Isoleucine configurations

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. 

Chemical structure. The structure of the free base of Cypridina luciferin (C22H27ON7, Mr 405.50) was determined by Kishi et al. (1966a,b) as shown below (A) its sec-butyl group is in the same configuration as in L-isoleucine. The structure of oxyluciferin reported by the same authors contained an error, and the structure was corrected later as shown in Fig. 3.1.8 (McCapra and Chang, 1967 Stone, 1968). 

S)-leucine, and (S)-sec-butyl-(R)-oxirane from (2S,3S)-isoleucine, respectively. This useful three-step route complements the synthesis of (S)-alkyloxiranes from (S)-2-araino acids via (S)-2-hydroxy acids,with retention of configuration at the stereocenter. 

From the analytical point of view, it is worth noting the biogenetic pathway of 2-methylbutanoic acid starting from isoleucine [(2S)-amino-(3S)-methylpenta-noic acid]. The (S)-configuration of the precursor is expected to remain but also enzymatic racemisation (by enolisation of the intermediate 2-oxo-3-meth-ylpentanoic acid) is known from the literature. It is not surprising that in some cases 2-methylbutanoic acid is detected as an enantiomeric ratio more or less different from the expected homochiral S enantiomer (Table 17.2) [35-40]. 

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. 

Isoenzymes (isozymes) 536, 538 Isoionic point 106 Isolation of compounds 98-108 Isoleucine (He, I) 52s, 539 biosynthesis 540 branched fatty acids from 381 configuration 43 Isologous interactions 337-353 in oligomers 349 - 353 square 352s... 

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. 

While enantiomerically pure a-substituted isocyanoacetates have been used in Passerini condensation without significant racemization [4-6], the same class of compounds is believed to be configurationally unstable under the conditions of U-4CRs [7]. However, one notable exception is the reaction shown in Scheme 1.1, where L-isoleucine-derived isocyanide 2 has been condensed without such problems with pyrroline 1 [8]. The bulkiness of this isocyanide or the use of a preformed cyclic imine, thus avoiding the presence of free amine in solution, may be the reasons for the absence of racemization. 

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 edulinic acid residue found in K17 and K19 may share a similar bio-genetic origin to evoninic acid. Both may be viewed as products of coupling of (at a different oxidation level) nicotinic acid (or quinolinic acid) at C-2 with C-4 or C-5 of isoleucine as in 63. The absolute configuration at C-3 of isoleucine is the same as at C-8 of evoninic acid, but that of edulinic acid is not yet known. 

Trommel, J., and Bijvoet, J. M. Crystal structure and absolute configuration of the hydrochloride and hydrobromide of D(-)-isoleucine. Acta Cryst. 7, 703-709 (1954). 

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