Synthesis of Staphylococcus Aureus Type 5 CPS Repeating Units

The Staphylococcus aureus is a kind of Gram-positive bacterium that cause a wide range of diseases. Methicilin-resistant S. aureus (MRSA) has been being a huge challenge for anti-infection in therapeutics and clinic. Considering the lower efficacy of traditional antibiotic, the emergency requirements of novel anti-biotics is on the way. Thus, based on the mechanism that capsular polysccharides (CPS) in S. aureus might be employed as antigen in a protein conjugated vaccine, and most currently used antigens which are isolated from bacteria are carbohydrate compounds with specific structures, the design and synthesis of functionalized, well-defined carbohydrate-based vaccine has been drawing great interests in life science.

Most isolates of S. aureus contains two CPS, the type 5 and type 8 (figure). Both contains three rare monosaccharides; N-acetyl mannosaminuronic acid (ManNAcA), a 2-N-acetyl L-fucosamine (L-FucNAc) and a 2-N-acetyl D-fucosamine (D-FucNAc). The ManNAcA is linked to the position 4 of L-FucNAc by an β-glycosidic linkage, whereas the position 3 of D-FucNAc unit is connected to the L-FucNAc by an αmanner. Until now, there are limits of paper about the synthesis of CPS type 5 and type 8 [1-4]. In this work, based on the previous results on CPS in our team [1], we reported a total synthesis of modified structure of CPS type 5 including tricsaccharides, hexa-, nona- and dode- saccharides, in which the NHAc of D-FucNAc are replaced by NH3 for antibody evaluation. For the glycosylations of each building blocks, we employed a neighbouring participation NHTCA or NHTFA for construction of β-glycosidic linkage with spacer, and using TBS directing α-fucosylation to synthesis disaccharides, most importantly, the β-mannosylation has been being optimized by using two different ManNAcA systems. The project is still in progress, hereby we only present the preliminary results.