Synthesis and purity assessment of tetra- and pentaacyl lipid A of Chlamydia containing (R)-3-hydroxyicosanoic acid

Zamyatina, Alla; Sekljic, Harald; Brade, Helmut; Kosma, Paul

doi:10.1016/j.tet.2004.10.017

Cited by 17 publications

(15 citation statements)

References 45 publications

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“…The fatty acid moiety, 3‐( R )‐ p ‐methoxybenzyloxy‐palmitic acid (Fig. 1j), was prepared according to a method previously reported [14] by acylation of a 3‐hydroxy group to obtain a tri‐fatty acyl disaccharide (Fig. 1k).…”

Section: Methodsmentioning

confidence: 99%

Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis

Sawada

Ogawa

Asai

et al. 2007

Clinical and Experimental Immunology

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SummaryPorphyromonas gingivalis is a Gram-negative anaerobic oral black-pigmented bacterium closely associated with chronic periodontitis. Lipopolysaccharide (LPS) derived from P. gingivalis is shown to be unusual because the LPS contains a greater number of lipid A species, such as tri-, tetra-, and/or pentaacylated lipid As. In this study, a lipid A possessing penta-fatty acyl chains derived from P. gingivalis strain 381 (compound PG-381-5FA) was synthesized, and examined for its immunobiological activities, compared with a tri-acylated lipid A (compound PG-381-3FA) synthesized previously. Compound PG-381-5FA, similar to compound PG-381-3FA, demonstrated weaker activity in a Limulus test as compared with Escherichia coli-type synthetic lipid A (compound 506). Compound PG-381-5FA, followed by compound PG-381-3FA, induced KC, interleukin-6, and tumour necrosis factor-a production in peritoneal macrophages from LPS-responsive C3H/HeN mice, but not in those from LPS-hyporesponsive C3H/HeJ mice. Furthermore, compound PG-381-5FA, as well as compound PG-381-3FA, activated nuclear factor-kB via Toll-like receptor (TLR)4/mD-2, but not TLR2, in a manner similar to compound 506, and worked as an antagonist for compound 506-induced cell activation. In the case of human peripheral blood mononuclear cells, compound PG-381-5FA showed much stronger IL-6-inducing activity than compound PG-381-3FA. The present results demonstrate that the chemical synthesis of a penta-acylated lipid A, mimicking the natural lipid A portion of LPS from P. gingivalis, is attributable to immune cell activation through TLR4, similar to that of compound 506.

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Section: Methodsmentioning

confidence: 99%

Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis

Sawada

Ogawa

Asai

et al. 2007

Clinical and Experimental Immunology

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“…[41][42][43][44][47][48][49] The other strategy is to synthesize the lipidated monosaccharides first and then stitch them together by a glycosylation reaction, which can be challenging sometimes due to the increased steric hindrance of the glycosyl donors and acceptors. 37,40,45,[50][51][52][53][54] Both strategies will be discussed in great detail with individual examples presented below.…”

Section: Chemical Synthesis Of Lipid a And Its Derivativesmentioning

confidence: 99%

Progress in the synthesis and biological evaluation of lipid A and its derivatives

Gao

Guo

2017

Medicinal Research Reviews

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Lipid A is one of the core structures of bacterial lipopolysaccharides (LPSs), and it is mainly responsible for the strong immunostimulatory activities of LPS through interactions with the Toll-like receptors and other molecules in the human immune system. To obtain structurally homogeneous and well-defined lipid As and its derivatives in quantities meaningful for various biological studies and applications, their chemical synthesis has become a focal point. This review has provided a survey of significant progresses made in the synthesis of lipid A, and its derivatives that carry diverse saturated and unsaturated lipids, have the phosphate group at its reducing end replaced with a more stable phosphate or carboxyl group, or lack the reducing end phosphate or both phosphate groups, as well as progresses in the synthesis of LPS analogs and other lipid A conjugates. These synthetic molecules have facilitated the elucidation of the structure-activity relationships of lipid A useful for the design and development of lipid A based therapeutics, such as those utilized to treat sepsis, and other medical applications, for example the use of monophosphoryl lipid A as a carrier molecule for the study of fully synthetic self-adjuvanting conjugate vaccines. These topics are also briefly covered in the current review.

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“…Over the years, these and other classes of 2-NHTroc glycosyl donors have been used in glycoside and oligosaccharide synthesis: as trichloroacetimidates, 165,238,258,277, for the synthesis of pyruvated saccharide fragments, 280,304 Lipid A derivatives, 165,281,288,290,294,297,298,305,306 glycopeptides, 277,284,285 lactosaminyl donors, 282,307 Re-type lipopolysaccharides, 289 sialyl Lewis X glycolipids, 291,301 gangliosides, 292 peptidoglycan partial structures, 258,308 thiooligosaccharide analogues 286 of Nod factors, carbohydrate antigens, 295,302 sialyl-trimeric-Lewis X, 300 hyaluronan trisaccharides, 309 meonomycin A analogues, 310 and ceramidated GLA-60 293 derivatives; as fluorides, 282,311,312 for the synthesis of lactosaminyl donors, glycosylamines, 312 and tumor-associated antigen 311 Globo-H; as chlorides; 313 as thioglycosides, 283,286,[314][315][316][317][318][319][320][321][322]…”

Section: Alkoxycarbamoyl Derivatives 2-alkoxycarb-mentioning

confidence: 99%

“…314 Its sensitivity to alcoholysis under basic conditions permits convenient transformations into other carbamates. Removal of the Troc group to liberate the primary amine is typically accomplished by reductive elimination using Zn in AcOH, 259,270,271,277,280,282,283,285,[290][291][292] Zn-Cu alloy in AcOH, 258,288,289,297,298,308,335 Zn and acidic buffer, 293,336 Cd-Pb in AcOH, 309,331,337 or more recently, using (Bu 3 Sn) 2 338 in DMF. The use of Zn-N-methylimidazole, 339 in particular, allows selective deprotection of Troc in the presence of reducible and acid-sensitive functionalities.…”

Section: Alkoxycarbamoyl Derivatives 2-alkoxycarb-mentioning

confidence: 99%

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

Bongat

Demchenko

2007

Carbohydrate Research

200

110

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Synthesis and purity assessment of tetra- and pentaacyl lipid A of Chlamydia containing (R)-3-hydroxyicosanoic acid

Cited by 17 publications

References 45 publications

Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis

Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis

Progress in the synthesis and biological evaluation of lipid A and its derivatives

Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars

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