Chiral technology

As mentioned previously, cellulosic phases as well as amylosic phases have also been used extensively for enantiomeric separations more recently (89,90). Most of the work ia this area has been with various derivatives of the native carbohydrate. The enantioresolving abiUties of the derivatized cellulosic and amylosic phases are reported to be very dependent on the types of substituents on the aromatic moieties that are appended onto the native carbohydrate (91). Table 3 fists some of the cellulosic and amylosic derivatives that have been used. These columns are available through Chiral Technologies, Inc. and J. T. Baker, Inc. 

Mobile phases used with this stationary phase are typically 0.01 N perchloric acid with small amounts of methanol or acetonitrile. One significant advantage of these phases is that both configurations of the chiral stationary phase are commercially available and can be obtained from J. T. Baker Inc. and Chiral Technologies, Inc. (Crownpak CR). 

Another type of synthetic polymer-based chiral stationary phase is formed when chiral catalyst are used to initiate the polymerisation. In the case of poly(methyl methacrylate) polymers, introduced by Okamoto, the chiraUty of the polymer arises from the heUcity of the polymer and not from any inherent chirahty of the individual monomeric subunits (109). Columns of this type (eg, Chiralpak OT) are available from Chiral Technologies, Inc., or J. T. Baker Inc. 

The ability to efficiently synthesize enantiomerically enriched materials is of key importance to the pharmaceutical, flavor and fragrance, animal health, agrochemicals, and functional materials industries [1]. An enantiomeric catalytic approach potentially offers a cost-effective and environmentally responsible solution, and the assessment of chiral technologies applied to date shows enantioselective hydrogenation to be one of the most industrially applicable [2]. This is not least due to the ability to systematically modify chiral ligands, within an appropriate catalyst system, to obtain the desired reactivity and selectivity. With respect to this, phosphorus(III)-based ligands have proven to be the most effective. 

Johnson Matthey, Catalysis and Chiral Technologies (Synetix) In licensed chiral ligands, process R D. Metal precursors and M-L complexes in technical quantities recovery of noble metals [112]. 

Chiral cyanohydrins in fact are high-value building blocks and useful precursors for hydroxyamino acids and amino alcohols. The new sol-gel immobilization technology licensed from Johnson Matthey and named CTIS CACHy (CTIS Chiral Technologies Interface System)32 dramatically improves process economics for large-scale pharmaceutical manufacturing as it increases the turnover number of the catalyst... 

CHIRALCEL OD-H is available from Chiral Technologies Inc. The checkers used a 15-cm column, with a 97 3 hexane/2-propanol mixture as eluant, a flow rate of 0.5 mL/min, and detection by Rl detector. The tR of the R-isomer (17.0 min) is shorter than that of the major S-isomer (17.8 min). The submitters used a 25-cm column with a 94 6 mixture of hexane/2-propanol as eluant and a flow rate of 0.5 mL/min. Under the latter conditions, the tR s of the R- and S-isomers are 17.9 min and 19.4 min, respectively. 

FIGURE 1.2 Structure and stereochemistry of commercially available cinchona alkaloid CSPs, marketed under trade name CHIRALPAK by chiral technologies europe. QN denotes quinine- and QD quinidine-derived and AX refers to their anion-exchanger capabilities vide infra). 

Chiral Technologies, Europe, Application note (CTE Flyer) (2005). 

Recently, chiral economic techniques have been developed which allow the complete transformation of a starting material into the desired enantiomer. According to a study by the market research firm of Frost and Sullivan, worldwide revenues due to chiral technology, which amounted to US 4.8 billion in 1999, will have reached more than triple the sum by 2009 — US 14.9 billion. One valuable approach is using the chiral pool as a large reservoir of optically pure building blocks, mainly derived from natural sources. 

Similarly, chiral amines also feature increasingly prominently as intermediates in new pharmaceuticals (Figure 2.2). Compared to amino acids, amines offer a particular challenge in view of the paucity of different available chiral technologies that have been developed to a point where they are of practical utiUty [3]. 

Suven Life Sciences Synthon Chiragenics (Monmouth Junction, NJ, USA) Carbohydrate-based chiral technology N/A... 

This work was carried out by a highly skilled and motivated team of people from all areas of GSK, and 1 would hke to thank aU of them for their commitment and dedication to the project. In addition 1 would like to acknowledge the assistance from the staff of Novasep (France) and Chiral Technologies Europe for their contributions and very helpful discussions to the development of the MCC process. It is to all of these people that this chapter is dedicated. 

Several other synthetic routes also exist. The stereospecific Syntex process is an example using chiral technology to produce enantiomerically pure naproxen ... 

These columns are available ihruugh Chiral Technologies. Inc. and J T. Baker. Inc. 

Crownpak CR Crownpak CR Crownpak CR Opticrown RCA Chiralhyun-CR-1 Chirosil CH RCA Chiral Technologies Inc., Exton, PA, USA Separations Kasunigaseki-Chrome, Tokyo, Japan Daicel Chemical Industries, Tokyo, Japan USmac Corporation, Winnetka, Glenview, USA K-MAC (Korea Materials Analysis Corp.), South Korea Rstech, Corporation, Daedeok, Daejon, South Korea... 

A group at Industrial Research Limited in New Zealand recently reported the results of a study to determine if a cross-linked enzyme crystal-catalyzed resolution can compete with alternative chiral technologies in the pharmaceutical and chemical process industries. The group used the enantioselective hydrolysis of a-phenylethyl acetate catalyzed by ChiroCLEC -PC as a model system (Fig. 13). Based on their results with 270 kg of racemate, they evaluated the economics of mnning the process at the 600-kg batch scale and concluded that this process is economically feasible [38],... 

In this chapter, recent applications of (W)-phcnylglycine amide (1) in asymmetric synthesis are presented (Figure 25.2). The first section deals with diastereoselective Strecker reactions for the preparation of a-amino acids and derivatives, whereas the second section focuses on diastereoselective allylation of imines for preparation of enantiomerically pure homoallylamines. This latter class of compounds is a well-known intermediate for the synthesis of, for example, many types of amines, amino alcohols, and P-amino acids. The final section describes reduction of imines providing enantiomerically pure amines. (S)-3,3-Dimethyl-2-butylamine and (S)-l-aminoindane will be presented as leading examples. The results described in this chapter originate from a longstanding cooperation in the field of chiral technology development between DSM Pharma Chemicals and Syncom B.V. 

Here, we describe several successful examples of the development of chiral technologies using biocatalytic methods. These developments were based on extensive screening of microorganisms, and the consequent discovery of novel enzymes and their functions. 

---