Lipids chemical synthesis

Rasmussen JAM, Hermetter A (2008) Chemical synthesis of fluorescent glycero- and sphingolipids. Prog Lipid Res 47 436-460... 

Liposomes are colloidal particles that can be prepared with (phospho)-lipid molecules derived from either natural sources or chemical synthesis (recently reviewed by Lian and Ho [14]). The potential application of liposomes as biodegradable or biocompatible drug carriers to enhance the potency and reduce the toxicity of therapeutic agents was recognized in 1960. In the 1960s and 1970s various methods for liposome preparation were developed as... 

LPS immunotherapy was the first immunotherapy for cancers assayed in patients in spite of its toxicity. The standardisation of animal models of cancer, the discovery of the LPS composition and of lipid A activity, the discovery of lipid A structure leading to its chemical synthesis, and the synthesis of lipid A derivatives far less toxic than the natural lipids A, restarted research in this field. At the same time, advances in immunology allowed a better understanding of the mechanisms of action of LPS and lipids A in whole organisms. 

This subject has been of continuing interest for several reasons. First, the present concepts of the chemical constitution of such important biopolymers as cellulose, amylose, and chitin can be confirmed by their adequate chemical synthesis. Second, synthetic polysaccharides of defined structure can be used to study the action pattern of enzymes, the induction and reaction of antibodies, and the effect of structure on biological activity in the interaction of proteins, nucleic acids, and lipides with polyhydroxylic macromolecules. Third, it is anticipated that synthetic polysaccharides of known structure and molecular size will provide ideal systems for the correlation of chemical and physical properties with chemical constitution and macromolecular conformation. Finally, synthetic polysaccharides and their derivatives should furnish a large variety of potentially useful materials whose properties can be widely varied these substances may find new applications in biology, medicine, and industry. 

In recognition of the difficulty in obtaining the lipid intermediates in quantities to facilitate detailed mechanistic study of the peptidoglycan biosynthetic enzymes, we initiated an effort directed toward a chemical synthesis of both lipid I and lipid II. As was the case with the fermentation/isolation protocols, we anticipated several technical challenges that would need to be addressed in order to reach the target compounds. These challenges, and their solutions, will be discussed in the sections that follow. 

The initial target for our chemical synthesis of lipid I was phosphomuramyl pentapeptide 9. At the outset, we were confident in our ability to prepare the monosaccharyl pentapeptide core structure, but were unsure of our ability to install the anomeric phosphate with the desired a-stereochemistry. We were also concerned about the timing for introduction of the anomeric phosphate since solubility and anomeric selectivity could be strongly influenced by the presence or absence of the peptapeptide side chain. In addition, we had not settled on a method for... 

In summary, we were able to develop a chemically robust synthetic route to lipid I, the penultimate intermediate utilized in bacterial cell wall biosynthesis. The identification of a method for stereoselective introduction of the anomeric phosphate and a protocol to enable diphosphate coupling were pivotal to our success and ultimately provided the precedent for our chemical synthesis of lipid II detailed in the sections that follow. 

Galanos, C., Luderitz, O., Kusumoto, S., and Shiba, T. (1983). The chemistry of bacterial lipopolysaccharides with emphasis on the structure and chemical synthesis of their lipid A component. In Handbook of Natural Toxins, Vol II, Bacterial Toxins (Tu, Habig and Hardegree, eds.) Marcel Dekker, Inc., New York. 

Chemical Synthesis of Lipid A for the Elucidation of Structure-Activity Relationships... 

Paltauf, F. (1983) Chemical synthesis of ether lipids, in Ether Lipids. Biochemical and Biomedical Aspects, H. K. Mangold and F. Paltauf, editors, Academic Press, New York, pp. 49-84. 

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. 

Chemistry and Chemical Reactivity of Proteins Struemre, Function and Stability of Proteins Lipidated Peptide Synthesis Synthesis of Natural and Unnatural Amino Acids... 

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