Syntheses of 1-O-carboxyalkyl GLA-60 analogues.
As part of our ongoing study to survey potent LPS antagonists, the following six compounds were synthesized in an efficient manner: 3-carboxypropyl and carboxymethyl 2-deoxy-2-(2,2-difluorotetradecanamido)-4-O-phosphono-3-O-[(R)-3- (tetradecanoyloxy)tetradecanoyl]-alpha- and beta-D-glucopyranosides (11 and 23; 32 and 36), as well as the non-fluorinated equivalents, carboxymethyl 2-deoxy-4-O-phosphono-2-tetradecanamido-3-O-[(R)-3-(tetradecano yloxy)- tetradecanoyl]-alpha-D-glucopyranoside (44) and carboxymethyl 2-deoxy-2-[(R)-3-(hydroxy)tetradecanamido]-4-O-phosphono-3-O-[(R)- 3- (tetradecanoyloxy)tetradecanoyl]-alpha-D-glucopyranoside (48). Of these compounds, 32 was most pronounced in terms of LPS-antagonistic activity.
Shiozaki
M
M
Exploratory Chemistry Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan.
Deguchi
N
N
Macindoe
W M
WM
Arai
M
M
Miyazaki
H
H
Mochizuki
T
T
Tatsuta
T
T
Ogawa
J
J
Maeda
H
H
Kurakata
S
S
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D004926:Escherichia coli / Q000737:chemistry; D005960:Glucosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006017:Glycolipids / Q000494:pharmacology; D008050:Lipid A / Q000031:analogs & derivatives / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011239:Prednisolone / Q000494:pharmacology; D012475:Salmonella / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005960:Glucosides; D006017:Glycolipids; D008050:Lipid A; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C040142:lipid A precursors, bacterial; C044283:lipid X; D011239:Prednisolone