Synthesis and biological activities of pyrancarboxylic acid derivatives toward LPS-antagonists as antisepticemia drugs

摘要

LPS-antagonists are promising candidates for anti-septicemia drugs. The lipid A molecule, the core component of LPS for its endotoxic activity, was used as a lead compound to search for stable compounds having LPS-antagonistic activity. From our investigation of lipid A-type pyrancarboxylic acid derivatives, the following were revealed:1) the 1-alpha-phosphate group of the lipid A molecule was exchangeable to an alpha-oriented carboxy group without loss of activity; 2) the number of fatty acid chains in the molecule is critical for whether it shows LPS-agonistic or-antagonistic activity; and 3) conversion of the ester bonds to ether bonds in lipid A-type LPS-antagonists did not affect their LPS-antagonistic activity. We also found several LPS-antagonistic pyrancarboxylic acid derivatives composed of monosaccharides.