Suppliers chiral compounds

Majors, such as DSM and Kaneka, have often developed a technology base from experience gained in making, for example, antibiotic side chains and angiotensinconverting enzyme (ACE) inhibitor intermediates. For most major suppliers, chiral compounds are only a part of their overall activity. 

Obviously, in a relatively small work such as this it is not possible to be comprehensive. Preparations of bulk, achiral materials (e.g. simple oxiranes such as ethylene oxide) involving key catalytic processes will not be featured. Only a handful of representative examples of preparations of optically inactive compounds will be given, since the emphasis in the main body of this book, i.e. the experimental section, is on the preparation of chiral compounds. The focus on the preparation of compounds in single enantiomer form reflects the much increased importance of these compounds in the fine chemical industry (e.g. for pharmaceuticals, agrichemicals, fragrances, flavours and the suppliers of intermediates for these products). 

In the search for unique properties, chemists have isolated pertinent compounds, for which they have revealed the structures and in many cases developed syntheses. For many, in general, simpler compounds, industrially feasible preparations have also been worked out. However, for most of the more complex structures, nature proves to be much more efficient and cheaper, especially in the field of chiral compounds. Therefore, nature is still the supplier of many natural products, which are useful as such or as starting materials for other chemicals and auxiliaries in new chemical reactions. 

CCCs may be companies that specialize in chiral compounds, such as Celgene, Chiroscience, and Oxford Asymmetry, or may have developed into a chiral raw material supplier to an industry other than its original main customer base [e.g., Takasago, a flavor manufacturer, who developed a catalytic route to (-)-menthol, and used related technology to make beta-lactam intermediates]. 

Medium and minor players will typically have an exploitable intellectual property base from which they are developing or seeking to establish themselves chiral compounds are often the only products offered. However, as potential commercial suppliers at scale, they will be dependent on subcontracted production, including alliances with larger companies with available production capacity or significant capital investment. Examples are Synthon Corporation, which makes C4 synthons from carbohydrate raw materials, and Oxford Asymmetry, which exploits S. Davies work and patents and is in alliance with Cambrex. Customers will need to assess the adequacy of financial arrangements and/or the suitability of the chosen production partner. 

Understanding the technology potentially applicable to the required chiral compound is important, as is knowledge of suppliers particular areas of strength and... 

Of course, this is not to say that costs should not be minimized and potential complications, such as impurity profiles, etc., avoided by working with potentially commercial sources as early in the development process as possible. The problem is that only approximately 10% of phase I candidates will eventually be launched, and, furthermore, estimates of ultimate commercial demand will usually only become available toward the end of phase II. Suppliers may incur significant development costs before having any idea of the potential return, if, indeed, there is to be one at all. Obviously, this situation is not unique to chiral compounds and has lead to customers working with a selected number of preferred suppliers who gain access to a continuing number of opportunities. Speed of response will be one very important factor in making this selection. 

The suppliers of fine chemicals initially produce many new chiral compounds in kilogram amounts on the assumption that scale-up to an annual production of about 1 tonne is practical. The pharmaceutical industry almost certainly produces other synthons on this scale from its own resources. The outcome is likely to be an increasing use of enzymes in... 

Enantiomeric purity. In order to assess the efficiency of an enantioselective hydrolase-catalyzed reaction, it is imperative that one can accurately measure at least the conversion and the enantiomeric excesses of either the substrate or the product (see equations Equation 1, Equation 2, and Equation 3). Although optical rotation is sometimes used to assess enantiomeric excess, it is not recommended. Much better alternatives are various chromatographic methods. For volatile compounds, capillary gas chromatography on a chiral liquid phase is probably the most convenient method. Numerous commercial suppliers offer a large variety of columns with different chiral liquid phases. Hence it is often easy to find suitable conditions for enantioselective GC-separations that yield ee-values in excess of... 

In the course of the development of CSPs, a broad variety of chiral molecules (and materials) has been the subject of scrutiny with respect to chromatographic enantiomer separation capacity. The chiral molecules studied as potential SOs cover virtually the entire chemical and structural diversity space, ranging from low-molecular-weight compounds to polymers of both synthetic and biological origin. So far, the (stiU ongoing) quest for efficient SOs has resulted in the synthesis of more than 1400 CSPs [94], the properties of which are documented in an almost intractable number of dedicated scientific publications. The outcome of these efforts is manifest in an enormously rich toolbox of more than 200 commercially available CSPs offered by various speciahzed suppliers. 

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