N-linked glycolipids by Staudinger coupling of glycosylated alkyl diazides with fatty acids

• Staudinger reaction enables synthesis of amide linked glyco-glycerolipid analogs.
• Steric hindrance can lead to Staudinger-based cyclization of 1,3-diazides.
• Amide analogs of glyco-glycero lipids exhibit very high Krafft temperatures.

Aiming for new glycolipids with enhanced chemical stability and close structural similarity to natural cell membrane lipids for the development of a drug delivery system, we have synthesized double amide analogs of glyco-glycerolipids. The synthesis applied a Staudinger reaction based coupling of a 1,3-diazide with fatty acid chlorides. While the concept furnished the desired glucosides in reasonable yields, the corresponding lactosides formed a tetrahydropyrimidine based 1:1 coupling product instead. This unexpected coupling result likely originates from steric hindrance at the iminophosphorane intermediate and provides an interesting core structure for potentially bioactive surfactants. The assembly behavior of both glycolipid types was investigated by optical polarizing microscopy, DSC and surface tension studies.

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