Synthesis lipid mixture preparation

In human applications, lipid mixtures for archaeosome preparations have to be well defined and reproducibly produced. It is therefore of importance to be able to obtain pure lipids by controlling both the structure of the lipidic core and that of the polar heads. Total synthesis of archaeal lipid analogues was investigated by several research teams. More convenient synthetic approaches have been developed, of particular interest is the work developed by the Benvegnu team who demonstrated that acyclic tetraethers retained the main structural features of natural archaeal cyclic tetraether lipids (Fig. 31). ... 

The lipo-amino acids are generally synthesized as racemic mixtures which are resolved into optically pure a-amino acids by chemical or enzymatic methods.113" 137 133 The synthesis is based on the alkylation of diethyl acetamidomalonate followed by hydrolysis and decarboxylation. 129 138 140 Also, 20% DMF has been used in the hydrolysis step, as it is suitable for industrial scale preparation. 138] Alternatively, lipidated a-amino acids are synthesized by reacting a-bromoalkanoic acid with ammonium hydroxide. 141 ... 

Lipids also show asymmetrical distributions between the inner and outer leaflets of the bilayer. In the erythrocyte plasma membrane, most of the phosphatidylethanolamine and phosphatidylserine are in the inner leaflet, whereas the phosphatidylcholine and sphingomyelin are located mainly in the outer leaflet. A similar asymmetry is seen even in artificial liposomes prepared from mixtures of phospholipids. In liposomes containing a mixture of phosphatidylethanolamine and phosphatidylcholine, phosphatidylethanolamine localizes preferentially in the inner leaflet, and phosphatidylcholine in the outer. For the most part, the asymmetrical distributions of lipids probably reflect packing forces determined by the different curvatures of the inner and outer surfaces of the bilayer. By contrast, the disposition of membrane proteins reflects the mechanism of protein synthesis and insertion into the membrane. We return to this topic in chapter 29. 

To deduce the location of the double bond within the lipid backbone, the mixture (500 ng) was subjected to consecutive bisthiomethylation of the alkene85 and O-methyloxime formation (Equation 3). GC—MS study of the fragmentation of these derivatives (e.g., see 31, derived from 24) allowed simultaneous determination of the cleavage site (between C24 and C25) and of which portion contained the original ketone (i.e., the odd versus even mass fragments of 17 3 and 426 for 31). All of the monounsaturated lipid ketones had the alkene in the same downstream location in other words, they varied in the number of methylene units between the ketone and alkene functional groups but were constant in their -octyl terminal alkyl moiety. The four most major components (24, 25, 27, and 28) were prepared by chemical synthesis and used to confirm their identity in the natural pheromone and their pheromonal activity both alone and in admixtures. 

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