Efficient synthesis of monophosphoryl lipid A mimetic RC-529

Abstract

An efficient approach for the facile synthesis of a potent vaccine adjuvant RC-529 is described. The synthetic strategy relies on the flexible use of orthogonal protecting groups, which makes it possible to accomplish selective phosphorylation, glycosylation and acylation, respectively. In addition, the use of readily cleaved 2-naphthylmethyl (Nap) ether and allyl esters as permanent protecting groups greatly facilitates the final global deprotection steps to obtain pure RC-529. This work will contribute to the synthesis of lipid A and its derivatives.

Graphical Abstract

Keywords:

• Glycolipid
• synthesis
• adjuvant
• lipid A
• RC-529

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [22077130 to T.L.], Shanghai Pujiang Program [20PJ1415800 to T.L.], Science and Technology Commission of Shanghai Municipality [20ZR1467900 to T.L.], Shanghai Municipal Science and Technology Major Project (T.L.), and National Major Scientific and Technological Special Project for “Significant New Drugs Development” [2019ZX09302014 to Q.S.].

Notes on contributors

Tiehai Li

Prof. Tiehai Li received his Ph.D. degree in Chemical Biology at Nankai University in 2012. Then he joined Prof. Peng George Wang’s group at Georgia State University for postdoctoral training. Since 2015, he worked with Prof. Geert-Jan Boons in Complex Carbohydrate Research Center at University of Georgia. At the end of 2019, he started his independent research career at Shanghai Institute of Materia Medica, Chinese Academy of Sciences. His major research interests focus on developing efficient methods and strategies for the synthesis of biologically important oligosaccharides and glycoconjugates, and the design and synthesis of carbohydrate-based drugs and vaccines.