Hydroxy leucine

The highly oxygenated ergosterol derivatives, ergokonin A and B (165, 166), are produced by T. koningii and T. viride isolates [232]. Ergokonin A is characterised by esterification at the 3-hydroxyl with the unusual 3-hydroxy-leucine-3-O-sulphate moiety [231] and has been shown cause... 

Fowden et al. (1973) isolated 4-hydroxy leucine from the seeds of fenugreek. Later, Alcock et al. (1989) determined its absolute configuration as (2S, 3R, 4S). From the leaves and stems, y-schizandrin and scopo-letin (7-hydroxy-6-methoxycoumarin) were isolated by Wang et al. (1997). Shang et al. 

Fowden, F., Pratt, H.M. and Smith, A. (1973) 4-Hydroxy leucine from seed of Trigonella foenum graecum. Phytochemistry 12, 1707-1 711. 

Leucine oxidized with "OH produces a 5 -hydroperoxy derivative which is subjected to chemical reduction to yield (2S)-y-hydroxyleucine, (2S,4S)-8-hydroxy-leucine, (2S,4R)-8-hydroxyleucine. The S -hydroxyleucines have been confirmed to be the reduction products of the corresponding hydroperoxyleucines. 5 -Hydro-xylysines are natural products formed by lysyl oxidase and therefore are not useful markers of radical-mediated oxidation. The other hydroxylysines are useful markers, however, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC)... 

An aq. soln. of glycine, ca. 0.05 mole of cupric sulfate, and 4 moles of Na-carbonate treated with ca. 8 moles of isobutyraldehyde, refluxed 30 hrs. with efficient stirring, more aldehyde added, and refluxing continued ca. 0.5 hr. until most of the blue color of the cupric ions is discharged -hydroxy-leucine. Y 67%. F. e. s. T. T. Otani and M. Winitz, Arch. Biochem. Biophys. 102, 464 (1963) with the amino acid Gu-chelate and KOH cf. H. Mix and F.-W.Wilcke, H. 337, 40 (1964). 

Phalloidin is one of the poisons of the mushroom Amanita phaUoides with great toxicity. Only 50 pg are lethal for a mouse. Seven different amino acids are involved in its structure including such unusual hydroxy amino acids as hydroxy-leucine and allothreonine (T. Wieland). There is a bridge between tryptophan and the SH group of cysteine which yields hydroxy tryptophan upon hydrolysis. The formula is not reproduced here. 

The main representative of the phallotoxins, phalloidin, also contains, like all members of this group, a y-hydroxy-leucine residue. It has been found extremely difficult to introduce this amino acid residue as a component of a peptide chain, because of its tendency to form a y-lactone ring. When the norvaline analog (norphalloin Fig. 10) was proved to be even more toxic than the natural toxins 113), the first synthesis of a phallotoxin had been achieved. Later on, a number of synthetic analogs of norphalloin were synthesized in order to obtain information on structure-activity relationships 115, 166, 427). 

Fig. 8. Stmcture of (a) valinomycin and (J3) and enniatins and beauvericin. Hov = a-hydroxy-isovaleric acid and Lac = lactic acid. The /V-methylamino acid for enniatin A is isoleucine enniatin B, valine enniatin C, leucine and beauvericin, phenylalanine.

Ubenimex, [(2(3),3(R))-3-amino-2-hydroxy-4-phenylbutanoyl]-L-leucine, was isolated as an inhibitor of aminopeptidases, on which it acts as a strong, reversible transition-state analogue inhibitor (293). Analogues of ubenimex have been made and some other aminopeptidase inhibitors, not all of them peptides, have been isolated from streptomycetes (294—296). 

PEPTIDE SYNTHESES USING N-ETHYL-5-PHENYLIS0XAZ0LIUM-3 -SULF0NATE CARBOBENZOXY-l-ASPARAGINYL-l-LEUCINE METHYL ESTER AND JV-CARBOBENZOXY-3-HYDROXY-l-PROLYLGLYCYLGLYCINE ETHYL ESTER... 

L-Leucine, N-[N2-[(phenylmethoxy)carbonyl]-L-asparginyl]-, methyl ester and Glycine, N- [3-hydroxy- l-f(phenylmethoxy) -carbonyl]-L-prolyl]-, ethyl ester]... 

