Synthesis Two Natural Antibacterial Glycoconjugates And Their Derivatives

The oligosaccharides units of glycoconjugates have an important influence on their biological activity. At present, a great interest in the synthesis of glycoconjugates to elucidate the associations of oligosaccharides with disease mechanisms is raising. This research has accomplished the synthesis of two natural antibacterial glycoconjugates and their derivatives.Synthesis and antibacterial evaluation of natural oligorhamnoside and their analoguesThe rising incidence of infections caused by antibiotic-resistant bacteria has become a major concern for clinicians and the public health system. In the past several years, these types of infections have increased in severity, and their treatment has become far more complex and costly. Therefore, new prototype antibacterial agents with unique chemical structures, dissimilar toxicities, broad spectrum of activity and cross-resistances with present antibiotics are desperately needed. Oligosaccharides have the ability to control the microbial infection, thus they may be a good alternative of antibiotics. Thus, the total synthesis of a partially acetylated dodecanyl tetrarhamnoside derivative, cleistetroside-2, which was isolated from Cleistopholis patens and C. glauca and showed significant in vitro antibacterial activity against the Gram-positive bacteria, was achieved for the first time. To probe the SAR of these oligorhamnosides in more detail, cleistrioside-5 (28) which has almost equivalent antibacterial activity with cleistetroside-2 and its analogues (29-37) were synthesized and evaluated for in vitro antibacterial activity. And all the target compounds against gram-positive bacteria were evaluated by the agar dilution method described by the NCCLS. It should be noted that both cleistrioside-5 and compound 2 exhibited favorable antibacterial activity to vancomycin-susceptible Enterococcus faccalis, vancomycin-resistant Enterococcus faecium and streptococci with MIC of≤8μg/mL. The primary SAR showed the 2"-OAc of cleistrioside-5 were requisite for the antibacterial activity. Further study aiming to mechanism of action of cleistrioside-5 is in progress.Total synthesis of marine antimicrobial glycolipid caminoside BThe virulence mechanism of deadly pathogens such as Enteropathogenic Escherichia coli (EPEC) and Enterohemorragic E. coli 0157:H7 (EHEC) that are deadly for children and the elderly mainly depend on E. coli type III secretion system, while benign commensal strains do not. So components of this system might be good targets for novel antimicrobial agents and selective type III secretion system inhibitors are potential antimicrobials. The first total synthesis of caminoside B, a small-molecule type III secretion system inhibitor (IC50=20 M) isolated from the marine sponge Caminus sphaeroconia, was developed. This novel antimicrobial glycolipid was assembled in good yield via a'2+2+1'strategy based on stereocontrolled construction of the four glycosidic linkages. The major novelty of our work, with respect to the previously reported caminoside A, is that the the R-configured secondary alcohol of the aglycon has been stereoselectively constructed. Furthermore, we got the pure target natural isomer caminoside B, instead of the peracetate derivative, which could not offer the natural glycolipid for the acetyl can not be selectively removed in the presence of the butyryl group.