This thesis describes work conducted towards the preparation and application of C 2 symmetric guanidine containing catalysts and also studies directed towards the synthesis of model compounds of the marine natural product ptilomycalin A. The key reaction shared by these two themes is the Michael-like addition of guanidine to bis a, P-unsaturated ketones.
The following major achievements were made:
(1) A C2 symmetric tetracyclic guanidine catalyst was prepared from the double Michael addition of guanidine to (R)-6-oxo-2-(tert-butyldimethylsilyloxy)oct-7-ene. The a, P-unsaturated ketone precursor is prepared from ethyl (R)-(-)-3-hydroxybutyrate in a straightforward manner using a highly convergent synthetic strategy.
(2) Investigations were performed using this catalyst to assess its application in the conjugate addition of pyrrolidine to 2-(SH)-furanone. The reaction was conducted using .BF4-and .BPh4-counterions, and when compared to the uncatalysed reaction, 4.3-fold and 16.3-fold increases in reaction rate were observed respectively. On inspection of the adduct no enantioselectivity was observed.
(3) The preparation of a model compound of ptilomycalin A is also described. The key reaction in the synthesis is the addition-cyclisation of guanidine to a bis-enone system incorporating a phenyl ring and an alkyl spacer. The bis-enone is derived from 2-methyl naphthalene via a problematical ozonolysis step. Biological activity of the model compound and its precursors are described.
(4) The guanidine addition-cyclisation reaction was also employed in the synthesis of sulphur containing analogues of ptilomycalin A, however the yields obtained from this reaction were poor.