A 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]. / Andrew Chakane 2018
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/25878 |
| Date | January 1992 |
| Creators | Jungmann, Christa Maria |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
Page generated in 0.002 seconds