Synthesis of Ten Members of the Maradolipid Family; Novel Diacyltrehalose Glycolipids from Caenorhabditis elegans

Abstract

The synthesis of ten members of the maradolipid family is described using a direct route starting from trehalose.

The Synthesis and Biological Evaluation of Ligands for C-Type Lectin Receptors

“…Maradolipids consist of a mixture of symmetrical and asymmetrical glycolipids containing mainly iso-branched and straight chain fatty acids (45, Figure 2.1). 125,128 Several syntheses of asymmetric maradolipids have been reported, [128][129][130][131] syntheses of asymmetric maradolipids via the use of 2,2',3,3',4,4'-hexa-O-trimethylsilyl trehalose as an intermediate. 128,131 This intermediate was appealing due to its convenient synthesis and the ease at which labile trimethylsilyl (TMS) protecting groups can be removed following esterification.…”

“…125,128 Several syntheses of asymmetric maradolipids have been reported, [128][129][130][131] syntheses of asymmetric maradolipids via the use of 2,2',3,3',4,4'-hexa-O-trimethylsilyl trehalose as an intermediate. 128,131 This intermediate was appealing due to its convenient synthesis and the ease at which labile trimethylsilyl (TMS) protecting groups can be removed following esterification. 131,132 coupling reagents to provide the monoacyl derivative.…”

“…131,132 coupling reagents to provide the monoacyl derivative. 128 The second acylation of the monoester was achieved by reaction with an excess of the second fatty acid under similar conditions to give the diacyl derivative. Desilylation of the diacylated protected trehalose analogues with TFA and subsequent purification by HPLC afforded the unsymmetrical maradolipids in five steps and in 34-40% overall yield.…”

“…By using an excess of 13-methyltetradecanoic acid, the symmetric maradolipid 6,6'-di-O-13-methyltetradecanosanoyl-α,α'-D-trehalose was synthesised in 55% overall yield. 128 benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) in pyridine to yield the monoester in 65% yield. 129 The monoester was then further esterified (using fatty acids) to provide nonsymmetrical maradolipids in 59-81% yields.…”

“…134 Of these analogues, only the synthesis of 45b has been reported previously. 128 To determine how the presence of the iso-branch influences the immune response to the glycolipid, the C12, C14 and C18 linear chain trehalose diesters (TDEs) were also synthetic targets. Once synthesised, the ability of the glycolipids to activate murine BMDMs would then be explored.…”