Degree Name

Doctor of Philosophy


School of Chemistry


The main aim of this project was to develop a new synthetic methodology towards the total synthesis of the pentacyclic Stemona alkaloid stemocurtisine by first preparation of a tricyclic A-B-C ring precursor and then its tetracyclic ether derivative by an oxidative photolysis reaction.

In Chapter 2, we report our efforts to construct the A-ring of stemocurtisine using three different synthetic strategies. Synthetic strategy 1 failed due to unexpected ring opening of the hemiaminal product formed from the reactions between alkynyl Grignard reagents and a glutarimide derivative. Synthetic strategy 2 was not efficient due to the unsucessful conversion of a terminal alkynyltrimethylsilane to its corresponding propiolate methyl ester following the method of Kondo. Using synthetic strategy 3 we obtained the racemic desired ene-yne lactam A-ring derivative in 11 synthetic steps and in 12.1% overall yield from 4-pentyne-1-ol. In Chapter 3, we describe our successful method to construct the bicyclic A-B ring system of stemocurtisine following Mori’s ene-yne ring-closing metathesis procedure. The successful synthesis of the tricyclic A-B-C ring system of stemocurtisine is also discussed in this chapter. The synthesis of this tricyclic compound was achieved via a bromolactonization process using NBS/PhSeSePh followed by a base-catalysed elimination of the resulting bromolactone. Our attempts to reduce the resulting α,β-unsaturated lactone to its saturated derivative were not initially successful using the standard reducing reagents NaBH4/NiCl2 or NaBH4/CuCl. However, reduction of this α,β-unsaturated lactone using Mg/MeOH provided the saturated lactone derivative as a single diastereomer having the desired relative configuration at C-1, C-3a, C-11, C-11a and C-11b as stemocurtisine. Making the ether bridge of stemocurtisine was examined on two different substrates, a tricyclic hydroxyl piperidinone and a tricyclic hydroxy piperidine. Treatment of the piperidinone substrate under oxidative photochemical conditions gave an unexpected aldehyde byproduct having an O-acetyl hemiaminal structure. Detailed NMR analysis of this compound indicated that the piperidinone had undergone oxidative cleavage to give a bicyclic compound. The structure of this compound is only tenuous since the NMR spectroscopic and the MS spectromertic data were not consistent.

Chapter 4 reports on an alternative pathway to construct the A-B ring system and our attempts to make the A-B-C ring system of stemocurtisine. The key step of this approach involves the use of the borono-Mannich reaction to prepare a piperidinediene. A RCM reaction of this compound led to the corresponding pyrrido[1,2- a]azepine. Esterification of the hydroxyl group followed by epoxidation of this bicyclic compound resulted in the corresponding epoxide. Base-catalysed cylization was then attempted to convert this epoxide ester to a tricyclic compound. Under several reaction conditions this attempted cyclization was not successful and only the unreacted starting material was recovered.



Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.