Synthesis and biological evaluation of Rhizobium sin-1 lipid A derivatives.

摘要: A highly convergent strategy for the synthesis of several derivatives lipid Rhizobium sin-1 has been developed. The approach employed advanced intermediate 3-O-acetyl-6-O-(3-O-acetyl-4,6-O-benzylidene-2-deoxy-2-phthalimido-beta-d-glucopyrano-syl)-2-azido-4-O-benzyl-2-deoxy-1-thio-alpha-d-glucopyranoside (5), which is protected in such a way that anomeric center, C-2 and C-2' amino groups, C-3 C-3' hydroxyls can be selectively functionalized. synthetic was used preparation 2-deoxy-6-O-[2-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d-glucopyranosyl]-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-alpha-d-glucopyranose (11) 2-deoxy-6-O-[2-deoxy-3-O-[(R)-3-hydroxy-hexadecanoyl]-2-[(R)-3-octacosanoyloxy-hexadecan]amido-beta-d-glucopyranosyl]-2-[(R)-3-hydroxy-hexadecan]amido-3-O-[(R)-3-hydroxy-hexadecanoyl]-d-glucono-1,5-lactone (13), contain an unusual octacosanoic acid moiety differ oxidation state center. results biological studies indicate 11 13 lack proinflammatory effects Escherichia coli lipopolysaccharides (LPS). Furthermore, emulated ability heterogeneous R. LPS to antagonize enteric LPS, providing evidence critical role gluconolactone mediating this antagonistic effect. Compound first example derivative devoid phosphate but possesses properties, making it attractive lead compound development drug use treatment Gram-negative septicemia.