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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

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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

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