The research in this thesis covers two areas: (i) combinatorial chemistry involving the synthesis of solid-phase supported reagents and approaches to compound libraries; and (ii) synthetic approaches and purification methods for heterocyclic
guanidines. A range of solid-phase supported reagents were prepared and an analytical protocol for such materials was established. Products contained mainly aldehyde, alcohol, oxime and nitro functional groups and were synthesised from Merrifield resin with good levels of substituent loading. These reagents were then used in further synthesis. Five
combinatorial libraries were synthesised comprising of ureas, thioureas, sulfonamides, dihydropyrimidines and cyano acrylic methyl esters. Reactions achieved were in moderate to good yield and the use of scavenger resins, as an alternative route, in some cases, proved successful.
As a result of purification problems associated with solution-phase methods, the synthesis of cyclic guanidines was investigated with the aim of producing such compounds by solid-phase methodologies. Three solid-phase approaches to producing cyclic guanidines were attempted; however the cleavage step proved unsuccessful in each case. Silylation was then carried out successfully with crude products in good yield; unfortunate! y purification resulted in derrotection of the alcohol.
The reaction of guanidine and epoxide in the presence of base yielded cyclic guanidines. A five-membered guanidine heterocycle was produced in a maximum of 33 % yield, from several reactions, and greater than 90 % purity. In a similar approach 7-membered monomeric and dimeric cyclic guanidines were synthesised. Additional equivalents of epoxide and base were added after initial alkylation of the guanidine to bias the products formed. It was hoped that the dimer species could be elucidated further by achieving greater yields and could also be useful for further synthetic
approaches. The biasing was promising and dimeric material was produced in greater amounts, such that-1 equivalent ofreagent gave a ratio of 70: 30, 2 equivalents gave 37:63 and 3 equivalents gave 22: 78 of monomer to dimer.