Chiral separations technologies

Methyl diazoacetates were used extensively in earlier work because menthyl esters were amenable to separation by chromatographic methods. However, advances in chiral separation technologies have significantly reduced the need for chiral auxiliaries today, and enantiomeric separations of even simple esters are now routine. Selectivities obtained with menthyl diazoacetates are now of mainly historical interest. 

Figure 6.27 illustrates a sample chromatogram for racemic resolution on a MIP stationary phase, whilst Table 6.6 summarises the developments in the field of molecularly imprinted chiral separation technology. 

With all these applications a chiral separation must be developed, but, after, under two decades of rapid progress in commercially available chiral separation technology, the situation has now been reached that developing a suitable chiral separation is often the easiest part of the overall method development. 

Abel S, Juza M (2007) Less common applications of enantioslective HPLC using the SMB technology in pharmaceutical industry. In Subramanina G (ed) Chiral separation technologies, 3rd edn. Wiley-VCH, Weinheim, pp 203-273... 

Proteias, amino acids bonded through peptide linkages to form macromolecular biopolymers, used as chiral stationary phases for hplc iaclude bovine and human semm albumin, a -acid glycoproteia, ovomucoid, avidin, and ceUobiohydrolase. The bovine semm albumin column is marketed under the name Resolvosil and can be obtained from Phenomenex. The human semm albumin column can be obtained from Alltech Associates, Advanced Separation Technologies, Inc., and J. T. Baker. The a -acid glycoproteia and ceUobiohydrolase can be obtained from Advanced Separation Technologies, Inc. or J. T. Baker, Inc. 

Cyclodextrin stationary phases utilize cyclodextrins bound to a soHd support in such a way that the cyclodextrin is free to interact with solutes in solution. These bonded phases consist of cyclodextrin molecules linked to siUca gel by specific nonhydrolytic silane linkages (5,6). This stable cyclodextrin bonded phase is sold commercially under the trade name Cyclobond (Advanced Separation Technologies, Whippany, New Jersey). The vast majority of all reported hplc separations on CD-bonded phases utilize this media which was also the first chiral stationary phase (csp) developed for use in the reversed-phase mode. 

S. Ahuja (Ed.), Chiral Separations Applications and Technology, ACS, Washington DC, 1997. ISBN 0841234078. 

Abuja, S. Chiral Separations Applications and Technology American Chemical Society Washington D.C., 1997. 

Possible applications of MIP membranes are in the field of sensor systems and separation technology. With respect to MIP membrane-based sensors, selective ligand binding to the membrane or selective permeation through the membrane can be used for the generation of a specific signal. Practical chiral separation by MIP membranes still faces reproducibility problems in the preparation methods, as well as mass transfer limitations inside the membrane. To overcome mass transfer limitations, MIP nanoparticles embedded in liquid membranes could be an alternative approach to develop chiral membrane separation by molecular imprinting [44]. 

Brice, L. J., Pirkle, W. H., Chiral separations Applications and Technology, Ahuja, Satinder (eds.) American Chemical Society, Washington D.C., 1997... 

The availability of a new class of efficient separations technology for chiral drugs can have an impact on other business issues now at the forefront of the pharmaceutical industry. For example, the strategy of better drug life cycle management can be... 

Amino acid separations represent another specific application of the technology. Amino acids are important synthesis precursors - in particular for pharmaceuticals -such as, for example, D-phenylglycine or D-parahydroxyphenylglycine in the preparation of semisynthetic penicillins. They are also used for other chiral fine chemicals and for incorporation into modified biologically active peptides. Since the unnatural amino acids cannot be obtained by fermentation or from natural sources, they must be prepared by conventional synthesis followed by racemate resolution, by asymmetric synthesis, or by biotransformation of chiral or prochiral precursors. Thus, amino acids represent an important class of compounds that can benefit from more efficient separations technology. 

Erancotte E. (1996) Chromatography as a Separation Tool for the Preparative Resolution of Racemic Compounds, in Chiral Separations. Applications and Technology, Ahuja S. (ed.), American Chemical Society, p. 271-308. 

Chiral Separations by Liquid Chromatography and Related Technologies, Hassan Y. Aboul-Enein and Imran AH... 

Chirobiotic Handbook, Guide to using macrocyclic glycopeptide bonded phases for chiral LC separations, Advanced Separation Technologies Inc. (ASTEC), 2nd Ed. Whippany, New York... 

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