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Macrolide produced by Streptomyces the weak alkaline antibiotics are widely used in clinical respiratory tract infections, gastrointestinal infections and infections of the genitourinary system treatment. However, with the extensive application of antibiotics, especially the abuse of many bacteria produce resistance to macrolide antibiotics, which brought great difficulties to the clinical treatment. Therefore, the development of new anti-drug-resistant macrolide antibiotics has become a current drug research hotspot. The antibacterial mechanism studies have shown that: the role of macrolide antibiotics target located at the exit of the channel of the 50S subunit peptides, close to the peptidyl transferase center. When the macrolide antibiotic combined with the target, will plug the peptide channel, inhibition of protein synthesis, so as to produce an antimicrobial effect. Bacteria through a variety of mechanisms of macrolide resistance, the main mechanism for target modification: resistant carrying erm gene expression will produce methyl transferase methylation of A2058, which bacteria as a result the MLS B -type resistance. Therefore, based on the new target for the design of synthetic anti-drug-resistant macrolide antibiotics, is an important way to address bacterial resistance. Macrolide and ketolide antibiotics defects bacterial ribosomal 50S subunit A ~ P nucleotide, and A752 for the second target, design synthesis of a new anti-drug-resistant macrolide antibiotics in order to solve the problem of drug-resistant macrolide antibiotic resistance. According to the above-described design idea, this paper has a strong antibacterial activity and excellent pharmacokinetic properties of azithromycin as a lead compound, and the C-4 \structural modification, design and synthesis of a series of novel 15-membered macrolide derivatives by MS, IR, 1 HNMR 13 CNMR and other methods to determine the compound the structure established four series of compounds synthetic route, optimize the synthesis process, the mild reaction conditions, post-processing is simple, high yield paper using double dilution method determination of target compounds in vitro antibacterial activity antibacterial activity : (1) anti-susceptible strains activity: all the target compounds anti-susceptible S. pneumoniae good activity with clarithromycin and azithromycin comparable or similar (2) anti-drug-resistant activity: most of the compounds in the series A, B and C anti- M-type resistant Streptococcus pneumoniae A22072 strong activity, which compounds A1, B2, B4, B7, C6 and C11 anti-drug-resistant most active (MIC = 0.06μg/mL); C series compounds are MLS B -type resistant Streptococcus pneumoniae B1 has a good antibacterial activity (MIC ≦ 0.5μg/mL), wherein the C1 to C3, and a C6 ~~ C7 and C9 ~ C11 anti resistant strongest activity (MIC = 0.25μg / mL); compound A6, B4, B5, B7 and C7, mixed-type-resistant Streptococcus pneumoniae exhibit antibacterial activity (MIC are 2μg/ml) are summarized as follows according to the structure and the antimicrobial activity of the target compound, the structure-activity relationship : (1) a macrocyclic lactone nucleus to generate anti Susceptible must be active structure, urethane side chains in the introduction of the C-4 \ester side chain to the aryl sidechain resistant activity of the anti-M-type well (2) is introduced in the C-4 \bit introduced into the carbonate ring, can be maintained the activity of anti-Susceptible; when the C-4 \C-4 \
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