D-allo-isoleucine

D-Allo-isoleucine and L-isoleucine derivatives have been prepared from the corresponding mixture of stereoisomers via a diastereoselective hydrolysis reaction catalyzed by the enzyme alcalase (Scheme 2.6). Initially, enantiomerically and diastereomerically pure derivatives of L-isoleucine 10 were submitted to chemical epimerization to yield a 1 1 mixture of stereoisomers at the a-position. Thereafter,... 

Scheme 2.6 Preparation of D-allo-isoleucine 13 from L-isoleucine.

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. 

This activation was successfully used in the preparation of unusual Y-amino-p-hydroxy esters such as the protected derivative of (354R5S)- Isostatine from D-allo-isoleucine as shown in scheme 212 (Ref. 262). 

At equilibrium, the concentration of alloisoleucine does not equal that of isoleucine (58). The rate expression for Equation 13 is similar to that given in Equation 9 except k (D-amino acid) is replaced by k (D-allo-isoleucine). Since the solutions initially contained only L-isoleucine, when the amount of racemization is small, the term k (D-alloisoleu-cine) can be neglected in the rate expression and in this case the integrated rate equation is... 

Almost all actinomycins have the same chromophore, a planar phenoxazinone dicarboxylic acid called actinociiL In dactinomycin, the structure of which is shown in Figure 12, the two pendent pentapeptide lactones are identical, but in other actinomycins these lactones may be different. In other actinomycins the first amino acid, amide linked with actinocin, is usually L-threonine, as in dactinomycin the second position is sometimes D-allo-isoleucine instead of D-valine the third position may be sarcosine or oxoproline the fourth position is sarcosine and the fifth position is sometimes iV-methyl isoleucine instead of N-methylvaline. The lactone ring is always present. 

Sporidesmolides cyclic depsipeptides om the fungus Pithomyces charumtm. Sporidesmolide I is c -clo-(-Hyv-D-Val-D-Leu-Hyv-Val-MeLeu-) sporidesmolide II contains D-allo-isoleucine in place of D-va-line, while sporidesmolide III contains L-leucine in place of L-Al-methylleucine. (Hyv represents a residue of a-hydroxyisovaleric acid). 

L-Isoleucine (2S 3S)-Isoleucine (Common in proteins) D-Isoleucine (2R 3R)- Isoleucine L-allo- D-allo Isoleucine Isoleucine (2S 3R)- 12R 3S)-Isoleucine Isoleucine (1.8) ... 

Chloro HPIA chloro-p-hydroxyphenyUactic acid D-allo-l e D-allo-isoleucine Choi sulfate 2-carboxy-6-hydroxy-octahydroindole sulfate Agma agmatine 98 means that it is strain 98 of NIES, National Institute for Environmental Studies, inTsukuba, Japan). 

Among the amino acids, threonine, hydroxylysine, cystine, isoleucine, the two hydroxyprolines, and others possess two optically active centers. Therefore, the synthetic compounds are mixtures of four diastereoisomers the l- and d- forms, and the L-allo- and D-allo- forms, respectively. For example, threonine can have these four forms L-threonine (XLI), D-threonine (XLII), L-allothreonine (XLIII), and D-allothreonine (XLIV). 

Synthesis. Dn-Isoleucine is synthesized in about 27% over-all yield by the method of Marvel (554). Diethyl sec.-butylmalonate (A) is prepared in 83% yield from diethyl malonate, sodium, absolute ethanol and sec.-butyl bromide (b.p. 91.3°C.) essentially by the method of Romburgb (673). a-Bromo- S-methylvaleric acid (B) is pr ared in about 67% yield by the alkaline hydrolysis of (A), isolation of sec.-butylmalonic acid ((j), and bromination and decarboxylation of (C). DL-Isoleucine (D), prepared by amination of (B), is recrystallized from 30% ethanol. It has been suggested (39, 485) that the product should be repeated recrystallized from 80% ethanol to free it from allo-isoleucine. It has been found in the writers laboratory that recrystallization from 20% ethanol is an effective purification procedure. The described s thesis is essentially that originated by Brasch and Friedman (125) and Ehrlich (237) and employed by Abd halden and Zeisset (39). 

Isoleucine, threonine, 4-hydroxyproline and 3-hydroxyproline also have an asymmetric carbon atom in the side chain (two chiral centres in total). They can therefore occur in four stereoisomeric forms (this number is equal to 2 = 2 = 4, where = number of asymmetric carbon atoms) known as l-, d-, L-allo- and d-allo- according to the configuration of the carbon carrying the amino group. The unique RIS system is not widely used in biochemistry. The stereoisomers of isoleudne are thus called L-isoleucine or (2S,3S)-isoleucine (2-4), D-isoleucine or (2R,3R)-isoleucine (2-77), L-a//o-isoleudne or (2S,3R)-isoleudne (2-78) and D-fl//o-isoleucine or (2fi,3S)-isoleucine (2-79). Proteins contain only L-isoleudne. The product of enzymatic or thermal isomerisation of L-isoleucine is D-oZZo-isoleudne. Likewise, proteins contain L-threonine or (2S,3R)-threonine (2-4) and L-4-hydroxyproline or (2S,4S)-4-hydroxyprohne (2-6). Cystine (as well as lanthionine, see Sedion 2.5.1.3.4) contains two identical asymmetric carbons in the molecule and, therefore, only exists in three different isomers. Proteins contain just L-cystine (2-4), its isomer is D-cystine (2-80) and the mesoform meso-cystine (2-81) is a symmetrical molecule. 

Conventional processing of food raw materials, as well as culinary methods used during food preparation, does not usually cause a significant isomerisation (racemisation) of L-amino acids (Table 2.25) (with the exception of aspartic acid), l-Aspartic acid and L-serine undergo racemisation relatively easily. L-lsoleucine (isomerises to D-flHo-isoleucine), L-prohne, L-threonine (isomerises to D-allo-threonine) and L-vahne yield smaller amounts of o-isomers. Free amino acids are roughly ten times more stable than amino acids bound in proteins. An extensive racemisation of amino acids does however occur, even at relatively low temperatures, in alkaline media used to inactivate enzymes, microorganisms, microbial... 

D-isoleucine, allo-D-isoleucine, A-methyl-L-isoleucine iV-methyl-L-leucine, / -JV-dimethyl-L-leucine, n- 3-hydroxyleucine, D-leucine L-/S-lysine... 

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