Metal enolates pharmaceuticals

Mannich and related readions provide one of the most fundamental and useful methods for the synthesis of p-amino carbonyl compounds, which constitute various pharmaceuticals, natural products, and versatile synthetic intermediates.1271 Conventional protocols for three-component Mannich-type readions of aldehydes, amines, and ketones in organic solvents indude some severe side reactions and have some substrate limitations, espedally for enolizable aliphatic aldehydes. The dired synthesis of P-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view. Our working hypothesis was that aldehydes could read with amines in a hydro-phobic reaction fidd created in water in the presence of a catalytic amount of a metal triflate and a surfactant to produce imines, which could then read with hydrophobic silyl enolates. 

The asymmetric aldol reaction is one of the most important topics in modern catalytic synthesis [54]. The products, namely />-hydroxy carbonyl compounds, have a broad range of applications and play a key role in the production of pharmaceuticals [55], Since the discovery of the catalytic asymmetric aldol reaction with enolsi-lanes by Mukaiyama et al. [56], steady improvements of the metal-catalyzed asymmetric aldol reaction have been made by many groups [57]. For this type of aldol reaction a series of chiral metal catalysts which act as Lewis acids activating the aldol acceptor have been shown to be quite efficient. It was recently shown by the Shibasaki group that the asymmetric metal-catalyzed aldol reaction can be also performed with unmodified ketones [57a], During the last few years, several new concepts have been developed which are based on use of organocatalysts [58], Enolates and unmodified ketones can be used as aldol donors. 

B. Enol-containing Biochemicals and Pharmaceuticals and Their Metal... 

The carbonyl functionality is one of the most abundant functional groups in biomolecules and pharmaceuticals, including many a- and /3-carbonyl derivatives of ketones and aldehydes and their enol tautomers, which upon deprotonation can form entropy-favored 5-membered (37) and 6-membered (38) chelates with metal ions. In this section, the role of metal ions in the action of some enol-containing biochemicals and pharmaceuticals and the structures of their metal complexes are discussed. 

The electrochemical detector is extremely sensitive, but suffers from two main drawbacks. Firstly, the mobile ( ase has to be extremely pure, in particular, free of oxygen and metal ions. Secondly, by-products of the oxidation or reduction processes are often absorbed on the surface of the electrodes and thus, if quantitative activity is required, frequent calibration is necessary. Ultimately the electrodes have to be cleaned usually by mechanical abrasion and replaced in the cell. Electrochemical detection is particularly suitable for small bore columns and possibly, in the future, LC capillary columns, due to the fact that the detector can be made extremely small in size. The detector has had a fairly wide area of application. It has been used under oxidizing conditions for the detection of phenols, hydroquinone and catechols and in particular for many compounds of biological interest including, catecholamines (35). It has been used to determine substances of industrial interest, and agricultural chemicals (36). In its oxidation form, it has been used to detect amines of various types together with i enols and thiols. It has also been used in the analysis of ascorbic acid in food and biological materials, and in the pharmaceutical industry, for the analysis of multivitamin products. 

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