The synthesis of regiospecifically 13C-labeled compounds of a biosynthetic precursor of lipid A and its analogue with shorter acyl chains is described. d-(6-13C)Glucose was converted into a suitably protected glucosamine derivative via 1,6-anhydro-β-d-(6-13C)glucose. After coupling with glycosyl donors, the desired compounds were synthesized through a 6-step reaction sequence. The total yields were 1.7% for the biosynthetic precursor, and 6.4% for the short acyl analogue, respectively, for a total of 18 steps from d-(6-13C)glucose.

[reaction: see text] A traceless solid-phase synthesis of substituted phthalimides is proposed. The target compounds are obtained within minutes by a microwave-assisted cyclative cleavage in good yields and excellent purities.

The detailed conformational analysis of a single molecule of the tetraacyl biosynthetic precursor-type lipid A and its characteristic supramolecular assembly in aqueous SDS-micelles are described. Regular molecular arrangements were observed by detailed analysis of the NMR spectra of synthetically pure specimens, including regiospecifically 13C-labeled ones. NMR analysis of a biologically inactive precursor-type analogue with four shorter acyl chains demonstrated its conformational flexibility, indicating the importance of hydrophobic interactions for maintaining the conformation of such molecules.

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