The introduction briefly reviews the nicotinic activity of nicotine analogues and general aspects of the nicotine pharmacophore. The thesis is concerned with the synthesis and biological activity of nicotine analogues in which the pyridine ring is replaced by a substituted oxazole-, thiazole-, or oxadiazole- ring. The use of a new 1,3-dipolar cycloaddition reactions involving tautomeric generation of the 1,3-dipole is exploited. These reactions involve imines derived from heterocyclic aldehydes and amino acid esters. Imine formation labilises the $\alpha$-proton of the amino acid esters and promotes a formal 1,2-hydrogen shift generating 1,3-dipoles. These 1,3-dipoles are generated as reactive intermediates and their existence is inferred from the structure of the cycloadducts obtained when the imines are heated in a non-polar solvent in the presence of dipolarophiles. The stereochemistry of these adducts has been investigated by nmr spectroscopy. When imines are prepared from aryl and heterocyclic aldehydes and diethyl aminomalonate, the labile $\alpha$-proton is activated by two ester groups and this results in a strong tendency for the imines to dimerize by an anionic 4$\pi$ + 2$\pi$ cycloaddition. The resulting imidazolidines were found to be thermally labile at ca. 110$\sp\circ$ when they undergo a retro-1,3-dipolar cycloaddition generating a 1,3-dipole and a neutral imine. Few examples are known where retro-1,3-dipolar cycloadditions generate 1,3-dipoles in which the central atom is protonated(UNFORMATTED TABLE OR EQUATION FOLLOWS)$$\vbox{\halign{\hfil#&\hfil#\cr +& $-$\cr (i.e. X = Y& $-$ Z).\cr H&\hfil\cr}}$$(TABLE/EQUATION ENDS)If the thermal fragmentation is carried out in the presence of dipolarophiles such as N-phenylmaleimide, maleic anhydride and diethyl azodicarboxylate, the thermally generated 1,3-dipole can be trapped. Yields in these processes are typically 50-60% based on imidazolidine suggesting that some, at least, of the neutral imine is giving rise to the corresponding 1,3-dipolar species by tautomerism. The stereochemistry of these cycloadducts has been studied by nmr spectroscopy.