NSC Technologies

A Rh-dipamp complex was later applied by NSC Technologies for the manufacture of several unnatural amino acids with good catalyst performances (ee 95-98%, TON 5000-20000) [30] and was also very selective but with low activity (ee 98%, TON 20) in a feasibility study for a synthesis of acromelobic acid by Abbott Laboratories [31]. 

Great Lakes Fine Chemicals Know-how from NSC Technologies/Monsanto, several production and pilot processes [30]. 

Asymmetric hydrogenation of proprietary P-keto esters with [RuCl2(BINAP)]n in 98-99% ee had been performed by NSC Technologies (Scheme 12.13). Substrate-to-catalyst loadings of 10,000-20,000 have been achieved. These reductions have been performed at small-scale production to ton scale.23 Phoenix Chemicals, whose specialty is in continuous processes, has developed methodology and equipment that can perform this type of transformation up to -100 tons/year for a proprietary P-hydro ester with enantioselectivities of 98-99% ee (see Chapter 31).6768... 

The synthesis of chiral a-amino acids starting from a-keto acids by means of a transamination has been reported by NSC Technologies [115]. In this process, L-aspartate serves as the amino donor. The substrate specificity is broad, allowing the conversion of numerous keto acid substrates. 

Kaneka, Nippon Soda, Takasago NSC Technologies Yamakawa Yamakawa... 

Among stereospecific chemical methods, asymmetric hydrogenation, hydroformylation, hydrocyanation, and isomerization offer some of the potentially most economic routes. As long as the substrate is relatively accessible and the turnover number is high, low costs are achievable. Development times are usually not unduly excessive. Catalyst availability is becoming less of an issue as some patent holders are now prepared to license out for specific applications. Thus, there is a wider choice of potential sources, such as Bayer, Chiroscience, and NSC Technologies. 

The preferred auxiliaries in chemistry at NSC Technologies are oxazolidinones. Oxazolidinones have found widespread use as chiral auxiliaries. A wide range of reactions is available and well documented [5], including aldol alkylations oc-substitution with a heteroatom such as halogenation, aminations, hydroxyla-tions, and sulphenylations Diels-Alder cycloadditions and conjugate additions. 

Although the asymmetric hydrogenation methodology used at NSC Technologies does not allow access to cyclic amino acid derivatives at present, it is an area that is being researched. To obtain D-proline, we have performed a dynamic resolution with L-proline as the starting material. The presence of butyraldehyde allows racemization of the L-proline in solution, whereas the desired o-isomer is removed as a salt with o-tartaric acid [22,23]. 

David J. Ager, Ph.D. Fellow, NSC Technologies, Mount Prospect, Illinois... 

The synthesis of chiral a-amino acids starting from a-keto acids by means of a transamination has been reported by NSC Technologies [26, 27]. In this process, which can be used for the preparation of l- as well as D-amino acids, an amino group is transferred from an inexpensive amino donor, e.g., L-glutamic acid, l-22, or L-aspartic acid, in the presence of a transaminase (= aminotransferase). This reaction requires a cofactor, most commonly pyridoxal phosphate, which is bound to the transaminase. The substrate specificity is broad, allowing the conversion of numerous keto acid substrates under formation of the L-amino acid products with high enantioselectivities [28]. 

A sales figure makes the importance of this business evident. Pharmaceutical companies spent 3 billion in 1996 to buy large quantities of pharmaceutical intermediate chemicals and bulk actives Stinson, 1997). Ordinarily neither kind of chemical is available from other commercial sources because each represents a new compound. Contractual work provides both kinds of compormds and employs chemists. Several companies specialize in making chiral intermediates on large scales. They include Cat-alytica in California, Degussa in New Jersey, Synthon in Michigan, and NSC Technologies in Illinois, but are not limited to these examples. 

NSC Technologies, A Unit of Monsanto, 601 E. Kensington Road, Mt. Prospect, IL 60056 Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, Ml 48105... 

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