Jungmann, Christa Maria2018-10-232018-10-231992https://hdl.handle.net/10539/25878A Dissertation submitted to the Faculty of Science, University of the Witwatersrand, Johannesburg, in fulfilment of the requirements for the Degree of Master of Science.An outline of reported synthetic routes to the Lupine alkaloids, epilamprolobine [2] and lamprolobine [3] and a review of the use of vinylogous amides and urethanes as precursors for the synthesis of alkaloids are presented in Chapter 1. This is followed by a presentation of our strategy for synthesis of the two Lupine alkaloids. Vinylogous cyanamide intermediate 1- (3-hydroxypropyl) -2- cyanomethylenepiperidine [68] plays a key role in this strategy, since exploitation of its ambident nucleophilicity forms the central theme of this project, The successful route to the intermediate [68] involved the preliminary preparation of the tertiary thiolactam, 1-(2- ethoxycarbonylethyl)piperidine-2-thione [83][ by thiation of the secondary lactam 2-piperidinone [72] and conjugate addition at nitrogen with ethyl acrylate in a Michael reaction. Sulphur extrusion of the salt made from [83] and bromoacetonitrile and subsequent reduction of the ester group provided the pivotal vinylogous cyanamide intermediate. A number; of alternative routes based on 5- bromopentanoic acid [80], 1-allyl-2-piperidinone [73] and thiolactams [84J and [105] were unsuccessful. Cyclisation of the intermediate [68] was achieved by an intramolecular c-alkylative ring closure via the corresponding tosylate [l16] to forln an unsaturated functionalised quinolizidine [69]. Stereoselective carboncarbon double bond reduction and nitrile reduction resulted in the synthesis of two quinolizidines. lupinamine [11] and epilupinamine [112]. Further transformations led to the formation of the derivatives, N-acetyllupinamine [113] and N-acetylepilupinamine [114], and also to the target alkaloids, epilamprolcbine [2] and lamprolobine [3].enAlkaloids -- Synthesis.Plant metabolites.Botanical chemistry.Stereochemistry.Thesis