AI Article Synopsis
- Mucin-related tumor-associated carbohydrate antigens (TACAs) are promising targets for cancer vaccines, but creating a diverse library of these antigens is difficult.
- The study presents a new method for highly selective α-glycosylation using GalN-phenyl trifluoroacetimidate donors, resulting in high yields and robustness under mild conditions.
- The synthesis of various TACAs from a common intermediate, GalN-α-Ser, is achieved, with detailed mechanistic insights into the reaction provided through DFT calculations.
Article Abstract
Mucin-related tumor-associated carbohydrate antigens (TACAs) are important and interesting targets for cancer vaccine therapy. However, efficient access to a library of mucin-related TACAs remains a challenging task. One of the key issues is the challenging construction of α-GalNAc linkages. Here, we report highly stereoselective α-glycosylation with GalN-phenyl trifluoroacetimidate donors, which features excellent yields, outstanding stereoselectivities, broad substrate scope and mild reaction conditions. This method is successfully applied to highly stereoselective synthesis of GalN-α--Ser, which served as the common intermediate for collective synthesis of a wide range of TACAs including T antigen, ST antigen, 2,6 STF antigen, 2,3 STF antigen, glycophorin and cores 1-8 mucin-type -glycans. In particular, the rationale for this highly stereoselective α-glycosylation is provided for the first time using DFT calculations and mechanistic studies, highlighting the crucial roles of reagent combinations (TMSI and PhPO) and the H-bonding directing effect of the N group.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11062124 | PMC |
| http://dx.doi.org/10.1039/d4sc01348d | DOI Listing |
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