Synthetic approach to lipid A: Preparation of phosphorylated disaccharides containing (R)-3-hydroxyacyl and (R)-3-acyloxyacyl groups

Inage, Masaru; Chaki, Haruyuki; Imoto, Masahiro; Shimamoto, Takuya; Kusumoto, Shoichi; Shiba, Tetsuo

doi:10.1016/s0040-4039(00)81830-4

“…The 4,6‐dihydroxy sugar (Fig. 1C) was prepared from d ‐glucosamine hydrochloride (Aldrich) in five steps; protection of the 2‐amino group with 9‐fluorenylmethyl chloroformate (Fmoc‐Cl, Aldrich), allyl glycoside formation with HCl/dioxane/allyl alcohol, 4,6‐benzylidenation with benzaldehyde dimethyl acetal (Aldrich) and p ‐toluenesulfonic acid in N,N ‐dimethylformamide (DMF), benzylation of the 3‐hydroxy group with benzyl bromide (Aldrich) and Ag 2 O (Aldrich) in CH 2 Cl 2 [12], and then deprotection of the 4,6‐benzylidene group with HCl/dioxane.…”

Section: Methodsmentioning

confidence: 99%

Immunobiological activities of a chemically synthesized lipid A ofPorphyromonas gingivalis

Ogawa

¹

,

Asai

²

,

Yamamoto

³

et al. 2000

FEMS Immunology &Amp; Medical Microbiology

24

0

1

View full text Add to dashboard Cite

A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381), which is similar to its natural lipid A, demonstrated no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). On the other hand, compound PG-381 had stronger hemagglutinating activities on rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B resulted in the inhibition of mitogenic activities, however, compound 506 did not show these capacities. Additionally, compound PG-381 showed a lower level of activity in inducing cytokine production in peritoneal macrophages and gingival fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound 506. Thus, this study demonstrates that the chemical synthesis of lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low endotoxic potency and immunobiological activity.

show abstract

“…The 4,6-dihydroxy sugar (Fig. 1C) was prepared from D-glucosamine hydrochloride (Aldrich) in ¢ve steps; protection of the 2-amino group with 9-£uorenylmethyl chloroformate (Fmoc-Cl, Aldrich), allyl glycoside formation with HCl/dioxane/allyl alcohol, 4,6-benzylidenation with benzaldehyde dimethyl acetal (Aldrich) and p-toluenesulfonic acid in N,N-dimethylformamide (DMF), benzylation of the 3-hydroxy group with benzyl bromide (Aldrich) and Ag 2 O (Aldrich) in CH 2 Cl 2 [12], and then deprotection of the 4,6-benzylidene group with HCl/dioxane.…”

Section: Preparation and Puri¢cation Of Lipid Amentioning

confidence: 99%

Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalis

Ogawa

¹

2000

FEMS Immunology and Medical Microbiology

View full text Add to dashboard Cite

A synthetic lipid A of Porphyromonas gingivalis strain 381 (compound PG-381), which is similar to its natural lipid A, demonstrated no or very low endotoxic activities as compared to Escherichia coli-type synthetic lipid A (compound 506). On the other hand, compound PG-381 had stronger hemagglutinating activities on rabbit erythrocytes than compound 506. Compound PG-381 also induced mitogenic responses in spleen cells from lipopolysaccharide (LPS)-hyporesponsive C3H/HeJ mice, as well as LPS-responsive C3H/HeN mice. The addition of polymyxin B resulted in the inhibition of mitogenic activities, however, compound 506 did not show these capacities. Additionally, compound PG-381 showed a lower level of activity in inducing cytokine production in peritoneal macrophages and gingival fibroblasts from C3H/HeN mice, but not C3H/HeJ mice, in comparison to compound 506. Thus, this study demonstrates that the chemical synthesis of lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, confirms its low endotoxic potency and immunobiological activity.

show abstract

“…Compounds 403 to 405 were all synthesized from a common disaccharide intermediate, i.e., allyl 2-acylamino-6-O-(3-0-acyl-2-acylamino-2-deoxy-p-D-glucopyranosyl)-4-0benzyl-2-deoxy-,3-D-glucopyranoside, in which the acyl moiety was an (R)-3-benzyl-oxytetradecanoyl group. This intermediate was obtained by coupling a peracetyl oxazoline derivative with allyl 2-acetamido-3-O-benzoyl-4-O-benzyl-2deoxy-p-D-glucopyranoside and then introducing 3-benzyloxyacyl moieties stepwise, according to the principle described previously (4). Removal of protecting groups afforded the dephospho derivative 403, whereas their removal after introduction of phosphate moieties gave 404, 405, and 406.…”

mentioning

confidence: 99%

Immunobiologically active lipid A analogs synthesized according to a revised structural model of natural lipid A

Kotani

¹

,

Takada²,

Tsujimoto

³

et al. 1984

View full text Add to dashboard Cite

Synthetic lipid A analogs which have two amide-bound and two ester-bound (R)-3-hydroxytetradecanoyl groups at the C-2 and-2' and C-3 and-3' positions of O(1-6)glucosamine disaccharide monoor diphosphates showed high activities in most in vitro assays, and the lethality of a diphosphate derivative to galactosaminetreated mice was almost comparable to that of natural lipid A. The pyrogenicity and Shwartzman induction activity of the synthetic analogs, however, were much less than those of natural lipid A.

show abstract

Synthetic approach to lipid A: Preparation of phosphorylated disaccharides containing (R)-3-hydroxyacyl and (R)-3-acyloxyacyl groups

Cited by 28 publications

References 6 publications

Immunobiological activities of a chemically synthesized lipid A ofPorphyromonas gingivalis

Immunobiological activities of a chemically synthesized lipid A ofPorphyromonas gingivalis

Immunobiological activities of a chemically synthesized lipid A of Porphyromonas gingivalis

Immunobiologically active lipid A analogs synthesized according to a revised structural model of natural lipid A

Contact Info

Product

Resources

About