The isolation and identification of pyrrolizidine alkaloids from various plant species from 1988 to May 1991 are reviewed and the alkaloids of two indigenous plant species, Senecio speciosus Willd and Senecio macrocephalus DC, were investigated. A brief review of the methods used for isolation and identification of pyrrolizidines is also given. S. speciosus was found to contain two new alkaloids, 7-senecioyl-9-sarracinylheliotridine and 7-isosarracinyl-9- sarracinyl-heliotridine, which were identified using highfield NMR techniques. A number of other alkaloids were tentatively identified using GC-MS. S. macrocephalus contains very little alkaloid, but a number of pyrrolizidine alkaloids were tentatively identified using GC-MS. Standard alkaloids for GC-MS work were obtained both by extraction from a number of plant species and by synthesis of simple monoester alkaloids. In this process the alkaloid neosarracine, previously described by GC-MS, was isolated and NMR data for this compound are reported for the first time. S. speciosus and S. macrocephalus are morphologically very similar and their counterparts in the Grahamstown district exhibit features characteristic of both species. This could be due to hybridization, genetic mutation or simple variation within the species. The alkaloids of four local plant populations were examined in order to collect taxonomic markers whereby it was hoped that the Grahamstown plants could be satisfactorily classified. Three of the plant populations were found to contain 7-senecioyl-9-sarracinylheliotridine and 7-angelyl-9-sarracinyl-heliotridine. One population was found to contain the known alkaloid retrorsine along with the new alkaloid 2-hydroxy-l, 2-dihydrosenkirkine. The alkaloidal fractions of all four populations were compared using GC-MS and NMR techniques. Tentative taxonomic conclusions were drawn.

The present investigation has involved a kinetic and mechanistic study of the thermal cyclization of 3-acetoxy-3-(2-pyridyl)-2-methylenepropanoate esters and related compounds to 2-substituted indolizines. Substrates for the kinetic study were prepared via the Baylis-Hillmann reaction of pyridine-2-carboxaldehydes with acrylate esters, acrylonitrile and methyl vinyl ketone. The resulting hydroxy compounds were then acetylated to afford the acetoxy derivatives, thermal cyclization of which gave the corresponding 2-substituted indolizines. The cyclization reactions was followed using 'H NMR spectroscopy and were shown to follow firstorder kinetics. The influence of the various substituents on the observed first-order rate constants has been examined and variable temperature studies have permitted evaluation of activation parameters for the formation of methyl indolizine-2-carboxylate and ethyl indolizine-2-carboxylate. An alternative route to 2-substituted indolizines via halogenated derivatives was explored and several halogenated 2-pyridyl derivatives were synthesised and their thermal cyclization to indolizines was attempted. Novel 5-methylindolizine-2-carboxamides were prepared as part of this investigation and dynamic NMR spectroscopy was used to study internal rotation about the amide N-CO bond in these compounds.

Indiana University-Purdue University Indianapolis (IUPUI) / The modification of brucine derivatives as chiral ligands and the use of a multifaceted chiral ligand, brucine diol, under different reaction conditions to produce various optical isomers is described. In Chapter 1, the generation of a number of brucine derivatives is described. Taking the advantage of brucine-diol’s excellent molecular recognition capability for multiple organic functional groups, we focused on the synthetic modifications of brucine-diol and the synthesis of brucine N-oxide. We also produced various brucine derivatives with different functional moieties in good yields and selectivities. In Chapter 2, we described the investigation of brucine N-oxide catalyzed Morita-Baylis-Hillman (MBH) reaction of alkyl/aryl ketones. Brucine N-oxide was used as a nucleophilic organic catalyst in the MBH reaction of alkyl vinyl ketone. In addition, asymmetric MBH reactions of alkyl vinyl ketones with aldehydes were investigated using a dual catalysis of brucine N-oxide and proline. In this dual catalyst system, proline was found to form iminium intermediates with electron-deficient aryl aldehydes, while the N-oxide activated vinyl ketones provided enolates through the conjugate addition. Our dual catalysis approach also allowed the development of MBH reaction of aryl vinyl ketones. In Chapter 3, brucine diol-copper complex catalyzed asymmetric conjugate addition of glycine (ket)imines to nitroalkenes is discussed. Stereodivergent catalytic asymmetric conjugate reactions for glycine (ket)imines with nitroalkenes were achieved using various chiral catalysts derived from a single chiral source, brucine diol. Both syn- and anti-conjugate addition products were obtained with high diastereoselectivity and enantioselectivity. In Chapter 4, enantiodivergent production of endo-pyrrolidines from glycine (ket)imines using brucine diol-copper complex is described. The [3+2] cycloaddition reaction of glycine imines and activated alkenes was performed to produce endo-pyrrolidines. The reversal of enantioselectivity was observed for endo-pyrrolidines between concerted and stepwise reaction pathways. The three new brucine derivatives produced in this study would potentially work as organocatalysts and chiral ligands with metal ion in asymmetric synthesis. The brucine diol-metal complex catalyzed reactions laid a good foundation for catalytic asymmetric reactions, where a single chiral source was used to control the absolute and the relative stereochemical outcomes of reactions. Understanding the molecular-level interactions between catalyst and substrates will provide insightful mechanistic details for the stereodivergent approaches in asymmetric catalysis.