdes indoliques monoterpéniques (AIM) d’intérêt en santé humaine. Ainsi, les AIM dimères comme la vinblastine et la vincristine sont utilisés en chimiothérapie anticancéreuse et les alcaloïdes monomères de type hétéroyohimbine présentent diverses activités pharmacologiques. La fabrication de ces molécules dans la plante est fort complexe. Elle requiert un haut niveau de compartimentation tissulaire et subcellulaire et met en jeu plus d’une trentaine d’étapes enzymatiques, dont certaines sont encore très mal connues. Dans ce contexte, l’objectif de la thèse a consisté à élucider plusieurs étapes enzymatiques de la voie de biosynthèse des AIM. Nos travaux ont permis de caractériser de nouvelles isoformes enzymatiques de la famille des cytochromes P450 ainsi que les réductases qui leur sont associées. Ils ont abouti à l’identification de nouvelles déshydrogénases et mis en évidence, in planta, leurs interactions avec la strictosidine synthase suggérant une biosynthèse orientée vers les divers alcaloïdes de type hétéroyohimbine. Enfin, en ayant recours à l’ingénierie métabolique, un segment de la voie de biosynthèse a été transféré dans la levure Saccharomyces cerevisiae, lui conférant la capacité de bio-transformer la tabersonine en vindoline, l’un des deux précurseurs finaux des alcaloïdes dimères. / Catharanthus roseus is a medicinal plant producing various types of monoterpene indole alkaloids (MIA) with a great interest in human health. Dimeric alkaloids such as vinblastine and vincristine are used in cancer chemotherapy and monomeric heteroyohimbine alkaloids exhibit various pharmacological activities. The production of these molecules in the plant is very complex. It requires a high level of tissular and subcellular compartmentalization and involves more than thirty enzymatic steps, some of which are largely unknown. In this context, the aim of this thesis was to elucidate several enzymatic steps of the MIA biosynthetic pathway. Our work allowed us to characterize new enzyme isoforms of cytochrome P450 and their associated reductases. They also resulted in the identification of new dehydrogenases and highlighted their interactions with the strictosidine synthase suggesting a directed biosynthesis towards various heteroyohimbine type of alkaloids. Finally, engineered yeast containing a segment of the MIA biosynthetic pathway was able to convert tabersonine into vindoline, one of the two final precursors of the dimeric alkaloids.

Thesis (M.S.)--Mississippi State University. Department of Plant and Soil Sciences. / Title from title screen. Includes bibliographical references.