Parallel purification

The two major approaches for HPLC purification are fast gradient separation and parallel purification. Yan et al.178 utilized the former (Figure 1.51). The purification lab received a 96-well plate containing synthesized products at 0.1 to 0.2 mmol/well. A Hydra 96-probe liquid handler prepared QC plates for all samples that were analyzed with a MUX-LCT eight-channel parallel LCMS instrument at a throughput of 2000 samples/day. Only samples with purities above 10% were purified on a... 

The second stage is the proof of principle In this phase, we take the initial theoretical library idea and begin to apply chemistry experiments to validate experimental designs and potential library schemes at this stage, one also evaluates the method of library production (solid/solution/hybrid phases). In this phase, which is usually the longest phase in any library production process, we will perform the initial experiments, optimize the chemical yields and purities, modify the experiments to generate easily removable by-products, which can be removed by traditional parallel purification methods (i.e. SPE, Resin capture), and determine the most feasible route to the final product. 

An increasing number of groups are generating libraries in which parallel reactions occur in solution. Until very recently, solution-based syntheses were primarily utilized for the preparation of simple structures. However, the introduction of resin-bound reagents, scavenger resins, and parallel purification schemes is allowing more complex chemistries to be performed in parallel solution format. 

Booth RJ, Hodges JC, Polymer-supported quenching reagent for parallel purification, J. Am. Chem. Soc., 119 4882-4886, 1997. 

Ion-exchange chromatography is based on this principle and has been widely used for analytical purposes, while its application in organic synthesis has been limited to scattered examples, despite its simplicity and applicability to many separation problems. When the SP is an ion-exchange resin and the product has basic or acid functions, SPE should be considered the separation technique of choice. A number of examples from the recent literature serve to illustrate the applicability of the technique to parallel purification of a number of compounds. 

J. Isbell, R. Xu, Z. Cai, and D. B. Kassel, Realities of high-throughput liquid chromatography/mass spectrometry purification of large combinatorial libraries A report on overall sample throughput using parallel purification, 4 (2002), 600-611. 

RJ Booth, JC Hodges. Polymer supported quenching reagents for parallel purification. Am Chem Soc 119 4882,1997. 

SH DeWitt. Automated parallel purification methods. Solid and Solution Phase Combinatorial Synthesis, New Orleans, 1997. 

P Coffey. Parallel purification for combinatorial chemistry. Lab Autom News 2 7-13, 1997. 

Xu, R. Wang, T. Isbell, J. Cai, Z. Sykes, C. Brailsford, A. Kassel, D.B. High-Throughput Mass-Directed Parallel Purification Incorporating a Multiplexed Single Quadrupole Mass Spectrometer, Anal. Chem. 74(13), 3055-3062 (2002). 

Isbell, J. Xu, R. Cai, Z. Kassel, D.B. Realities of High-Throughput Liquid Chromatography/Mass Spectrometry Purification of Large Combinatorial Libraries A Report on Overall Sample Throughput Using Parallel Purification, J. Comb. Chem. 4, 600-611 (2002). 

The level of purity as well as the required amount of compound is generally imposed by the targeted biological evaluation. The crude cleavage product, however, often does not meet the purity requirement. To allow quick parallel purification and structural assessment an increasing amount of apparatus, softwares and techniques are required in laboratories. The most efficient is probably fast LC/MS and its multicolumn evolution that enables purification of hundreds of compounds a day. Similarly, parallel chromatography devices and TLC spotting apparatus can be found on the market. ... 

Fig. 4 Continuous dialysis apparatus for the parallel purification of up to twelve samples...

Several groups reported the use of ion exchange resins for the parallel purification of small-molecular-weight compound libraries. Reaction conditions for the synthesis of the library are chosen such that the product of interest has distinctly different physical properties than the byproducts or the excess reagents. 

Solid-phase extraction (SPE) is the method of sample preparation that concentrates and purifies analytes from solution by sorption onto a disposable solid-phase cartridge, followed by elution of the analyte with an appropriate solvent. The SPE technique was developed in the mid-1970s as an alternative means of liquid-liquid extraction but become particularly attractive for its automation, parallel purification, and pre-concentration. Since 1995, SPE has been applied in various fields, environmental, food sciences, biomedical analyses, pharmaceutical analyses, and organic synthesis. " There are a numbers of publications and reviews on the subjects of development of new solid-phase supporting materials, instrumentation and device, techniques, and theoretical aspect. ... 

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