Resolution of stereoisomers

The 0 -phenyl-0 -piperidyl-(2)-acetic acid methylester of BP 135° to 137°C under 0.6 mm pressure is obtained in theoretical yield by hydrogenation of 50 g of 0 -phenyl-0 -pyridyl-(2)-acetic acid methylester in glacial acetic acid in the presence of 1 g of platinum catalyst at room temperature, while taking up 6 hydrogen atoms. Reaction with HCI gives the hydrochloride. Resolution of stereoisomers is described in U.S. Patent 2,957,880. 

Chiral chromatography can also be used in order to obtain resolution of stereoisomers from aspartame, its precursors, and its degradation products. Lin et al. (84), using a Chiracel OD column and a mobile phase of 2-propanol -hexane (1 1, v/v), achieved complete separation of aspartame precursors, dd-, dl-, LL-, and LD-[(Z)-AspOS-Bzl)-Phe-OCH3], Motellier and Wainer (85) separated four stereoisomers of aspartame, two of diketopiperazine, and three of aspartyl-phenylalanine using a stationary phase composed of a chiral crown either coated on a polymeric support—CrownPack CR( + )—a mobile phase of aqueous perchloric acid, pH 2.8, and modified... 

S.L. Matson, Method for Resolution of Stereoisomers in Multiphase and Extractive Membrane Reactors, US Patent 4,800,162 (January, 1989). 

Examples in this chapter include sterile crystallization of a labile compound, yield enhancement by crystallization, yield and selectivity enhancement, removal of low-level impurities via crystallization from the melt, crystal formation in vials in a freeze drier, and non-equilibrium resolution of stereoisomers by crystallization. These examples represent unique crystallization processes designed for specific purposes. One lesson to be learned from examination of these nonmainstream applications is that understanding of principles can lead to inventive solutions to problems. For instance, in Examples 11-2 and 11-3, the solubility difference between starting material and desired product is used to optimize the reaction yield/selectivity by crystallizing the product and protecting it from overreaction. 

A brief discussion of processes introduced by Merck Company for kinetic resolution of stereoisomers by crystallization is included here. A more detailed description can be found in Chapter 11. 

For the synthesis, separation, and resolution of stereoisomers of 1,1 -(1,2-ethanediyl)bis(4,4-dimethyl-1--phenyl-1,2,3,4-tetrahydrophosphinolinium) diperchlorate, including the use of P-nmr analysis to monitor the resolution see Gurusamy and Berlin (ibid., p.3114). 

Concluding this short summary on the possibilities of the use of SLM technology for the resolution of stereoisomers, by proper choice of the... 

Enzymatic resolution of stereoisomers Carboxylic acid anilides from carboxylic acids... 

Selectivity and separation enhancement is achieved by modification of the buffer pH and by the addition such as chiral selectors for the resolution of stereoisomers and cyclodextrins to resolve sample components by differential transient complexation. 

The kinetic resolution of stereoisomer mixtures is a process based on the stereoselectivity of the enzyme, which speeds up the reaction selectivity that produces just one enantiomer the reaction equilibrium always prescribes the racemic solution formation, but continuously removing the isomers (distributed with a large excess of the enantiomer of interest) pushes back the reaction towards the formation of products of the speeded reaction. Thus, the removed solution is enriched by the enantiomer of interest if the reaction rate differences are great, the purity of the permeate solution is high with respect to the enantiomeric form of interest. 

Engineered enzymes have application in the resolution of stereoisomers, especially in the pharmaceutical industry for the preparation of pure isomers of synthetically prepared drugs. For example, lactate dehydrogenase from Bacillus stearothermophilus has been engineered to accept substrates with a long branched side chain, without loss of its stereospecificity (the native enzyme reduces pyruvate to L-lactate). 

While tremendous advances have been made in asymmetric synthesis, either substrate driven or catalytically induced, resolution of racemates is still the most important industrial approach to the synthesis of enantiomerically pure compounds. Indeed, the resolution of stereoisomers has always been a reliable... 

Matson, S.L (1989) Method for resolution of stereoisomers in multiphase and extractive membrane reactors. US Patent 4,800,162. 

Without additional reagents Resolution of stereoisomers via salts... 

---