Synthesis precipitation-driven

N Y 0 Precipitation-driven synthesis of peptides in organic solvent. 

N Y Eutectic melting A Precipitation-driven synthesis of peptides in aqueous phase. Two solid substrates form a liquid phase by eutectic melting. 

Precipitation-driven reactions show some very favorable advantages when compared to other low-water systems for enzymatic synthesis of peptides [55, 56]. 

The solid-to-solid approach clearly combines the good rates observed in aqueous solution, with the high yields typical of biocatalysis in organic solvents. Many successful examples of precipitation-driven reactions for the synthesis of peptides have been published in recent years (Table 12.3). 

Table 12.4 Precipitation-driven biocatalysis for the synthesis of peptides, catalyzed by proteases, in the presence of organic solvents.

Uhjn RV, Janssen AEM, Moore BD et al. (2001) Predicting when precipitation-driven synthesis is feasible applications to biocatalysis. Chem Eur J 7 2089-2098. 

Zhang, W., Brombosz, S.M., Mendoza, J.L, and Moore, J.S. (2005) A high-yield, one-step synthesis of o-phenylene ethynylene cyclic trimer via precipitation-driven alkyne metathesis. 

Using guanosine or 2 -deoxyguanosine as starting material for the synthesis of ribonucleosides or deoxyribonucleosides respectively, the reaction can be driven towards completion by precipitation of the highly insoluble guanine co-product. This approach has... 

Because the oxidation potential of the polymer is lower than that of the monomer, the polymer is electrochemically oxidized into a conducting state, kept electrically neutral by incorporation of the electrolyte anion as a counter-ion. This is an essential since precipitation of the unoxidized, insulating polymer would stop the reaction. Both coulometric measurements and elemental analysis show approximately one counter-ion per four repeat units. An important feature is the fact that the polymerization is not reversible whereas the oxidation of the polymer is. If the polymer film is driven cathodic then it is reduced towards the undoped state. At the same time neutrality is maintained by diffusion of the counter-ions out of the film and into the electrolyte. This process is reversible over many cycles provided that the film is not undoped to the point where it becomes too insulating. It is possible to use it to put new counter-ions into the film, allowing the introduction of ions which are too nucleophilic to be used in the synthesis. The conductivity of the film for a given degree of oxidation depends markedly on the counter-ion, varying by a factor of up to 105. 

Carbonates are a favorite in combination precipitation-decomposition reactions, but hydroxides are almost as common. In these precursors, the hydroxide is converted into water, which is driven off at elevated temperatures. For example, the synthesis of Fe304, or magnetite can be accomplished by precipitation the pe2+/3+ hydroxide, which with gentle heating is converted into the oxide ... 

Uniform and small crystallites could be rapidly synthesized by milling of crystal precursor. The size and concentration profiles of precipitated particles affected not only the induction period and the rate of crystallization, but also the crystal structure and distribution of the acid sites. Accordingly, if the crystal precursor is as small and uniform as possible, the synthesis of a very small and uniform crystallites and very rapid crystallization would be expected. Such small particles would play the role of nuclei of the crystals. Therefore, in this study, the precipitated gel was milled by a motor driven mortar. The liquid phase separated from the gel by the progress of milling was removed twice by centrifuge (Method 3) ... 

The synthesis of highly Tewis acidic fluorinated arylalu-minum compounds such as A1(C6F5)3 has been of interest in recent years,but efforts have been hindered by the proclivity of aluminum to abstract fluoride, often resulting in violent decomposition. The preferred synthesis of A1(C6F5)3 is by stirring commercially available B(C6F5)3 with MesAl at room temperature in toluene and hexanes (equation 19). The reaction does not go to completion but can be driven to do so by precipitation of the desired product as the toluene solvate... 

The solvent also influences the reaction through its effect on the relative soln-bility of substrate and product. Ideally, the substrate would be solubilized, while the insoluble product precipitates from solution. Thus, the recovery of product would be improved, thermodynamic equilibrium in the solvent phase would be driven toward ester synthesis, and product inhibition would be prevented. This scenario can occur for the lipase-catalyzed esterification of saccharides and nonpolar, saturated fatty acids. When employing polar solvents such as acetone, saccharides remain solubilized, while the product, saccharide-fatty acid monoester, precipitated. ... 

Prebiotic peptides, peptides formed before the origin of life. Most likely, amino acids were already present on primitive Earth. They are supposed to have been produced in the primitive atmosphere, in hydrothermal vents, or to have been imported in meterorites. a-Amino acids can undergo peptide formation by activation with carbon monoxide under hot aqueous conditions in the presence of freshly co-precipitated colloidal (Fe,Ni)S. Peptides may have been formed via —>-N-carboxy anhydrides. A replicative synthesis involving aminoacyl-RNA intermediates has also been suggested. The question of whether a peptide/protein world preceded the RNA-driven template synthesis, or whether RNA and proteins should not be viewed as eti-ologically discrete entities in the origin of life, is still under debate [V. Borsenberger et al., Chem. Biodivers. 2004, 1, 203 C. Huber et al., Science 2003, 301, 938 A. Brack, Chem. Biodivers. 2007, 4, 665]. 

In 1997, Harrison and coworkers reported on the synthesis of an azobenzene compound in microfluidic channels [37] for the purpose of combinatorial synthesis. The azo coupling of N,N-dimethylaniline and 4-nitrobenzene diazonium tetrafluor-oborate (Scheme 4.17) was carried out in a Pyrex microreactor driven by electro-osmotic flow. A few years later, Hisamoto et al. described a phase transfer diazo coupling reaction carried out in a microfluidic chip [38]. By providing a huge liquid-liquid interface between a solution of 5-methylresorcinol dissolved in ethyl acetate and an aqueous solution of 4-nitrobenzenediazonium tetrafluoroborate (Scheme 4.18), 100% conversion within a 2.3 s residence time was achieved. In contrast to macroscale experiments, the reaction could be accelerated and the formation of unwanted precipitates and bisazo side products was successfully suppressed. 

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