Isoleucine chiral centers

Assign R,S configuration to each chirality center in the following molecular model of the amino acid isoleucine (blue = N) ... 

Isoleucine and threonine (Problem 26.3) are the only two amino acids with two chirality centers. Assign R or 5 configuration to the methyl-bearing carbon atom of isoleucine. 

Isoleucine (He or I) ((25,35)-2-amino-3-methylpentanoic acid) is a nonpolar, neutral, aliphatic amino acid with the formula HOOCCH(NH2)CH(CH3)CH2CH3. Having a hydrocarbon side chain. He is classified as a hydrophobic amino acid. Together with Thr, He is one of the two common amino acids that have a chiral center. Although four stereoisomers of He are possible. He present in nature exists in only one enantiomeric form, that is, (25,35)-2-amino-3-methylpentanoic acid. ... 

Isoleucine is a constitutional isomer of leucine. Note that isoleucine has two chiral centers. 

Diastereoisomers. Whereas compounds with one chiral center exist as an enantiomorphic pair, molecules with two or more chiral centers also exist as diastereoisomers (diastereomers). These are pairs of isomers with an opposite configuration at one or more of the chiral centers, but which are not complete mirror images of each other. An example is L-threonine which has the 2S, 3R configuration. The diastereoisomer with the 2S, 3S configuration is known as i-a//o-threonine. L-isoleucine, whose side chain is -CH(CH3) CH2CH3, has the 2S, 3R configuration. It can be called 2(S)-amino-3(R)-methyl-valeric acid but the simpler name L-isoleucine implies the correct configuration at both chiral centers. 

A novel technique for dating archaeological samples called amino acid racemiza-tion (AAR) is based on the stereochemistry of amino acids. Over time, the configuration at the a-carbon atom of a protein s amino acids is lost in a reaction that follows first-order kinetics. When the a carbon is the only chirality center, this process corresponds to racemization. For an amino acid with two chirality centers, changing the configuration of the a carbon from L to D gives a diastereomer. In the case of isoleucine, for example, the diastereomer is an amino acid not normally present in proteins, called alloisoleucine. 

The chirality of amino acids stems from the chiral, or asymmetric, center, the a-carbon atom. The a-carbon atom is a chiral center if it is connected to four different substituents. Thus glycine has no chiral center. Two of the amino acids, isoleucine and threonine, possess additional chiral centers because each has one additional asymmetric carbon. You should be able to locate these carbons by simple inspection. 

Several V- IJ<>c-A-MOM-a-am ino acid derivatives undergo a-methylation in 78% to nearly 93% ee with retention of the configuration upon treatment with KHMDS followed by methyl iodide at —78°C. The substituents of the nitrogen are essential for control of the stereochemistry. How much is the stereochemical course of the reaction affected by an additional chiral center at C(3) of substrates a-Alkylation of A -lioc-A-MOM-L-isoleucine derivative 61 and its C(2)-epimer, D-a/fo-isoleucine derivative 62, were investigated (Scheme 3.16). If the chirality at C(2) is completely lost with formation of the enolate, a-methylation of either 61 or 62 should give a mixture of 63 and 64 with an identical diastereomeric composition via common enolate intermediate K. On the other hand, if the chirality of C(2) is memorized in enolate intermediates, 61 and 62 should give products with independent diastereomeric compositions via diastereomeric enolate intermediates. 

The stereochemical course of a-alkylation of both L-isoleucine and D-allo-isoleucine derivatives 61 and 62 is controlled predominantly by the chiral axis in the enolate intermediate, whereas the adjacent chiral center C(3) has little effect. 

Figure 3.8. Amino Acids with Aliphatic Side Chains. The additional chiral center of isoleucine is indicated hy an asterisk.

The events that led to this ee may predate the origin of life on Earth. The Murchison meteorite contains almost all natural amino acids as racemates and, importantly, some additional anomalous amino acids that do not occur on Earth (Cronin and Pizzarello 1997 Pizzarello 2006). Among them are four amino acids that do not carry a proton on the asymmetric a-carbon atom but a methyl group. Among the four unnatural amino acids that carry a-methyl substituents is L-a-methyl-aUo-isoleucine. The systematic chemical name of the latter is 2-amino-2.3.-dimethyl-penta-carbonic acid, and it has two chiral centers. Therefore, it should... 

Isoleucine and threonine both have two chiral centers. According to official nomenclature the names L-isoleucine and L-threonine both designate only one optically active diastereoisomer. The mirror images are named D-isoleucine and o-threonine, whereas the diastereoisomers are named l-and D-alloisoleucine and l- and D-allothreonine. The configurations of L-isoleucine and L-threonine are shown in the formulas in Table I. The table also contains notation of the configuration at the two centers according to the R,S system and according to traditional nomenclature for amino acids (lUPAC-IUB, 1975). 

With the exception of glycine all amino acids which are constituents of proteins rotate the plane of polarized light. They are optically active because their a-carbon atom is a chiral center. All have the l, or according to a more contemporary designation the S-configuration, a notable exception being (R)-cysteine (see below). Two amino acids, threonine and isoleucine contain a second chirality center located in their side chains. As indicated in Table 1 the configurations are R in Thr and S in He. 

Isoleucine and threonine contain a second chiral center. Four stereoisomers are possible for each amino acid, but only one is found in proteins. 

Isoleucine and threonine contain a second chiral center. 

Draw all stereoisomers of L-isoleucine. In each stereoisomer, assign the configuration (R or S) of all chirality centers. 

D-hydroxyphenylglycine, L-hydroxyproKne, L-isoleucine, L-lysine, L-ornithine, L-phenylalanine, o-phenylglycine, L-polylysine, L-proline, L-serine, L-threonine, L-tryptophan, and L-tyrosine) was investigated and successfully manufactured on an industrial scale. Glycine is produced by chemical methods because the molecule has no chiral center, and methionine is also produced by chemical methods in its racemic form because the main use of the amino acid is as feedstuff. o-Methionine is metabolized in animals by the action of D-amino acid oxidase. These amino acids were useful as sources of medicines, food additives, feed-stuffs, and starting materials for chemical synthesis. 

Isoleucine has two chirality centers, so we expect four possible stereoisomers, shown here. The configuration of each chirality center is shown. 

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