Synthesis of Kdo-α-glycosides of lipid A derivatives

Rembold, Hansjör; Schmidt, Richard R.

doi:10.1016/0008-6215(93)84029-6

Cited by 17 publications

(9 citation statements)

References 53 publications

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“…One strategy is to assemble the disaccharide backbone first and finally introduce individual lipid chains at proper positions. [23–29] In this case, various positions of the disaccharide unit have to be differentially protected by orthogonal protecting groups, especially when different lipid chains present in the synthetic target. The second strategy is to build the lipidated monosaccharides first and then couple them together via a glycosylation reaction,[30–37] in which case the glycosylation reaction can be challenging, because of increased steric hindrance.…”

Section: Resultsmentioning

confidence: 99%

“…Although several syntheses of lipid A and MPLA have already been reported,[23–37] the uniqueness of 1 is that it contains a alkyne functionality, enabling its coupling with other molecules by click chemistry. In the meanwhile, an alkyne functionality can be readily transformed into a carboxyl or carbonyl group to facilitate other conjugation methods, such as that based on carboxylic acid-amine condensation reactions or based on reductive amination reactions.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor‐Associated Carbohydrate Antigen

Tang

Wang

Guo

2010

Chemistry A European J

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Monophosphoryl lipid A is a safe and potent immunostimulant and vaccine adjuvant, which is potentially useful for the development of effective carbohydrate-based conjugate vaccines. This paper presented a convergent and efficient synthesis of a monophosphoryl derivative of E. coli lipid A having an alkyne functionality at the reducing end, which is suitable for the coupling with various molecules. The coupling of this derivative to an N-modified analog of tumor-associated antigen GM3 by click chemistry is also presented.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor‐Associated Carbohydrate Antigen

Tang

Wang

Guo

2010

Chemistry A European J

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“…In this case, orthogonal protection of various disaccharide positions was a prerequisite, especially when lipid chains in the synthetic target had an asymmetrical distribution. [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%

“…One is to construct a versatile disaccharide and then install individual lipid chains at the specific positions. In this case, orthogonal protection of various disaccharide positions was a prerequisite, especially when lipid chains in the synthetic target had an asymmetrical distribution . 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 .…”

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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“…16 SAR studies showed that modification of the reducing end of the MPLA had little influence on its immunological activity. 10 The syntheses of lipid A and MPLA have been reported [17][18][19][20][21][22][23] (incomplete), but 3 is designed to have a functionality that will facilitate its coupling to other structures. For example, the azido group of 3 will enable the coupling of 3 to other molecules by click chemistry.…”

mentioning

confidence: 99%

Synthesis of a monophosphoryl lipid A derivative and its conjugation to a modified form of a tumor-associated carbohydrate antigen GM3

2009

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An efficient synthesis of a derivative of monophosphoryl lipid A suitable for coupling to various structures for the construction of glycoconjugate vaccines, and its conjugation with an N-modified form of the tumor-associated antigen GM3, is presented.Lipid A (1) is the hydrophobic domain of lipopolysaccharides (LPS) of the outer membranes of Gram-negative bacteria. 1 Its structure consists of a β-1,6-linked di-glucosamine with 1,4′-di-O-phosphorylation and 2,2′-N-and 3,3′-O-acylation (Figure 1). Lipid A of different bacterial origins can vary significantly in terms of the number and structure of the fatty acids.

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Synthesis of Kdo-α-glycosides of lipid A derivatives

Cited by 17 publications

References 53 publications

Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor‐Associated Carbohydrate Antigen

Synthesis of a Monophosphoryl Derivative of Escherichia coli Lipid A and Its Efficient Coupling to a Tumor‐Associated Carbohydrate Antigen

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

Synthesis of a monophosphoryl lipid A derivative and its conjugation to a modified form of a tumor-associated carbohydrate antigen GM3

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