160280-67-1

Upstream product

• 596-43-0 bromo-triphenyl-methane 
• 202812-10-0 (2S,3S,4S)-2-azido-3,4-di-O-benzyl-octadecan-1,3,4-triol 
• 4099-88-1 (3aS,6R,6aS)-6-(hydroxymethyl)-2,2-dimethyl-tetrahydrofuro[3,4-d]-[1,3]dioxol-4-ol 
• 77844-50-9 (2S,3S,4R)-2-aminooctadecane-1,3,4-triol hydrochloride 
• 160280-65-9 (2R,3R,4R)-1,3,4-trihydroxyoctadecan-2-yl methanesulfonate 
• 76-83-5 trityl chloride 
• 600168-67-0 2-azido-3,4-O-isopropylidene-1-O-triphenylmethyl-D-arabino-octadecane-1,3,4-triol 
• 600168-66-9 3,4-O-isopropylidene-1-O-triphenylmethyl-D-arabino-octadecane-1,2,3,4-tetraol 
• 160280-62-6 3,4-O-isopropylidene-1-O-triphenylmethyl-D-arabino-octadec-5-en-1,2,3,4-tetraol 
• 117168-59-9 (2S,3S,4R)-2-azido-1,3,4-octadecanetriol 
• 554-62-1 D-ribo-phytosphingosine 
• 100-44-7 benzyl chloride 
• 160280-66-0 (2S,3S,4R)-2-azido-1-(trityloxy)octadecane-3,4-diol 
• 100-39-0 benzyl bromide 

Downstream Products

• 160280-68-2 (1S,2S,3R)-2,3-Bis-benzyloxy-1-trityloxymethyl-heptadecylamine 
• 202812-10-0 (2S,3S,4S)-2-azido-3,4-di-O-benzyl-octadecan-1,3,4-triol 
• 676999-83-0 (2S,3S,4R)-2-azido-3,4-di-O-benzyl-1-O-(2-O-methyl-3,4,6-tri-O-benzyl-α-D-galactopyranosyl)-1,3,4-octadecanetriol 
• 1054682-27-7 (2S,3S,4R)-2-azido-3,4-di-O-benzyl-1-O-(3,4,6-tri-O-benzyl-2-deoxy-2-fluoro-α-D-galactopyranosyl)-1,3,4-octadecanetriol 
• 848827-63-4 Acetic acid (2S,3S,4R,5R,6S)-4,5-diacetoxy-2-((2S,3S,4R)-2-azido-3,4-bis-benzyloxy-octadecyloxy)-6-methyl-tetrahydro-pyran-3-yl ester 
• 848827-40-7 (2R,3S,4R,5R,6S)-2-((2S,3S,4R)-2-Azido-3,4-bis-benzyloxy-octadecyloxy)-3,4,5-tris-benzyloxy-6-methyl-tetrahydro-pyran 
• 676999-84-1 (2S,3S,4R)-2-amino-3,4-di-O-benzyl-1-O-(2-O-methyl-3,4,6-tri-O-benzyl-α-D-galactopyranosyl)-1,3,4-octadecanetriol 
• 676999-85-2 (2S,3S,4R)-2-docosanoylamino-3,4-di-O-benzyl-1-O-(2-O-methyl-3,4,6-tri-O-benzyl-α-D-galactopyranosyl)-1,3,4-octadecanetriol 
• 160280-70-6 (2S,3S,4R)-2-hexacosylamino-3,4-di-O-benzyl-1,3,4-octadecanetriol 
• 202812-11-1 3,4 di-O-benzylphytosphingosine 
• 160280-69-3 (2S,3S,4R)-3,4-di-O-benzyl-N-hexacosanoyl-1-O-trityl-2-amino-3,4-octadecanetriol 
• 951767-71-8 2-azido-3,4-di-O-benzyl-1-O-(2,3-di-O-benzyloxyl-4,6-O-benzyllidene-α-D-galactopyranosyl)-D-ribooctadecane-1,3,4-triol 
• 1201598-11-9 C₅₉H₇₇N₃O₈ 
• 1309198-89-7 C₆₆H₈₁N₃O₉ 

Relevant academic research and scientific papers

Synthesis and Evaluation of Acyl-Chain- and Galactose-6′′-Modified Analogues of α-GalCer for NKT Cell Activation

α-GalCer is an immunostimulating glycolipid that binds to CD1d molecules and activates invariant natural killer T (iNKT) cells. Here we report a scaled-up synthesis of α-GalCer analogues with modifications in the acyl side chain and/or at the galactose 6′′-position, together with their evaluation in vitro and in vivo. Analogues containing 11-phenylundecanoyl acyl side chains with aromatic substitutions (14, 16-21) and Gal-6′′-phenylacetamide-substituted α-GalCer analogues bearing p-nitro- (32), p-tert-butyl (34), or o-, m-, or p-methyl groups (40-42) displayed higher IFN-γ/IL-4 secretion ratios than α-GalCer in vitro. In mice, compound 16, with an 11-(3,4-difluorophenyl)undecanoyl acyl chain, induced significant proliferation of NK and DC cells, which should be beneficial in killing tumors and priming the immune response. These new glycolipids might prove useful as adjuvants or anticancer agents.

