Stereochemical biological selectivity

This example illustrates a subtle control of a chemical reaction by a delicate manipulation of tire stereochemical environment around a metal centre dictated by tire selection of tire ligands. This example hints at tire subtlety of nature s catalysts, tire enzymes, which are also typically stereochemically selective. Chiral catalysis is important in biology and in tire manufacture of chemicals to regulate biological functions, i.e., phannaceuticals. 

The biological properties of phosphorus amino acid analogues (and their derivatives) depend upon their stereochemistry. Consequently, numerous methods for obtaining these compounds in stereochemically pure form have been developed. Two excellent review articles summarize the work performed prior to 1993. 3,4 Resolution of racemates continues to be a useful approach for obtaining optically pure aminoalkylphosphonic and -phosphinic acid derivatives (vide infra), but most of the newer literature describes asymmetric syntheses of these compounds.15-17 Two methods for resolution and one for asymmetric synthesis are described (vide infra) they have been selected since they are relatively easy to perform, work with a variety of side chains, can be carried out on a reasonable scale with readily available starting materials, and produce products of high stereopurity. However, just as in traditional amino acid chemistry, each side chain introduces its own complications, and in many cases, especially for more complex analogues, other methods may be preferred. 

A recent screening of various chiral carboxylic acids has allowed the selection of galacturonic derivative 12 as a very efficient control in the stereochemical course of some Passerini reactions (Scheme 1.5). Although the de seems to be strongly dependent on the isocyanide employed, this result suggests the possibility of employing carboxylic acids as easily removable chiral auxiliaries in the asymmetric synthesis of biologically important mandelamides [16]. 

Stereochemistry is the study of the three-dimensional structure of molecules. No one can understand organic chemistry, biochemistry, or biology without using stereochemistry. Biological systems are exquisitely selective, and they often discriminate between molecules with subtle stereochemical differences. We have seen (Section 2-8) that isomers are grouped into two broad classes constitutional isomers and stereoisomers. Constitutional isomers (structural isomers) differ in their bonding sequence their atoms are connected differently. Stereoisomers have the same bonding sequence, but they differ in the orientation of their atoms in space. 

The transformation is only moderately stereoselective in this situation and the stereochemical outcome of the reaction is explained by a complexation of the samarium atom by the acetamido group in the kinetic a-Sm(IIl) species 186, slowing down the isomerization to the /3-species. The anomeric selectivity is completely lost when operating with the acetylated sulfone 187. A solution to restore a selective reaction and to access to C-glycosides mimicking the biologically ubiquitous /3-GlcNAc motif, relies on this intermolecular samarium-Barbier reaction followed by an oxidation-isomerization sequence [91] (O Scheme 39). 

The widespread occurrence and biological significance of the macrolide ansamycin and polyether antibiotics, and of polyhydroxylated natural products, including rare carbohydrates, among others, has stimulated considerable interest in the development of concise, efficient synthetic methodology for the stereo-and enantio-selective construction of stereochemically adorned acyclic molecules.Indeed, considerable effort has been devoted towards the development of highly stereoselective syntheses of the so-called propionate (e.g.—CHMe—CHOH—CHMe—CHOH—), acetate (c.g.—CHOH—CH2CHOH—CH —)... 

In some respects achieving the product specificities is the most important goal. Substrate specificity is critical in the soup of components found in a biological cell, but chemical reactions can usually be performed on pure substrates where substrate specificity of a catalyst is irrelevant. However, the ability of an enzyme to achieve selective reactions on a particular section of the substrate (regioselectivity) and with specific stereochemical consequences (stereoselectivity) are features to be admired and imitated in chemical systems. 

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