.1 Synthesis Of Research. Kaitocephalin, And Halipeptin A 2.cui / Amino Acid Catalyzed Alkenyl Iodide And Amide Coupling Reactions

Halobios are rich source of species, which are occupying about eighty percent ofearth species. Halobios also contain many earth life-forms incomparable, structurallyunusual, biologically active compounds, accounting for the differences of entironmentbetween halobios and earth life-forms as well as the relativity of marine biologicalchain. These compounds exhibit a variety of biologically activities, includinganticancer, antivirus, antitumor, anti-inflammatory and immunosuppressive action.They are some good medical precursors, which provide many model structures for theresearch and development of new drugs. In the first chapter of this thesis, we discuss the synthesis of Kaitocphalin, thefirst natural antagonist of AMPA/KA receptor, which isolated from marine alga in1997 by Japanese chemists. Start from L-glutamate, by reduction of amide, couplingwith allylsilane, we obtained the coupling product 13a, which reacted with (S)-Garneraldehyde providing the key intermediate 20. The compound 20 was converted intotarget molecule in 2% overall yield and 25 steps. Halipeptins are a novel 17-membered cyclic depsipeptides, which isolated fromthe new metabolites of marine sponge. In the second chapter of this thesis, wedemonstrated how to synthesis two unnatural amino acid fragment of Halipeptin A,name as N-methyl-δ-hydroisoleucine (N-MeOHIle) and α-methylserine. TheN-methyl-δ-hydroisoleucine (N-MeOHIle) fragment was constructed from the2-propynol in 8% overall yield and fifteen steps. The preparation of α-methylserinefragment was achieved from L-serine according to the literature in 23% overall yieldand five steps. Construction of N-methyl-δ-hydroisoleucine (N-MeOHIle) fragmentwas also attempted by allylation of proline-derived oximes. Enamides are special structures of many natural products, and very usefulintermediate for preparation of heterocycles and amino acids. In the third chapter ofthis thesis, we described a CuI/N,N-dimethylglycine-catalyzed coupling reaction ofvinyl halides with amide or carbamates. This reaction worked at room temperature to80 C, giving a verity of enamides in good to excellent yields. o...