Chemical synthesis of bacterial lipid A

This chapter describes typical examples of recent chemical syntheses of lipid A analogues including both natural types corresponding to those obtained from bacterial cells and several artificial structural analogues related to the former. The targets of the syntheses mentioned in this chapter include both natural-type lipid A analogues as obtained from bacterial cells and several artificial structures related to the former. In the first instance, an overview of some key earlier published works has been provided, followed by a review of subsequent methodological improvements, which made the synthesis of this group of biologically interesting glycoconjugate molecules practical and efficient. Both ³H-labelled endotoxic and antagonistic lipid A analogues have been prepared and utilized for the study of their interactions with the receptor complex that induces innate immune responses of hosts on contact with LPS and lipid A. By the aid of modern methods of purification, lipid A analogues from various bacterial species have been isolated in high homogeneity and their structures readily elucidated by new powerful spectroscopic methods. The important role of chemical synthesis is to supply preparations completely free from any contaminants of bacterial origin and labeled or modified derivatives to be used as tracers or probes for biological investigations or spectroscopic conformational analyses.