87357-65-1

Upstream product

• 28715-21-1 (R)-3-hydroxytetradecanoic acid 
• 70-11-1 α-bromoacetophenone 
• 151763-75-6 (R)-3-hydroxytetradecanoic acid ethyl ester 
• 620-72-4 phenyl 2-bromoacetate 
• 143-07-7 lauric acid 
• 76062-97-0 methyl (R)-3-hydroxytetradecanoate 
• 22348-97-6 methyl 3-oxotetradecanoate 

Downstream Products

• 112475-18-0 (3R)-3-(benzyloxymethoxy)tetradecanoic acid phenacyl ester 
• 87357-66-2 phrnacyl (R)-3-(benzyloxy)tetradecanoate 
• 112475-20-4 (3R)-3-tetradecanoyloxytetradecanoic acid phenacyl ester 
• 91681-56-0 (3R)-3-dodecanoyloxytetradecanoic acid 
• 339316-63-1 (R)-3-Dodecanoyloxy-tetradecanoic acid 2-oxo-2-phenyl-ethyl ester 
• 88862-41-3 C₇₁H₁₀₆N₂O₁₅ 
• 87357-75-3 (R)-3-Benzyloxy-tetradecanoic acid (2R,3S,4R,5R,6R)-5-acetylamino-2-((2R,3R,4R,5S,6R)-3-acetylamino-4-benzyloxy-5-hydroxy-6-hydroxymethyl-tetrahydro-pyran-2-yloxymethyl)-6-allyloxy-4-((R)-3-benzyloxy-tetradecanoyloxy)-tetrahydro-pyran-3-yl ester 

Relevant academic research and scientific papers

SYNTHETIC GLUCOPYRANOSYL LIPID ADJUVANTS

PROBLEM TO BE SOLVED: To provide a novel glucopyranosyl lipid adjuvant (GLA) for inducing or enhancing immune responses, and a vaccine composition and a pharmaceutical composition comprising the GLA. SOLUTION: The present invention provides a GLA represented by a compound of the following formula, and a vaccine composition and a pharmaceutical composition comprising the GLA. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPOandINPIT

Chemical synthesis of burkholderia lipid a modified with glycosyl phosphodiester-linked 4-amino-4-deoxy-β-L-arabinose and its immunomodulatory potential

Modification of the Lipid A phosphates by positively charged appendages is a part of the survival strategy of numerous opportunistic Gram-negative bacteria. The phosphate groups of the cystic fibrosis adapted Burkholderia Lipid A are abundantly esterified by 4-amino-4-deoxy-b-larabinose (β-L-Ara4N), which imposes resistance to antibiotic treatment and contributes to bacterial virulence. To establish structural features accounting for the unique pro-inflammatory activity of Burkholderia LPS we have synthesised Lipid A substituted by β-L-Ara4N at the anomeric phosphate and its Ara4N-free counterpart. The double glycosyl phosphodiester was assembled by triazolyl-tris-(pyrrolidinyl)phosphonium-assisted coupling of the β-L-Ara4N H-phosphonate to α-lactol of β(1→6) diglucosamine, pentaacylated with (R)-(3)-acyloxyacyl-and Alloc-protected (R)-(3)-hydroxyacyl residues. The intermediate 1,1'-glycosyl-H-phosphonate diester was oxidised in anhydrous conditions to provide, after total deprotection, β-L-Ara4N-substituted Burkholderia Lipid A. The β-L-Ara4N modification significantly enhanced the pro-inflammatory innate immune signaling of otherwise non-endotoxic Burkholderia Lipid A.

SYNTHETIC DERIVATIVES OF MPL AND USES THEREOF

In one aspect, the present disclosure provides compounds of formulae (I) and (II). In another aspect, a compound of formula (I) or (II) is formulated into compositions with an antigen, optionally with a vesicle. In some embodiments, compositions are administered intramuscularly.

Divergent synthesis and biological activities of lipid A analogues of shorter acyl chains

Novel lipid A analogues which possess four (R)-3-hydroxyacyl moieties of shorter chain length were synthesized via new divergent synthetic route in order to clarify the effect of the chain length of acyl groups to the biological activity: a disaccharide 4

Chemical Synthesis of a Biosynthetic Precursor of Lipid A with a Phosphorylated Tetraacyl Disaccharide Structure

2,2'-N:3,3'-O-Tetrakis-β(1-6)-D-glucosamine disaccharide 1,4'-bis(phosphate) and its dephospho derivatives were synthesized.The bisphosphate prepared was shown to be identical with a natural biosynthetic precursor of lipid A which corresponds to the lipophilic part of lipopolysaccharide (LPS) in bacterial cell wall.The synthetic bis- and monophosphates exhibited many of typical endotoxic activities of LPS.Consequently, this work established the chemical structure of the biosynthetic precursor of lipid A and elucidated the fundamental structure required for the expression of these activities.

SYNTHESIS OF THE OPTICALLY ACTIVE 4-O-PHOSPHONO-D-GLUCOSAMINE DERIVATIVES RELATED TO THE NONREDUCING-SUGAR SUBUNIT OF BACTERIAL LIPID A

The optically active lipid A-subunit homologs named GLA-46, GLA-47, GLA-59, and GLA-60 have been synthesized stepwise by successive acylation at N-2 and O-3 of benzyl 2-amino-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside with the 3-O-(benzyloxy)methyl

SYNTHETIC APPROACH TO LIPID A: PREPARATION OF PHOSPHORYLATED DISACCHARIDES CONTAINING (R)-3-HYDROXYACYL GROUPS

A synthetic route was established to construct the proposed structure of lipid A which consists of β(1-6) glucosamine disaccharide 1,4'-diphosphate O,N-acylated with (R)-3-hydroxy- or (R)-3-acyloxytetraadecanoic acid.