METHODS FOR PREPARATION OF GLYCOSPHINGOLIPIDS AND USES THEREOF

Methods for synthesis and preparation of alpha-glycosphingolipids are provided. Methods for synthesis of α-galactosyl ceramide, and pharmaceutically active analogs and variants thereof are provided. Novel alpha-glycosphingolipids are provided, wherein the compounds are immunogenic compounds which serve as ligands for NKT (natural killer T) cells.

Introduction of aromatic group on 4′-OH of α-GalCer manipulated NKT cell cytokine production

The glycosphingolipid α-GalCer has been found to influence mammalian immune system significantly through the natural killer T cells. Unfortunately, the pre-clinical and clinical studies revealed several critical disadvantages that prevented the therapeutic application of α-GalCer in treating cancer and other diseases. Recently, the detailed illustration of the CD1d/α-GalCer/NKT TCR complex crystal structural, together with other latest structural and biological understanding on glycolipid ligands and NKT cells, provided a new platform for developing novel glycolipid ligands with optimized therapeutic effects. Here, we designed a series of novel aromatic group substituted α-GalCer analogues. The biological activity of these analogues was characterized and the results showed the unique substitution group manipulated the immune responses of NKT cells. Computer modeling and simulation study indicated the analogues had unique binding mode when forming CD1d/glycolipid/NKT TCR complex, comparing to original α-GalCer.

Modification of the ceramide moiety of isoglobotrihexosylceramide on its agonist activity in stimulation of invariant natural killer T cells

Isoglobotrihexosylceramide (iGb3) is an endogenous antigen of mammalian cells and can stimulate invariant natural killer T (iNKT) cells to evoke autoimmune activities by the release of T helper 1 (Th1) and Th2 cytokines. Th1 cytokines are correlated with the antitumor and antiviral response, while Th2 cytokines are correlated with the amelioration of autoimmune diseases. iGb3 is a very weak agonist compared to the exogenous α-galactosylceramide; however, modification of the ceramide moiety has been advocated as one of the approaches to improve its stimulatory activity and to change the bias of release of Th1 and Th2 cytokines. Two analogues of iGb3, 2H-iGb3 and HO-iGb3 with different ceramide moieties, were synthesized. Bioassay results showed that HO-iGb3 was much more effective in stimulating iNKT cells than iGb3 at low concentration. The assay also showed that the CD1d/2H-iGb3 complexes are remarkably efficient in stimulating iNKT cells.

Synthesis of α-galactosyl ceramide and the related glycolipids for evaluation of their activities on mouse splenocytes

Phytosphingosine and its short-chain analog were efficiently synthesized with 19% overall yield in 10 steps, respectively, starting from an inexpensive d-lyxose. Galactosyl donors of sulfide and phosphite types bearing benzoyl protecting groups of 4- and

HEPATITIS C VIRUS INHIBITOR COMPRISING ALPHA-GLYCOSYLCERAMIDE AS THE ACTIVE INGREDIENT

This invention provides a growth inhibitor of human hepatitis C virus comprising, as an active ingredient, α-glycosylceramide used for patients infected with the aforementioned viruses. This inhibitor of hepatitis C virus comprises, as an active ingredien

Immunomodulatory α-Galactoglycosphingolipids: Synthesis of a 2′-O-Methyl-α-Gal-GSL and Evaluation of Its Immunostimulating Capacity

The total synthesis of 1-2-docosanoylamino-O-(2-O-methyl-α -D-galactopyranosyl)-1,3,4-octadecanetriol (2), a 2′-methoxy analog of the immunostimulating α-galactoglycosphingolipid 1, is reported. Stereoselective α-glycosylation of the azido precursor of sp

Synthesis of D-erythro-ceramide-1-phosphoinositol and its aminoglucosylated derivative - Intermediates in GPI-anchor biosynthesis

The readily available 2,3:4,5-di-O-cyclohexylidene-D-myo-inositol derivative 3 was converted into the 1-O-unprotected D-myo-inositol derivative 6. Reaction with the phosphite derivative 7 of 3-O-tert-butyldimethylsilyl-protected ceramide furnished the target molecule D-erythro-ceramide-1-phosphoinositol (1). Reaction of O-(3,4,6-tri-O-acetyl-2-azido-β-D-glucopyranosyl)trichloroacetimidate (20) with 3 gave exclusively α(1→6)-connected glycoside 21 which was converted into the 1α-O-unprotected derivative 24. Reaction with the D-erythro-azidophytosphingosine-derived ceramide-1-phosphite derivative 17 led, after oxidation and removal of the cyanoethyl group, to protected 2-azido-D-glucopyranosyl-α(1→6)-D-myo-inositol-1-phospho-ceramide (25) which could bo fully deprotected in two steps to afford the target molecule, the ceramide derivative of 2-amino-2-deoxy-D-glucopyranosyl-α(1→6)-D-myo-inositol-1-phosphate (2).

Practical Total Synthesis of (2S,3S,4R)-1-O-(α-D-Galactopyranosyl)-N-hexacosanoyl-2-amino-1,3,4- octadecanetriol, the Antitumorial and Immunostimulatory α-Galactosylceramide, KRN7000

A practical total synthesis of (2S,3S,4A)-1-O-(α-D-galactopyranosyl)-N-hexacosanoyl-2-amino-1,3,4- octadecanetriol (KRN7000), an antitumorial and immunostimulatory glycosphingolipid derived from agelasphins, was achieved in 14 steps starting from D-lyxose in a 16% overall yield.