Immunomodulatory α‐Galactoglycosphingolipids: Synthesis of 2'‐Fluoro‐2'‐deoxy‐α‐galactosylceramide and an Evaluation of Its Immunostimulating Properties

Abstract

In the framework of a project to assess the immunomodulating properties of α‐galactosyl glycosphingolipids, the total synthesis of 1‐O‐(2‐fluoro‐2‐deoxy‐α‐D‐galactopyranosyl)‐2‐docosanoylamino‐1,3,4‐octadecanetriol (1), a 2'‐fluoro analogue of the immunostimulating α‐galactoglycosphingolipids, was accomplished. The glycosidation reaction of the azido precursor of sphingosine was performed using the Mukaiyama glycosidation reaction. The stimulation of mouse splenocyte proliferation by the 2'‐fluoro analogue was highly reduced compared to that of the α‐galactoglycosphingolipids, thereby confirming that a free galactose 2‐OH group is essential for the immunostimulatory activity. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

New Principles for Glycoside‐Bond Formation

“…A similar situation was encountered in the activation of 2-fluoroglycosyl donors. [226] Moderate to good b selectivities were also observed in the glycosylation of a range of acceptors with rhamnosyl donors protected with sulfonyl groups at the 2-O-position, as exemplified in Scheme 21 b by the reaction of 148.…”

Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry

“…5 The equatorial C2–OH group of the galactose was also found to be crucial for the activity of α-GalCer; any modification at this position largely abolished activity. 6 Modifications at the C3- and C6–OH groups of the galactose was found to be tolerated. 7 The structure–activity relationship (SAR) studies centered on the ceramide moiety of α-GalCer may be grouped into modifications of the acyl and phytosphingosine chains, and of the polar portion of the ceramide.…”

Structure-Activity Relationship Studies of Novel Glycosphingolipids That Stimulate Natural Killer T-Cells

“…[22][23][24] Therefore, the former three hydroxy groups seem to play important roles in making a stable CD1d-antigen-TCR complex and hence show the potent immunostimulatory activities. Indeed, many analogs have been developed by modification of the three former hydroxy groups to other functional groups, for example, H (deoxy), F, N 3 , NH 2 , NHAc, OMe, and O(CH 2 ) 2 OH, 46,[104][105][106][107][108][109] but none of these analogs showed potent bioactivities, except for the 3-O-sulfo--galactosyl analog of 1 (37, Fig. 6), 105,110,111) and the 4-O-phenylpropyl--galactosyl analog (Ar3-GSL, 38).…”