Chemical Synthesis of d-glycero-d-manno-Heptose 1,7-Bisphosphate and Evaluation of Its Ability to Modulate NF-κB Activation

Org Lett. 2017 Jun 16;19(12):3079-3082. doi: 10.1021/acs.orglett.7b01158. Epub 2017 May 25.

Abstract

d-glycero-d-manno-Heptose 1,7-bisphosphate (HBP) is the precursor for heptose residues found in Gram-negative bacterial membrane surface glycoproteins and glycolipids. HBP β-anomer was recently reported to be a pathogen-associated molecular pattern (PAMP) that regulates TIFA-dependent immunity. Herein, we report the chemical synthesis of HBP α- and β-anomers, which highlights a C-7 carbon homologation via the Corey-Chaykovsky reaction, and the introduction of a phosphate group at the anomeric position using the Mitsunobu reaction. Furthermore, NF-κB reporter assaying revealed that HBP β-anomer activates the NF-κB signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't