Lipid total synthesis

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

TOTAL SYNTHESIS OF LIPID I AND LIPID II LATE-STAGE INTERMEDIATES UTILIZED IN BACTERIAL CELL WALL BIOSYNTHESIS... 

At this point, we had achieved access to an orthogonally protected phosphomuramyl pentapeptide derivative poised to enable completion of our lipid I total synthesis. The technical hurdles that remained to be addressed were 1) identification of a mild method for installation of the lipid diphosphate linkage, 2) global deprotection, and 3) final purification of our synthetic lipid I. Our solutions to these problems are addressed in the following section. 

The isolation of mutants in S. typhimurium by Rick and Osborn (11,12) and mutants in E. coli by Nishijima and Raetz (44) that accumulate the Lipid A precursor indicate that KDO synthesis and Lipid A synthesis are not coordinately controlled. The initial steps in the synthesis of the Lipid A precursor are totally unknown. The temperature sensitive mutants of E. coli isolated by Nishijima and Raetz (44) that are defective in phosphaditylglyc-erol phosphate synthesis at 42°C and accumulate the Lipid A precursors indicate that there is some relationship between the synthesis of phosphatidylglycerol and LPS. The reasons for the acu-cumulation of the Lipid A precursors in this E. coli mutant are not obvious. We have shown that CDP-diglyceride, one of the substrates for phosphatidylglycerol phosphate synthesis, is an inhibitor of D-arabinose-5-phosphate isomerase with an 1 value... 

Figure 15. Proposed total synthesis of lipid A using the precursor 59 prepared as in...

The total synthesis of a novel hybrid lipid Pea-PIP2 (51), possessing a phosphatidyl ethanolamine (PE) headgroup at the 1-position and a phosphatidyl inositol 4,5-bisphosphate [PtdIns(4,5)P2] headgroup at the 4-position has been elaborated. Reporter groups (biotin, fluorophores, spin label) were... 

Eguchi, T., Ibaragi, K., Kakinuma, K. Total Synthesis of Archaeal 72-Membered Macrocyclic Tetraether Lipids. J. Org. Chem. 1998, 63, 2689-2698. 

Support has been obtained in experiments with natural thermo-zeaxanthin (22) containing mixed acyl residues [47] and with the pure z so-C15 0 acylated thermozeaxanthin (23), prepared by total synthesis, on a liposomal lipid bilayer [48]. 

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