Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Efficient Divergent Synthesis of New Immunostimulant 4?-Modified ?-Galactosylceramide Analogues.

ABSTRACT: A synthesis strategy for the swift generation of 4?-modified ?-galactosylceramide (?-GalCer) analogues is described, establishing a chemical platform to comprehensively investigate the structure-activity relationships (SAR) of this understudied glycolipid part. The strategy relies on a late-stage reductive ring-opening of a p-methoxybenzylidene (PMP) acetal to regioselectively liberate the 4?-OH position. The expediency of this methodology is demonstrated by the synthesis of a small yet diverse set of analogues, which were tested for their ability to stimulate invariant natural killer T-cells (iNKT) in vitro and in vivo. The introduction of a p-chlorobenzyl ether yielded an analogue with promising immunostimulating properties, paving the way for further SAR studies.

SUBMITTER: Janssens J

PROVIDER: S-EPMC5467197 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Efficient Divergent Synthesis of New Immunostimulant 4″-Modified α-Galactosylceramide Analogues.

Janssens Jonas J Decruy Tine T Venken Koen K Seki Toshiyuki T Krols Simon S Van der Eycken Johan J Tsuji Moriya M Elewaut Dirk D Van Calenbergh Serge S

ACS medicinal chemistry letters 20170505 6

A synthesis strategy for the swift generation of 4″-modified α-galactosylceramide (α-GalCer) analogues is described, establishing a chemical platform to comprehensively investigate the structure-activity relationships (SAR) of this understudied glycolipid part. The strategy relies on a late-stage reductive ring-opening of a <i>p</i>-methoxybenzylidene (PMP) acetal to regioselectively liberate the 4″-OH position. The expediency of this methodology is demonstrated by the synthesis of a small yet d ...[more]

PMID: 28626526

Similar Datasets

Efficient, divergent synthesis of cryptophycin unit A analogues.

Project description:A flexible and divergent synthesis of cryptophycin unit A analogues is described. This method relies on iridium-catalysed stereo- and enantioselective crotylation and chemoselective one-pot oxidative olefination to access common intermediate . Heck, cross metathesis, and Suzuki-Miyaura reactions are illustrated for the generation of methyl ester unit A analogues .

| S-EPMC3494784 | biostudies-literature

Divergent synthetic approach to 6''-modified ?-GalCer analogues.

Project description:A synthetic approach is presented for the synthesis of galacturonic acid and D-fucosyl modified KRN7000. The approach allows for late-stage functionalisation of both the sugar 6''-OH and the sphingosine amino groups, which enables convenient synthesis of promising 6''-modified KRN7000 analogues.

| S-EPMC3246390 | biostudies-literature

Synthesis and Immunological Activity of Novel Oligo(ethylene glycol) Analogues of α-Galactosylceramide.

Project description:CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production. When immunized with quadrivalent split influenza virus in BALB/c mice, the novel ceramide analogues with a longer oligo (ethylene glycol) chain length induced significant levels of antibody (IgG) with Th1-polarized immune response.

| S-EPMC9245117 | biostudies-literature

Synthesis and evaluation of new endomorphin analogues modified at the Pro(2) residue.

Project description:Six new endomorphin analogues, incorporating constrained amino acids in place of native proline have been synthesized. Residues of (S)-azetidine-2-carboxylic acid (Aze), 3,4-dehydro-(S)-proline (Delta(3)Pro), azetidine-3-carboxylic acid (3Aze) and dehydro-alanine (DeltaAla) have been used to prepare [Delta(3)Pro(2)]EM-2 (1), [Aze(2)]EM-1 (2), [Aze(2)]EM-2 (3), [3Aze(2)]EM-1 (4), [3Aze(2)]EM-2 (5) and [DeltaAla(2)]EM-2 (6). Binding assays and functional bioactivities for mu- and delta-receptors are reported. The highest affinity, bioactivity and selectivity are shown by peptides 2 and 3 containing the Aze residue.

| S-EPMC2737817 | biostudies-literature

A New and Efficient Approach to the Synthesis of Nicotine and Anabasine Analogues.

