Synthesis of Staphylococcus Aureus Type 5 CPS Repeating Units

PS1 Poster session 1 Odd numbers
Location (hall): 
Start/end time: 
Monday, July 1, 2019 - 15:45 to 17:15

Sizhe Li1, G.A. van der. Marel1, J.D.C. Codée1

1Leiden Institute of Chemistry, Leiden, The Netherlands

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.

Strategy for synthesis of CPS types

  1. . Hagen, J. H. M. Van Dijk, Q. Zhang, H. S. Overkleeft, G. A. Van Der Marel, J. D. C. Codée, Org. Lett. 2017, 19, 2514–2517.
  2. J. P. Yasomanee, S. Visansirikul, P. Pornsuriyasak, M. Thompson, S. A. Kolodziej, A. V. Demchenko, J. Org. Chem. 2016, 81, 5981–5987.
  3. S. Visansirikul, S. A. Kolodziej, A. V. Demchenko, J. Org. Chem. 2019, 84, 216–227.
  4. I. A. Gagarinov, T. Fang, L. Liu, A. D. Srivastava, G. J. Boons, Synthesis of Staphylococcus Aureus Type 5 Trisaccharide Repeating Unit: Solving the Problem of Lactamization, 2015.
  5. B. Hagen, J. H. M. Van Dijk, Q. Zhang, H. S. Overkleeft, G. A. Van Der Marel, J. D. C. Codée, Org. Lett. 2017, 19, 2514–2517.