103426-88-6Relevant articles and documents
Synthesis of monophosphoryl lipid A using 2-naphtylmethyl ethers as permanent protecting groups
Verpalen, Enrico C.J.M.,Brouwer, Arwin J.,Boons, Geert-Jan
, (2020)
Lipid A, which is a conserved component of lipopolysaccharides of gram-negative bacteria, has attracted considerable interest for the development of immuno-adjuvants. Most approaches for lipid A synthesis rely on the use of benzyl ethers as permanent protecting groups. Due to the amphiphilic character of lipid A, these compounds aggregate during the hydrogenation step to remove benzyl ethers, resulting in a sluggish reaction and by-product formation. To address this problem, we have developed a synthetic approach based on the use of 2-naphtylmethyl ether (Nap) ethers as permanent protecting group for hydroxyls. At the end of a synthetic sequence, multiple of these protecting groups can readily be removed by oxidation with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). Di-allyl N,N-diisopropylphosphoramidite was employed to install the phosphate ester and the resulting allyl esters were cleaved using palladium tetrakistriphenylphosphine. The synthetic strategy allows late stage introduction of different fatty acids at the amines of the target compound, which is facilitated by Troc and Fmoc as orthogonal amino-protecting groups.
Intermediate, synthesis and application of vaccine adjuvant MPLA
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Paragraph 0309-0311, (2021/10/27)
The invention discloses an intermediate of a vaccine adjuvant MPLA, and synthesis and application thereof. The intermediate provided by the invention uses Nap as a protecting group, and can be conveniently removed in subsequent operation. The synthesis route is short, and the total yield is obviously increased. For synthesis and amplification MPLA, a foundation is provided.
Intermediate, synthesis and application of vaccine adjuvant MPLA
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Paragraph 0438-0440, (2021/10/27)
The invention discloses an intermediate of a vaccine adjuvant MPLA, and synthesis and application thereof. The intermediate provided by the invention takes the allyl phosphate ligand as MPLA phosphate group source, Nap is a protecting group, and can be conveniently removed in subsequent operation. The synthesized intermediate route is short, and the total yield is obviously increased. For synthesis and amplification MPLA, a foundation is provided.
Intermediate, synthesis and application of vaccine adjuvant MPLA
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Paragraph 0291-0293, (2021/10/27)
The invention discloses an intermediate of a vaccine adjuvant MPLA, and synthesis and application thereof. The intermediate provided by the invention takes the allyl phosphate ligand as MPLA phosphate group source, Nap is a protecting group, and can be conveniently removed in subsequent operation. The synthesized intermediate route is short, and the total yield is obviously increased. For synthesis and amplification MPLA, a foundation is provided.
Intermediate, synthesis and application of vaccine adjuvant MPLA
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Paragraph 0271-0273, (2021/10/27)
The invention discloses an intermediate of a vaccine adjuvant MPLA, and synthesis and application thereof. The intermediate provided by the invention takes the allyl phosphate ligand as MPLA phosphate group source, Nap is a protecting group, and can be conveniently removed in subsequent operation. The synthesized intermediate route is short, and the total yield is obviously increased. For synthesis and amplification MPLA, a foundation is provided.
Intermediate, synthesis and application of vaccine adjuvant MPLA
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Paragraph 0271-0173, (2021/10/27)
The invention discloses an intermediate of a vaccine adjuvant MPLA, and synthesis and application thereof. The intermediate provided by the invention takes the allyl phosphate ligand as MPLA phosphate group source, Nap is a protecting group, and can be conveniently removed in subsequent operation. The synthesized intermediate route is short, and the total yield is obviously increased. For synthesis and amplification MPLA, a foundation is provided.
A divergent synthesis of lipid A and its chemically stable unnatural analogues
Liu, Wen-Chi,Oikawa, Masato,Fukase, Koichi,Suda, Yasuo,Kusumoto, Shoichi
, p. 1377 - 1385 (2007/10/03)
Lipid A and its two chemically stable analogues, wherein the glycosidic phosphoryl groups in lipid A is replaced with 2-(phosphonooxy)ethyl or carboxymethyl groups, have been synthesized by an improved and divergent route via a common allyl glycoside intermediate in which the 4-hydroxy group was protected as a benzyl ether. The total yields were more than 20% for 11 or 12 steps starting from allyl 4,6-O-benzylidene-2-deoxy-2- (trichloroethoxycarbonylamino)-D-glucopyranoside. These synthetic chemically stable analogues induce interleukin-6 and tumor necrosis factor a in human peripheral whole blood cells with potencies comparable to those by natural- type synthetic lipid A. The Limulus activities of both analogues were found to be even stronger than the activity of the natural-type one.
Total Synthesis of Escherichia coli Lipid A, the Endotoxically Active Principle of Cell-Surface Lipopolysaccharide
Imoto, Masahiro,Yoshimura, Hiroyuki,Shimamoto, Tetsuo,Sakaguchi, Nobuki,Kusumoto, Shoichi,Shiba, Tetsuo
, p. 2205 - 2214 (2007/10/02)
Chemical synthesis are described of polyacylated β(1->6) glucosamine disaccharide 1,4'-bis(phosphate), which corresponds to the proposed structure of E. coli lipid A, and of its dephospho derivatives.The synthetic bisphosphate proved to be identical with
Chemical synthesis of 1-dephospho derivative of escherichia coli lipid A
Kusumoto,Yoshimura,Imoto,Shimamoto,Shiba
, p. 909 - 912 (2007/10/02)
1-Dephospho E. coli lipid A (3) was synthesized and shown to be identical with the corresponding derivative isolated from bacterial cells. This provides the unequivocal evidence supporting the structure of E. coli lipid A (2) recently proposed by us.
