Synthetic Studies On Dalesconol A,B, And Synthetic Methodology Development Of Polysubstituted Pyridines

The dissertation focuses on(i) synthetic studies on Dalesconol A, B(ii) Synthetic methodology development of polysubstituted pyridines.Dalesconol A, B which were isolated from fungi in mantis gut by Tan renxiang et al., possessed unique polyketide structure and biological activity of immunosuppressive. Because of these structural features and its biological activities, many studies have been devoted to its synthesis by us. Concerning of molecular symmetry, addition reaction of 3-methoxy-methyl benzoate 1-50 with two equivalents of naphthyl bromide 1-32 was attempted to get desired product 1-34. Subsequent 1-35 was oxidized by hypervalent iodide and transformed to the compound 1-54 with five membered ring. Then the targeted product was designed to be synthesized by sequential generation of seven membered ring, which could be derived from Michael addition and Friedel-Crafts reaction. However, the Michael addition of 1-54 was unsuccessful, which may caused by its steric hindrance. After selective reduction of diketone 1-54, several rearrangement reactions were investigated, however none of them gave desired product. Finally, we turned our attention to Stille coupling after obtainning 1-102, However, this approach was proved to be unsuccessful either.The second part of this thesis focused on the new synthetic methodology development of polysubstituted pyridines due to its important roles in natural products, active pharmaceuticals, functional materials, and synthetic intermediates. We have developed a facile synthetic protocol which proceeded via condensation of a α, β-unsaturated aldehyde and propargylamine to imine followed by isomerization to N-allenyl and 6π-3-azatriene electrocyclization to afford the corresponding polysubstituted pyridine. In addition, this is a reasonable methodology to the synthesis of Suaveoline,Norsuaveoline,Macrophylline,and Macrocaffrine. As part of our ongoing program aimed at synthesis of polysubstituted pyridines we developed an efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields. At last, a preliminary evaluation for the synthesis of polysubstituted pyridines via aza-Diels-Alder was also documented in this thesis.