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]-α- and β-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-(tetradecanoyloxy)tetradecanoyl]-α-d-glucopyranoside (44) and carboxymethyl 2-deoxy-2-[(R)-3-(hydroxy)tetradecanamido]-4-O-phosphono-3-O-[(R)-3-(tetradecanoyloxy)tetradecanoyl]-α-d-glucopyranoside (48). Of these compounds, 32 was most pronounced in terms of LPS-antagonistic activity.