Convergent Synthesis of Sialyl LewisX-O-Core-1 Threonine
- 11 April 2018
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 83 (9) , 4963-4972
Abstract
Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl LewisX (sLeX) linked to a Core-1-O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using α-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.Keywords
Funding Information
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK107405)
- National Heart, Lung, and Blood Institute (R01HL128237)
- National Institute of General Medical Sciences (P41GM103694, U01GM116196)
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