부산대학교 도서관

New synthetic methods that enable rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. In this thesis, novel saturated heterocycles were targeted as C(sp3)-rich motifs to enrich existing pharmaceutical compound libraries. Initially, the synthesis of 2,2-disubstituted saturated nitrogen heterocycles, as 2-aryl proline analogues, is described. These products are synthesised through an N-H insertion of diazo compounds followed by one-pot cyclisation using mild base. The use of the same method to access 4- to 7-membered scaffolds is shown. The flexibility of the methodology is demonstrated by application to drug and natural product functionalisation. The utility of the products is shown by various important derivatisation reactions. Subsequently, the 4-membered azetidine products, synthesised by N-H insertion and cyclisation, are ring expanded to 6-membered 1,3-oxazinan-2-one products. Through exploration of the scope and mechanism of this 4- to 6-membered ring expansion a new methodology is developed for generating new leads for drug discovery. Finally, the N-H insertion of diazo compounds is coupled with a new enantioselective cyclisation reaction to synthesise enantioenriched spiroazetidines. This cyclisation step makes use of a new asymmetric phase transfer catalyst to achieve high er. A range of spiroazetidines are synthesised and the mechanism of the asymmetric phase transfer catalysis is discussed. A summary of specific conclusions and future work can be found at the end of each chapter. The final section provides experimental details.