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. 

Thus hydrogenolysis of coronamic acid (505) led to a mixture of isoleucine, allo-isoleucine, norleucine and 2-amino-2-methylvaleric acid this demonstrates, that all... 

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). 

Includes allo-isoleucine, a-NH butyric acid 2-4-diaminobulyric acid, diaminopimelic acid, fi-alanine, ethanolamine, and unidentified compounds. 

The l enantiomers of a- methyl-isoleucine and a-methyl-allo-isoleucine are in fact the four diastereomers of 2-amino-2.3-dimethyl-penta-carbonic acid. The crucial result of the analysis of these a-substituted amino acids showed that their L-enantiomers each had an ee of 12.1.4% and 14.0%, respectively, similar to Murchison s (Pizzarello et al. 2006). 

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. 

A new semisynthetic peptide alkaloid, 9,10-a-dihydro-12 -hydroxy-2 -isopropyl-5 a-(i -l-methylpropyl)ergotaman-3, 6, 18-trione (DCN 203-922), which contains the unnatural amino acid L-allo-isoleucine, was prepared and was found to have affinity to different monoamine binding sites in the brain [57]. 

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). 

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). 

DL-Isoleucine is synthesized in about 56% over-all yield by the method of Hamlin and Hartung (366). o-Oximino- -methyl-w-valeric acid (A) is prepared in 70% yield from ethyl sec.-bulyl acetoacetate, butyl nitrite and sulfuric acid. DL-Isoleucine is prepared in 80% yield by the reduction of (A) with hydrogen, palladium chloride and ethanol. This method is essentially the same as that originated by Bouveault and Locquin (117, 118, 525). By the comparable procedure of Feofilaktov (264, 265) the phenylhydrazone of methyl ethyl pyruvic acid, prepared from sec.-butyl acetoacetate and phenyldiazonium chloride (aniline and NaN02) in 68% yield, is reduced by means of rinc and alcoholic HCl to nearly the theoretical yield of a mixture of DL-isoleucine and DL-allo-isoleucine. Ehrlich (235) synthesized a mixture of isoleucine and allo-isoleucine from 2-methyl-n-butyraldehyde by the Strecker reaction. 

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) ... 

The following system of abbreviations for amino acids will be used Abu = L- <>-aminobutyric acid Ala = L-alaninei /3-Ala = /3-alanine Arg = L-arginine Asn = L-asparagine Asp = L-aspartic acid Cys = L-cysteine (or L-half cystine) Dbu = L-o y-diamino-butyric acid Gin - L-glutamine Glu = L-glutamic acid Gly = glycine His = L-histidine lie = L-isoleucine alle = L-allo-isoleucine Leu = L-leucine Lys = L-lysine ... 

---