Biological molecules stereoisomers

Note carefully the difference between enantiomers and diastereomers. Enantiomers have opposite configurations at all chirality centers, whereas diastereomers have opposite configurations at some (one or more) chirality centers but the same configuration at others. A full description of the four stereoisomers of threonine is given in Table 9.2. Of the four, only the 2S,3R isomer, [o]D= -28.3, occurs naturally in plants and animals and is an essential human nutrient. This result is typical most biological molecules are chiral, and usually only one stereoisomer is found in nature. 

Configurational centres impose a rigid shape on sections of the molecule in which they occur. However, their presence gives rise to geometric and optical isomerism. Since these stereoisomers have different shapes, biologically active stereoisomers will often exhibit differences in their potencies and/or activities (Table 2.1). These pharmacological variations are particularly likely when a chiral centre is located in a critical position in the structure of the molecule. The consequence of these differences is that it is now necessary to make and test separately all the individual stereoisomers of a drug. 

Problem 19.62. Cholesterol is one of many stereoisomers, another example of the great stereoselectivity of biological molecules. Place an asterisk next to each stereocenter in cholesterol and indicate the total number of stereoisomers. 

Perhaps the most conspicuous examples of chirality among biological molecules are the enzymes, all of which have many stereocenters. An example is chymotrypsin, an enzyme found in the intestines of animals. This enzyme catalyzes the digestion of proteins (Section 19.5). Chymotrypsin has 251 stereocenters. The maximum number of stereoisomers possible is... 

Stereoisomers have the same order of attachment of the atoms, but different arrangements of the atoms in space. The differences between stereoisomers are more subtle than those between structural Isomers. Yet stereoisomerism is responsible for significant differences in chemical properties of molecules. The effectiveness of a drug often depends on which stereoisomer is used, as does the presence or absence of side effects (see A Word About.. . Enantiomers and Biological Activity," pp. 1 72-1 73). The chemistry of life itself is affected by the natural predominance of particular stereoisomers in biological molecules such as carbohydrates (Chapter 1 6), amino acids (Chapter 17), and nucleic acids (Chapter 18). 

The 1,2-dimethylcyclopropanes are members of a subclass of stereoisomers called cis-trans isomers. The prefixes cis- (Latin, on the same side ) and trans- (Latin, across ) are used to distinguish between them. Cis-trans isomerism is a common occurrence in substituted cycloalkanes and in many cyclic biological molecules. 

The structure of biotin was determined in the early 1940s by Kogl in Europe and by dn Vigneand and coworkers in the United States. Interestingly, the biotin molecule contains three asymmetric carbon atoms, and biotin could thus exist as eight different stereoisomers. Only one of these shows biological activity. 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Enantiomers are characterized as nonsuperimposable mirror images. Enantiomers are said to be chiral (note that some diastereomers may be chiral as well). In the context of the same bonding pattern or connectivity, which atoms are bonded to which, enantiomers have handedness and are related to each other as the right hand is related to the left hand. In the specific example we saw earlier, the carbon atom is linked to four different atoms. Such molecules have non-superimposable mirror images. Stereoisomerism occurs in some molecules that do not have such a carbon atom but these cases are more exotic than we need to worry about here. Stereoisomers frequently have different, and sometimes strikingly different, biological properties, exemplified by the thalidomide case. 

The non-identical compounds include ones that have the same chemical structure and formula as ones found in nature, but which are not the same stereoisomer the molecule (or part of it) is asymmetric, so can take two spatial forms which are mirror images of each other. Often only one of these forms is made by natural systems, but both are made by industrial synthesis. The biological effects of the two forms may be quite different (see RCEP, 2003, ppl 3—14). 

Nearly all biological compounds with a chiral center occur naturally in only one stereoisomeric form, either d or L. The amino acid residues in protein molecules are exclusively L stereoisomers. D-Amino acid residues have been found only in a few, generally small peptides, including some peptides of bacterial cell walls and certain peptide antibiotics. 

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