Project description:A straightforward and practical approach was established for the synthesis of nicotine and anabasine analogues by the cyclization of mesylated 1-(3-pyridinyl)-1,4, and 1,5-diol derivatives to form the pyrrolidino or piperidino fragments. Nicotine analogue (S)-15 was prepared with good enantioselectivity using the developed azacyclization procedure of nonracemic (R)-1-pyridin-3-yl-butane-1,4-diol, which was obtained by the borane-mediated reduction of ketone 12 in the presence of the spiroborate ester derived from diphenyl prolinol and ethylene glycol.

| S-EPMC2811585 | biostudies-literature

Synthesis and evaluation of amino-modified alpha-GalCer analogues.

Project description:Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3- and 4-positions of suitable phytosphingosine-derived precursors. The influence of these modifications on the interaction with the T-cell receptor of NKT cells was investigated, as well as the capacity of the amino-modified analogues to induce a cytokine response after in vivo administration.

| S-EPMC2903208 | biostudies-literature

Total synthesis of Septocylindrin B and C-terminus modified analogues.

Project description:The total synthesis is reported of the peptaibol Septocylindrin B which is related to the well documented channel forming peptaibol antibiotic Alamethicin. Several analogues were synthesized with a modified C-terminus, to investigate the SAR of the terminal residue Phaol. All these peptides were tested for their membrane perturbation properties by fluorescent dye leakage assay and for their antibacterial activity.

| S-EPMC3527430 | biostudies-literature

Synthesis and antileukemic activities of C1-C10-modified parthenolide analogues.

Project description:Parthenolide (PTL) is a sesquiterpene lactone natural product with anti-proliferative activity to cancer cells. Selective eradication of leukemic stem cells (LSCs) over healthy hematopoietic stem cells (HSCs) by PTL has been demonstrated in previous studies, which suggests PTL and related molecules may be useful for targeting LSCs. Eradication of LSCs is required for curative therapy. Chemical optimizations of PTL to improve potency and pharmacokinetic parameters have focused largely on the α-methylene-γ-butyrolactone, which is essential for activity. Conversely, we evaluated modifications to the C1-C10 olefin and benchmarked new inhibitors to PTL with respect to inhibitory potency across a panel of cancer cell lines, ability to target drug-resistant acute myeloid leukemia (AML) cells, efficacy for inhibiting clonal growth of AML cells, toxicity to healthy bone marrow cells, and efficiency for promoting intracellular reactive oxygen species (ROS) levels. Cyclopropane 4 was found to possess less toxicity to healthy bone marrow cells, enhanced potency for the induction of cellular ROS, and similar broad-spectrum anti-proliferative activity to cancer cells in comparison to PTL.

| S-EPMC4697833 | biostudies-literature

Efficient synthesis of 4-substituted-<i>ortho</i>-phthalaldehyde analogues: toward the emergence of new building blocks.

Project description:4-Methoxy-ortho-phthalaldehyde and 4-hydroxy-ortho-phthalaldehyde are potentially useful molecules for fluorimetric analysis of a variety of amines and for the elaboration of complex molecular architectures. Nevertheless, literature generally describes their synthesis in very low yield (below 5%), mainly due to the inefficiency of the last oxidation step. In this paper, we report a reliable synthesis of 4-substituted-ortho-phthalaldehyde analogues in 51% overall yield owing to the addition of a protecting step of the unstable key intermediate 4,5-dihydroisobenzofuran-5-ol. Oxidation and deprotection steps were also studied in order to provide an effective availability of these two dialdehyde compounds that may increase their future applications.

| S-EPMC6444388 | biostudies-literature

Synthesis of C-glycoside analogues of ?-galactosylceramide via linear allylic C-H oxidation and allyl cyanate to isocyanate rearrangement.

Project description:C-Glycoside analogues of ?-galactosylceramide were synthesized in which several significant modifications known to promote Th-1 cytokine production were included. The key transformations include C-H oxidation, Sharpless asymmetric epoxidation, olefin cross metathesis, and an allyl cyanate to isocyanate rearrangement.

| S-EPMC3263403 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data