Large-scale synthesis solid phase

In addition, a novel fluorous support has been developed recently as an alternative to traditional polymer supports and applied successfully to oligosaccharide synthesis in combination with the trichloroacetimidate method [541]. Each intermediate in the fluorous oligosaccharide synthesis [542,543] could be obtained by simple fluorous-organic solvent extraction, and the reactions could be monitored by TLC, NMR and MS, in contrast to solid-phase reactions. Moreover, the new liquid-phase technique is anticipated to be easily applicable to the large-scale synthesis. 

In large-scale synthesis, quantitation is done by purifying and weighing the product. In solid-phase synthesis, there is often a submilligram yield that cannot be quantified by weighing. LC/UV/MS is often used to quantify libraries. However, when working with small amount of combichem com-... 

In order to achieve good-quality synthesis on a large scale, proper setting of the instrument is an integral part of the process. Here, large-scale synthesis of oligonucleotides on solid-phase has been discussed using a model 8800 DNA synthesizer. The instrument 8800 DNA synthesizer consists of different components ... 

In conclusion, compared with solution-phase synthesis, solid-phase enzymatic synthesis, generally, needs higher concentrations of enzyme, longer reaction times, and a large excess of donors. Although there is still room for improvement in terms of yields and scale-up of syntheses, in solid-phase synthesis purification procedures are straightforward so it is expected that this approach will open the route to automated oligosaccharide synthesis in the near future. 

Synthetic organic polymers, which are used as polymeric supports for chromatography, as catalysts, as solid-phase supports for peptide and oligonucleotide synthesis, and for diagnosis, are based mainly on polystyrene, polystyrene-divinylbenzene, polyacrylamide, polymethacrylates, and polyvinyl alcohols. A conventional suspension of polymerization is usually used to produce these organic polymeric supports, especially in large-scale industrial production. 

TsOH, THF, CH2CI2, 5 min. This method was developed for solid-phase peptide synthesis as a safe large-scale alternative to the use of TFA, which is expensive, corrosive, and a waste problem on a large scale." ... 

V Caciagli, F Cardinali, F Bonelli, P Lombardi. Large-scale production of peptides using the solid phase continuous flow method. Part 2 Preparative synthesis of a 26-mer peptide thrombin inhibitor. J Pept Sci 4, 327, 1998. 

Still, a lot needs to be done to develop large monolithic units, which would handle kilogram and larger production scales and guarantee to the process managers the stability of the support and its presence on the market over several decades. However it is realistic to expect that SMC will attract widespread use within a decade in a variety of applications, from chromatography to bioconversions, solid phase extractions and solid phase synthesis. 

Syntheses on solid phase can, in principle, be performed with standard equipment for organic synthesis. This is, however, only justifiable if large amounts of support are being handled. For small-scale preparations or for the development of solid-phase synthetic methodology, the simplicity of solid-phase synthesis should be fully exploited by conducting experiments in parallel. This requires more systematic planning of the experiments, but will be amply rewarded by the number of results obtained. 

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