The Study On Heterocyclic Compounds With Bioactivity

The thesis aims at the studies on four parts as following:Part I The design, synthesis and activity assay of Bcr-Abl kinase inhibitorsBased on the review of Bcr-Abl kinase inhibitors, we were interested in building a pharmacophore model. A series of compounds (including benzo[d]imidazole, benzo[b]thiophene and thiadiazol) as potential inhibitors were designed and synthesized. For the inhibitor assay, some compounds were observed to have inhibitory activities, and the result indicated benzo[b]thiophene derivatives showed good inhibitory activities.Partâ…¡Cu(â…¡)-catalyzed cyclization reactionBased on the review of synthetic method for furan derivatives, the intramolecular cyclization reaction of 2-propynyl-1,3-dicarbonyl compounds was explored. The reaction was performed using readily available materials (2-propynyl-1,3-dicarbonyl compounds), an inexpensive catalyst (Cu2+ salt) and ligand (PPh3) under very mild basic conditions in good to excellent yields. Then,5-methylene-4,5-dihydrofurans were easily converted into the corresponding furans under acidic conditions. The reaction provides a new approach to dihydrofurans in a direct, efficient and facile manner.Part III Asymmetric synthesis of N-terminal amino acid component of Nikkomycin BBased on the review of synthetic method for N-terminal amino acid component of Nikkomycin B, the asymmetric synthesis of N-terminal amino acid component of Nikkomycin B was explored.1,3-Dipolar cycloaddition reaction involving (E)-p-methoxycinnamyl alcohol and chiral nitrile oxide to construct the chiral isoxazoline was used as the key step. N-terminal amino acid component of Nikkomycin B was synthesized by subsequent functional group transformation. To our regret, the configuration is not consistent with the natural N-terminal amino acid component of Nikkomycin B.Part IV Asymmetric total synthesis of a-Lycorane Based on the review of synthetic method for Lycorane, the asymmetric synthesis of a-Lycorane was explored. Three stereogenic centers of a-Lycorane were effectively constructed with high diastereoselectivity and enantioselectivity via chiral thiourea catalyzing tandem Michael addition involving nitrostyrene and unsaturated ester. The key compound 101 was synthesized by subsequent functional group transformation, which established foundation for further asymmetric synthesis of a-Lycorane.