As the name implies, the odor of urine in maple syrup urine disease (brancbed-chain ketonuria) suggests maple symp or burnt sugar. The biochemical defect involves the a-keto acid decarboxylase complex (reaction 2, Figure 30-19). Plasma and urinary levels of leucine, isoleucine, valine, a-keto acids, and a-hydroxy acids (reduced a-keto acids) are elevated. The mechanism of toxicity is unknown. Early diagnosis, especially prior to 1 week of age, employs enzymatic analysis. Prompt replacement of dietary protein by an amino acid mixture that lacks leucine, isoleucine, and valine averts brain damage and early mortality. 

Other workers began to study the structure of gramicidin. Christensen and coworkers12 isolated crystalline tryptophane and leucine from a hydrolysate. They found no evidence for a fatty acid component and established that phenylalanine, proline and hydroxyproline were absent from a hydrolysate. These workers isolated alanine diox-pyridate from a hydrolysate and also established that gramicidin contained a compound with vicinal hydroxy and amino groups. They speculated that this compound might be serine or isoserine and proposed that gramicidin contains two tryptophane, 2 leucine, 2 or 3 alanine and 1 hydroxyamino residues or a multiple of this composition. 

Hotchkiss114 isolated optically and analytically pure d-leucine from the hydrolysate. This was the first non-enzymatic proof that d-amino acids actually occurred in gramicidin. He also noted the presence of an amino-hydroxy compound, but indicated that it was not isoserine. 

Yeast isopropylmalate isomerase of the leucine biosynthetic pathway, which catalyzes a totally analogous reaction to that of aconitase, converts 3-hydroxy-3-carboxy-4-methylpentanoate to 2-hydroxy-3-carboxy-4-methylpentanoate via an allylic intermediate. In its initial characterization by EPR spectroscopy, a high-field shift in its EPR signal from a g-average of 1.96 to 1.90 is seen upon addition of substrate (70). This result suggests that its mechanism is the same as that found for aconitase. 

Cyclosporine A Cyclosporine A, [R-[R, R -(E)]]-cyclo-(L-alanyl-D-alanyl-iV-methyl-L-leucyl-iV-methyl-L-leucyl-A-methyl-L-valyl-3-hydroxy-iV,4-dimethyl-L-2-amino-6-octenoyl-L-a-aminobutyryl-A-methylglycyl-iV-methyl-L-leucyl-L-valyl-iV-methyl-L-leucine) (31.2.2), is extracted from a cultural liquid of products of the vital activity of the mushroom Tolypocladium inflatum [14-17], and which is also proposed to obtain synthetically [18-20]. 

Figure 9-4. Metabolism of the branched-chain amino acids. The first two reactions, transamination and oxidative decarboxylation, are catalyzed by the same enzyme in all cases. Details are provided only for isoleucine. Further metabolism of isoleucine and valine follows a common pathway to propionyl CoA. Subsequent steps in the leucine degradative pathway diverge to yield acetoacetate. An intermediate in the pathway is 3-hydroxy-3-methylglutaryl CoA (HMG-CoA), which is a precursor for cytosolic cholesterol biosynthesis.

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. 

Hi. Lysine. Gamma radiolysis of aerated aqueous solution of lysine (94) has been shown, as inferred from iodometric measurements, to give rise to hydroperoxides in a similar yield to that observed for valine and leucine. However, attempts to isolate by HPLC the peroxidic derivatives using the post-column derivatization chemiluminescence detection approach were unsuccessful. This was assumed to be due to the instability of the lysine hydroperoxides under the conditions of HPLC analysis. Indirect evidence for the OH-mediated formation of hydroperoxides was provided by the isolation of four hydroxylated derivatives of lysine as 9-fluoromethyl chloroformate (FMOC) derivatives . Interestingly, NaBILj reduction of the irradiated lysine solutions before FMOC derivatization is accompanied by a notable increase in the yields of hydroxylysine isomers. Among the latter oxidized compounds, 3-hydroxy lysine was characterized by extensive H NMR and ESI-MS measurements whereas one diastereomer of 4-hydroxylysine and the two isomeric forms of 5-hydroxylysine were identified by comparison of their HPLC features as FMOC derivatives with those of authentic samples prepared by chemical synthesis. A reasonable mechanism for the formation of the four different hydroxylysines and, therefore, of related hydroperoxides 98-100, involves initial OH-mediated hydrogen abstraction followed by O2 addition to the carbon-centered radicals 95-97 thus formed and subsequent reduction of the resulting peroxyl radicals (equation 55). 

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