Threonine stereoisomers

Threonine, stereoisomers of, 302-303 structure and properties of, 1019 Threose. configuration of, 982 molecular model of, 294 Thromboxane B2. structure of,... 

All of the threonine stereoisomers 19-22 are chiral substances that is, they are not identical with their mirror images. However, it is important to recognize that not all diastereomers are chiral. To illustrate this point, we return to the tartaric acids mentioned previously in connection with Pasteur s discoveries (Section 5-1C). 

The four threonine stereoisomers can be grouped into two paii of enan-tieni The- 2R,3/1 stereoiaomer ts the mirror image of 2S.3S, and the ZRM ateteoisomer is the mirror image of 2S.3K. But what is the rclatioiuhip... 

Diaatereoniera are stereoisomers that are not mirror images of each other Chiral diastereomers have opposite oonfiguralioits at some (one or more) chirality centers, but have the same configuration at others. Enantiomers. by contrast, have opposite configurations at oU chirality centers. A full descriptMHi of the four threonine stereoisomers is given in Table 9.2-... 

FIGURE 4.14 The stereoisomers of isoleucine and threonine. The structures at the far left are the naturally occurring isomers. 

Molecules like lactic acid, alanine, and glyceraldehyde are relatively simple because each has only one chirality center and only two stereoisomers. The situation becomes more complex, however, with molecules that have more than one chirality center. As a general rule, a molecule with n chirality centers can have up to 2n stereoisomers (although it may have fewer, as we ll see shortly). Take the amino acid threonine (2-amino-3-hydroxybutanoic acid), for example. Since threonine has two chirality centers (C2 and C3), there are four possible stereoisomers, as shown in Figure 9.10. Check for yourself that the R,S configurations are correct. 

Table 9.2 I Relationships among the Four Stereoisomers of Threonine...

Threonine (Thr or T) ((2S,31( )-2-amino-3-hydroxybutanoic acid) has an aliphatic hydroxyl side chain and is classified as a polar, uncharged amino acid with the formula HOOCCH(NH2)CHOHCH3. Together with Ser and Tyr, Thr is one of the three proteinogenic amino acids bearing an alcohol group. Thr can be seen as a hydroxylated version of Val. With two chiral centers, Thr can exist in four possible stereoisomers, or two possible diastereomers of L-Thr. However, the name L-Thr is used for one single enantiomer, (2S, 3if)-2-amino-3-hydroxybutanoic acid. The second diastereomer (2S,3S), which is rarely present in nature, is called L- //o-Thr. 

Stereoisomers with more than one chiral center and which are not mirror images of each other hence, stereoisomers that are not enantiomers of each other. For example, L-threonine and D-threonine are an enantiomeric pair whereas L-threonine and D-allothreonine are a diastereomeric pair (as is L-threonine and L-allothreo-nine). Diastereomers will have similar physical, chemical, and spectral properties but those properties will not be identical. If n is the number of chiral centers, then the maximum number of stereoisomers will be equal to 2. However, the actual number for a given set of isomers may be less than 2 due to the presence of meso forms. See Enantiomer Epimer Meso Form... 

The synthesis of four out of eight possible stereoisomers of 3-methyllanthionine [(25,35,67 ), (25,37 ,67 ), (25,35,65), (25,37 ,65)] has been achieved using the reaction of Z-protected 3-methyl-D-cysteine with d- or L-3-chloroalanine in yields of 35—53% J64 The methyl-D-cys-teine stereoisomers were obtained by two routes. Firstly from (25,35)-threonine via O-tosylation and subsequent inversion of configuration by nucleophilic attack with thiobenzoic acid. The resulting derivative was debenzoylated and oxidized to the respective cystine derivative prior to the reduction with Zn/HCl to give the eryt/u-o-3-methyl-D-cysteine... 

Problem 21.17 Threonine has two chiral C s. Write Fischer projections for its stereoisomers. 

We have seen examples of molecules with one chiral center that exist in two mirror-image configurations, which we call enantiomers. What happens when there is more than one chiral center How many stereoisomers should we expect Consider the stereoisomers of the important amino acid, threonine, (2-amino-3-hydroxybutanoic acid). For this substance, if we write all of the possible configurations of its two chiral carbons, we have four different projection formulas, 19-22, corresponding to four different stereoisomers ... 

Reported Physical Properties of the Stereoisomers of Threonine, 2-Amino-3-hydroxybutanoic Acid... 

The description of ci-amino acids as D or L is a holdover from an older nomenclature system. In this system (5)-alanine is called L-alanine. The enantiomer would be D- or ( )-serine. The l (laevo, turned to the left D = dextro, turned to the right) designation refers to the ct-carbon in the essential amino acids. In alanine, there is a single a-carbon that is asymmetric. When two asymmetric centers are present as in L-threonine, the stereochemistry of both carbons must be considered. The common form of L-threonine is the 25,3R stereoisomer. 

The (2S, 3R) stereoisomer is the non-superimposable mirror image of the (2R, 3S) stereoisomer and so these structures are also enantiomers having the same chemical and physical properties. Each set of enantiomers is called a diastereomer. Diastereomer are not mirror images of each other and are completely different compounds with different physical and chemical properties. Thus, threonine has two asymmetric centres, i.e. there are two possible diastereomers consisting of two enantiomers each, making a total of four stereoisomers. As the number of asymmetric centres increases, the number of possible stereoisomers and diastereomers increases. For a molecule having n asymmetric centres, the number of possible stereoisomers is 2" and the number of diastereomers is 2n J. 

Isoleucine and threonine contain an additional stereogenic center at the P carbon, so there are four possible stereoisomers, only one of which is naturally occurring. 

As discussed above, altering the stereochemistry of the sphingosine backbone has produced, in many instances, stereoisomers with altered bioactivity compared with the natural stereoisomer, for example, in activating the catalytic subunit of serine-threonine protein phosphatase 2A (63) or in inhibiting mitochondrial ceramidase (69). 

Look at the amino acid threonine (2-amino-3-hydroxybutanoic acid), for example. Since threonine has two chirality centers (C2 and C3), there are four possible stereoisomers, as shown in Figure 9.10, Check for yourself that the B,S configurations are correct as indicated. 

Of the four stereoisomers of threonine, only the 2S,3R isomer, [alo = -29.3 , occurs naturally in plants and animals. This result is typical Most biologically important molecules are chiral, and usually only a single j stereoisomer is found in nature. 

In this context, it is fascinating that 18 of the natural amino acids crystallize as racemates in a ratio of 1 1, except for threonine and arginine that crystallize as pure d- and pure L-crystals. Serine is particularly unusual as it is formed with an ee of 99% starting from an initial racemate in aqueous solution (Klussmann et al. 2006). Putting the data into perspective, one may conclude that it was likely that meteoritic impact delivered defined molecules from space to Earth. Among them, stereoisomers of a-methyl amino acids were in ee. These optically active compounds were the starting material for the transfer of chirality to other biomolecules. This... 

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