- Alpha-GalCer phosphate compounds with immunocompetence and synthesis method thereof
-
The invention discloses alpha-GalCer phosphate compounds with immunocompetence and a synthesis method thereof, and belongs to the technical field of organic synthesis. The invention is technically characterized in that: the alpha-GalCer phosphate compound
- -
-
Paragraph 0027; 0028
(2018/01/19)
-
- Efficient Divergent Synthesis of New Immunostimulant 4″-Modified α-Galactosylceramide Analogues
-
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
- Janssens, Jonas,Decruy, Tine,Venken, Koen,Seki, Toshiyuki,Krols, Simon,Van Der Eycken, Johan,Tsuji, Moriya,Elewaut, Dirk,Van Calenbergh, Serge
-
supporting information
p. 642 - 647
(2017/06/13)
-
- A comparison of benzyl and 2-naphthylmethyl ethers as permanent hydroxyl protecting groups in the synthesis of α-galactoglycosphingolipids KRN7000 and PBS-57
-
Due to the interest in the biological properties of marine derived α-galactoglycosphingolipids (α-GalGSLs), a lot of work has focused on the development of their synthesis. Here we conducted the direct comparison of benzyl and 2-naphthylmethyl (Nap) ether
- Yao, Dongming,Liu, Yichu,Gao, Qi,Sui, Qiang,Liu, Xiaoping,Ding, Ning
-
p. 173 - 188
(2017/10/13)
-
- 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.
- Hsieh, Ming-Han,Hung, Jung-Tung,Liw, Ya-Wen,Lu, Yin-Jen,Wong, Chi-Huey,Yu, Alice L.,Liang, Pi-Hui
-
p. 1689 - 1697
(2012/09/21)
-
- 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.
- Zhang, Wenpeng,Xia, Chengfeng,Nadas, Janos,Chen, Wenlan,Gu, Li,Wang, Peng George
-
experimental part
p. 2767 - 2776
(2011/06/19)
-
- Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000
-
(Chemical Equation) The synthesis of 4-deoxy-4,4-difluoro-KRN7000 starting from phytosphingosine is described. Key steps include a regioselective benzylation of azidophytosphingosine and a deoxofluor-mediated fluorination of the corresponding 4-ketone. Th
- Leung, Leo,Tomassi, Cyrille,Van Beneden, Katrien,Decruy, Tine,Elewaut, Dirk,Elliott, Tim,Al-Shamkhani, Aymen,Ottensmeier, Christian,Van Calenbergh, Serge,Werner, Joern,Williams, Tony,Linclau, Bruno
-
scheme or table
p. 4433 - 4436
(2009/05/26)
-
- 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.
- Xia, Chengfeng,Schümann, Jens,Emmanuel, Rossy,Zhang, Yalong,Chen, Wenlan,Zhang, Wenpeng,De Libero, Gennaro,Wang, Peng George
-
p. 3489 - 3496
(2008/02/08)
-
- Efficient synthesis of D-erythro-sphingosine and D-erythro-azidosphingosine from D-ribo-phytosphingosine via a cyclic sulfate intermediate
-
The synthesis of naturally occurring D-erythro-sphingosine and synthetically useful D-erythro-2-azidosphingosine from commercially available D-ribo-phytosphingosine is described. An important feature of this synthesis is the selective transformation of the 3,4-vicinal diol of phytosphingosine into the characteristic E-allylic alcohol of sphingosine via a cyclic sulfate intermediate.
- Kim, Sanghee,Lee, Sukjin,Lee, Taeho,Ko, Hyojin,Kim, Deukjoon
-
p. 8661 - 8664
(2007/10/03)
-
- 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
- Fan, Gang-Ting,Pan, Yi-Shin,Lu, Kuo-Cheng,Cheng, Yu-Pei,Lin, Wan-Chen,Lin, Steven,Lin, Chun-Hung,Wong, Chi-Huey,Fang, Jim-Min,Lin, Chun-Cheng
-
p. 1855 - 1862
(2007/10/03)
-
- Efficient synthesis of α-galactosyl ceramide analogues using glycosyl iodide donors
-
(Chemical Equation Presented) The combination of reactive galactosyl iodide donors with electron-rich acceptor lipids provides highly stereoselective and efficient routes to α GalCer analogues. Using per-O-silylated donors, key intermediates can be obtain
- Du, Wenjun,Gervay-Hague, Jacquelyn
-
p. 2063 - 2065
(2007/10/03)
-
- 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
- -
-
Page/Page column 14
(2010/02/11)
-
- 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).
- Kratzer, Bernd,Mayer, Thomas G.,Schmidt, Richard R.
-
p. 291 - 298
(2007/10/03)
-
- 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.
- Morita, Masahiro,Sawa, Eiji,Yamaji, Kazuo,Sakai, Teruyuki,Natori, Takenori,Koezuka, Yasuhiko,Fukushima, Hideaki,Akimoto, Kohji
-
p. 288 - 292
(2007/10/03)
-