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Efficient divergent synthesis of new immunostimulant 4″-modified α-galactosylceramide analogues

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Abstract
A synthesis strategy for the swift generation of 4"-modified alpha-galactosylceramide (alpha-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.
Keywords
CD1d, cytokine secretion, immunomodulators, KRN7000, Th1/Th2, α-Galactosylceramide, CELL STIMULATING PROPERTIES, GALCER ANALOGS, BENZYLIDENE ACETALS, CERAMIDE ANALOGS, ACTIVATION, RESPONSES, RECEPTOR, AGONISTS, LIGANDS, DONORS

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Citation

Please use this url to cite or link to this publication:

Chicago
Janssens, Jonas, Tine Decruy, Koen Venken, Toshiyuki Seki, Simon Krols, Johan Van der Eycken, Moriya Tsuji, Dirk Elewaut, and Serge Van Calenbergh. 2017. “Efficient Divergent Synthesis of New Immunostimulant 4″-modified Α-galactosylceramide Analogues.” Acs Medicinal Chemistry Letters 8 (6): 642–647.
APA
Janssens, Jonas, Decruy, T., Venken, K., Seki, T., Krols, S., Van der Eycken, J., Tsuji, M., et al. (2017). Efficient divergent synthesis of new immunostimulant 4″-modified α-galactosylceramide analogues. ACS MEDICINAL CHEMISTRY LETTERS, 8(6), 642–647.
Vancouver
1.
Janssens J, Decruy T, Venken K, Seki T, Krols S, Van der Eycken J, et al. Efficient divergent synthesis of new immunostimulant 4″-modified α-galactosylceramide analogues. ACS MEDICINAL CHEMISTRY LETTERS. 2017;8(6):642–7.
MLA
Janssens, Jonas, Tine Decruy, Koen Venken, et al. “Efficient Divergent Synthesis of New Immunostimulant 4″-modified Α-galactosylceramide Analogues.” ACS MEDICINAL CHEMISTRY LETTERS 8.6 (2017): 642–647. Print.
@article{8520058,
  abstract     = {A synthesis strategy for the swift generation of 4{\textacutedbl}-modified alpha-galactosylceramide (alpha-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{\textacutedbl}-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.},
  author       = {Janssens, Jonas and Decruy, Tine and Venken, Koen and Seki, Toshiyuki and Krols, Simon and Van der Eycken, Johan and Tsuji, Moriya and Elewaut, Dirk and Van Calenbergh, Serge},
  issn         = {1948-5875},
  journal      = {ACS MEDICINAL CHEMISTRY LETTERS},
  language     = {eng},
  number       = {6},
  pages        = {642--647},
  title        = {Efficient divergent synthesis of new immunostimulant 4{\textquotedbl}-modified \ensuremath{\alpha}-galactosylceramide analogues},
  url          = {http://dx.doi.org/10.1021/acsmedchemlett.7b00107},
  volume       = {8},
  year         = {2017},
}

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