Supported synthesis

At the time of writing this book, SPOS is in an area of reladve infancy but has considerable potential. One of the main difficulties in SPOS lies in the lack of techniques available to monitor reacdons carried out on polymer supports. Unlike reacdons in solution phase, reactions on solid support cannot be monitored with relative ease and this has hindered the progress as well as the efficacy of solid supported synthesis of small non-peptidic molecules. Despite these difficulties, a large body of studies is available for SPOS. Recent reviews incorporate... 

Polymer-supported synthesis of natural macrocyclic lactones and other 0-heterocycles 99AG(E)1903. 

These conceptual goals are attained by several combinatorial methods and tools. Characteristic for combinatorial chemistry is the synthesis on solid support or by polymer-supported synthesis, allowing for much higher efficiency in library production. Synthesis can be conducted either in automated parallel synthesis or by split-and-recombine synthesis. Centerpieces of combinatorial methods further include specific analytical methods for combinatorial... 

Solid Phase Synthesis Versns Polymer-Supported Synthesis in Solution... 

Solid phase synthesis is a polymer-supported or solid-supported synthesis, i.e., stepwise construction of product molecules attached to an insoluble organic or inorganic polymer. 

Solid-phase chemistry is an efficient synthetic tool that, compared with solution-phase chemistry, simplifies the work-up of the reaction, allows the process to be driven to completion by using excess of reagents, and can be automatized [2a]. In recent years, many studies have been devoted to developing both surface-mediated and resin-supported synthesis. Today the solid-phase approach is not limited to peptides and oligonucleotides but is also used to synthesize molecules of lower molecular weight. 

The microwave-assisted solid-supported synthesis of 1,3,4-thiadiazoles was described applying from acid and thiosemicarbazide on acidic aliunina... 

Atherton E, Logan CJ, Sheppard RC, Peptide synthesis, part 2 Procedures for solid phase synthesis using W-lluorcnylmcthoxycarbon-ylamino acids on polyamide supports Synthesis of substance P and of acyl carrier protein 64—74 decapeptide. J Chem Soc Perkin Trans 1 1981 ... 

W. J. Hagan Jr. et al. have reported the cyanate-supported synthesis of pyrophosphate from CaHPCL -2 H2O. Relatively low concentrations (5-20 mM) of NaOCN were required. The experiments show that the solubility of CaHPC>4 2 H2O is dependent on the pH value of the solution and the total concentration of Ca2+ NaCl, however, has only a little influence (Hagan et al., 2007). 

Collioud, A., Clemence, J.-F., Sanger, M., and Sigrist, H. (1993) Oriented and covalent immobilization of target molecules to solid supports Synthesis and application of a light-activatable and thiol-reactive cross-linking reagent. Bioconjugate Chem. 4, 528-536. 

In another application, the group of Berteina-Raboin demonstrated the solid-supported synthesis of the indole core of melatonin analogues under microwave irradiation (Scheme 7.6) [26]. A benzoic acid derivative was coupled to Rink amide resin by... 

Scheme 7.12 Reaction strategies for the polymer-supported synthesis of dialkylaminopropenones.

A very interesting approach toward solid-supported synthesis under microwave heating was introduced by Chandrasekhar and coworkers [64], The authors developed a synthesis of N-alkyl imides on a solid phase under solvent-free conditions employing tantalum(V) chloride-doped silica gel as a Lewis acid catalyst (Scheme 7.53). 

Grafted Ionic Liquid-Phase-Supported Synthesis... 

Scheme 12.19 Ionic liquid-phase supported synthesis performed with microwave irradiation.

Table 16 Traceless polymer-supported synthesis of 4,5-disubstituted 3-amino-1,2,4-triazole derivatives (Scheme 5)...

William Fraser was born in Hamilton. He studied at the other of the two local universities, Strathclyde, where he obtained a first class B.Sc. honors degree in 1986 and Ph.D. in 1989 under the direction of Professor Colin J. Suckling and Professor Hamish C. S. Wood. He was awarded a Royal Society European Exchange Postdoctoral Fellowship and worked in the laboratories of Professor Albert Eschenmoser at the ETH, Zurich. In 1991, he took up his present position as lecturer in medicinal chemistry at Aston University, Birmingham. His scientific interests include nucleoside and nucleic acid chemistry, solid-supported, synthesis, and study of base-modified antigene oligonucleotides targeted to DNA. 

Highly efficient modifications of Mukaiyama s procedure, convenient for combinatorial syntheses, were reported recently, namely the polymer-supported synthesis of isoxazolines via nitrile oxides, starting from primary nitroalkanes, in a one-pot process (75) and by microwave activation of the process (73). 

Solid-Phase Supported Synthesis A Possibility for Rapid Scale-Up of Chemical Reactions... 

After isolating the product of a solid phase synthesis, the support (resin + linker) is usually discarded as waste, although successful examples of its reuse in further synthetic cycles are known with trityl type linkers (Frechet and Haque 1975). To reduce both volume of operation and amount of waste, the loading of the resin (quantified as millimoles of functionality per gram) has to be increased. Besides theoretical limitations (for polystyrene this is reached when every phenyl ring is substituted by the linker), there may be practical boundaries for using highly loaded resins in solid-phase supported synthesis. This issue was studied... 

In summary, we demonstrated the possibility of the fast scale-up of solid-phase supported synthesis. In one case (pyrimidine derivate), the research protocols could be used directly with only minor modifica-... 

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