Design And Synthesis Of Anti-mycobacterium Tuberculosis Resistant Compounds And The Aldol Reactions Of Hemiacetals

This thesis includes two sections.1 、 Design and synthesis of compounds as potent inhibitors of drug-resistant Mycobacterium tuberculosisTuberculosis is a chronic infectious disease caused by Mycobacterium tuberculosis in the Mid-20 th century, the TB has been effectively controlled with the discovery of a large number of anti-TB drugs. But in recent years, tuberculosis incidence and mortality increased year by year because the emerging of drug-resistant Mycobacterium tuberculosis from drug abuse and other reasons. That’s urgent to discovery a number of new and more effective anti-TB drugs for the treatment of tuberculosis.Currently, there are a variety of drugs into clinical trials, in which the ethambutol analogs SQ 109 can enhance the other anti-TB drugs active in combination therapy and shorten the treatment time.Two series of ethambutol derivatives have been prepared as potential drug resistant Mycobacterium tuberculosis inhibitors in this thesis. These compounds exhibited efficient anti-TB activity. The compound 50 a, 70 e, 70 f showed the most potent inhibitory activity(MIC=4 μg/ml for drug-resistant Mycobacteriun tuberculosis) These findings expanded the chemical diversity of drug-resistant Mycobacterium tuberculosis inhibitors.2. The aldol reaction of hemiacetalA wide variety of natural products and chemical drugs include the tetrahydrofuran ring, especially in anti-tumor and antiviral drugs, which is an important functional group in the drug activity. At present, Polysubstituted tetrahydrofuran ring has being studied widely, but seldom of the 3-mono-substituted tetrahydrofuran ring is reported. It’s of great significance to discovery simple,efficient and highly selective 3-mono- substituted tetrahydrofuran ring.In the past 20 years, the organic catalysis has become one of most important in organic chemistry areas to built the special configuration of the chiral compounds because of its mild reaction conditions, cheap catalyst and the reaction is green. Organocatalytic asymmetric Aldol reaction is an important method for C-C bond formations in drug synthesis.In this thesis, the target compounds of chiral 3-mono-substituted tetrahydrofuran can be obtained by a two step transformation using hemiacetal as a substrate and proline as the catalyst, and the enantioselectivity and diastereoselectivity of products are good. These reactions prove the good applicability of hemiacetal with various electrophilic substrates.