Study On Synthetic Methodology Of Small Molecule Heterocyclic Compounds

Discovery of lead compounds is one of critical processes in drug research and development. It is inevitable for looking for lead compounds before anyone medicinal chemistry project was started. Therefore, it can increase the discoverable probability of lead compounds with pharmacological activities by developing efficient synthetic methods of privileged structures and rapidly building high-quality compound library cooperated with increasing perfect high-throughput screening technology. According to a-methylene-γ-butyrolactone natural products with a broad range of biological activities, a novel selectively synthetic method of (E)-and (Z)-isomer was designed in this paper. In another part of this paper, two new and efficient synthetic methods of benzofused sultam were developed via C-H activation according to sulfa drug molecules. Rapidly primary building of these two structural compounds libraries by these methods was finished.a-methylene-γ-butyrolactone structural motif consist in many natural products which possessing a wide range of remarkable biological activities, such as antiviral, antibacterial, anticancer activities and so on. Z-and E-isomers exit in this structure because of different groups substituted on the C=C double bond. From the summuray of natural products cantaining a-methylene-γ-butyrolactone, we found that E-isomer of some compounds are active, on the contrary, Z-isomer of other compounds are active. Therefore, in order to avoid Leakage screen, selective synthesis of these two isomers is critical for next activity screen. In this paper,46different a-methylene-y-butyrolactones from propiolic acid derivatives and alkenes were synthesized via palladium-catalyzed tandem reaction in one-pot. Selective cis-and trans-chloropaladation of alkynes and palladium chloride were achieved by possibly controlling the concentration of Cl ion in reaction system, and the desired compounds were gained in good yields and high selectivities.Sulfonamide derivatives were researched widely for half a century as antibacterial drugs. Recently, an increasing number of medicinal chemists started to research sultam in order to looking for more novel Sulfonamide structures, and some biological activities were found which were not preformed in previous linear sulfa drugs. In this paper, Rh-catalyzed sulfonic acid and sulfonamide directed otho olefination of arenas were developed. Solvents, temperature and different groups were discussed, and finally27desired sulsam derivatives werr synthesized by these two methods.