Isovaline

The number of scientific articles published on meteorites has increased dramatically in the last few years few of these, however, concern themselves with small meteorites, the size of which lies between that of the normal meteorites (from centimetres to metres in size) and that of interplanetary dust particles. In the course of an Antarctic expedition, scientists (mainly from French institutions) collected micrometeorites from 100 tons of Antarctic blue ice (Maurette et al 1991). These micrometeorites were only 100 400 pm in size five samples, each consisting of 30-35 particles, were studied to determine the amount of the extraterrestrial amino acids a-aminoisobutyric acid (AIBS) and isovaline—both of which are extremely rare on Earth—which they contained. The analysis was carried out using a well-tested and extremely sensitive HPLC system at the Scripps Institute, La Jolla. Although the micrometeorites came from an extremely clean environment, the samples must have been contaminated, as they all showed traces of L-amino acids. Only one sample showed a significantly higher concentration of AIBS (about 280 ppm). The AIBS/isovaline ratio in the samples also lay considerably above that previously found in CM-chondrites. 

The variety of prebiotic organic reactions seems to be almost unlimited. Strasdeit et al. (2002) from the University of Hohenheim (Germany) reported the synthesis of zinc and calcium complexes of the amino acids valine and isovaline. They assume that these could have had a certain significance on the mineral-rich primeval Earth on heating to 593 K under nitrogen, valine was converted to the corresponding cyclic dipeptide. 

UV radiation hypothetical, but so is the transport of molecules from outer space to Earth. Recent analyses of the Murchison meteorite by two scientists from the University of Arizona, Tucson (Cronin and Pizzarello, 1997 Cronin, 1998) have shown it to contain the four stereoisomeric amino acids DL-a-methylisoleucine and DL-a-methylalloisoleucine. In both cases, the L-enantiomer is present in a clear excess (7.0 and 9.1%). Similar results were obtained for two other a-methyl amino acids, isovaline and a-methylvaline. Contamination by terrestrial proteins can be ruled out, since these amino acids are either not found in nature or are present in only very small amounts. Since the carbonaceous chondrites are thought to have been formed around 4.5 billion years ago (see Sect. 3.3.2), the amino acids referred to above must have been subject to one or more asymmetric effects prior to biogenesis. 

Probably the most recently discovered natural product of this class is FR235 222 (65) [79], a potent HDACi vith IC50 = 17nM. This compound differs from some of the other members of the class due to the isovaline and methyl proline moieties, although more markedly contains a a-hydoxyketone I-Ahoda amino acid as a zincchelating moiety. 

Especially in the case of high-molecular-weight surface-active substances (such as proteins), the period of change may be sufficiently prolonged to allow easy observation. This arises because proteins are surface active. All proteins behave as surface-active substances because of the presence of hydrophilic-lipophilic properties imparted from the different polar, such as glutamine and lysine, and apolar, such as alanine, valine, phenylalanine, isovaline, amino acids. Proteins have been extensively investigated as regards their polar-apolar characteristics as determined from surface activity. 

The helix-inducing effect of Aib has been compared to that of a number of other C -disubstituted glycines (Scheme 2) when incorporated in peptides. The helix-inducing ability of isovaline (Iva, 2) compares well to that of Aib and despite its chirality, it similarly exhibits a screw-sense indifference. 39,40 C -Methylvaline [(aMe)Val, 3], 40,41 C -methylleucine [(aMe)Leu], and C -methylphenylalanine [(aMe)Phe, 4]t40-42 aiso have helix-inducing abilities similar to that of Aib. Their helical propensities are higher than their unmethylated counterparts with L-(aMe)Val showing a clear-cut preference for the right-handed screw sense. 

L-amino acids, and in many cases also non-proteinogenic amino acids such as D-amino acids, oc-aminoisobutyric acid, isovaline, (3-alanine, and N-methylamino acids, serve as the raw materials for the production of peptides. The formation of the peptide linkage between the amino acids takes place in the following ways ... 

In 1872 the simplest a,a-disubstituted amino acid (2-aminoisobutyric acid, Aib) was described [3]. In 1908 the first optically active representative of this class of compounds, (/ )-2-ethylala-nine (D-isovaline), was isolated by microbial racemic resolution [4]. Synthetic chemists have therefore been interested in the enantiopure synthesis of a-alkylated a-amino acids for some time. Their powerful methods for the construction of chiral a-amino acids can in some cases also be used for the synthesis of the a-alkylated derivatives which has been the topic of recent reviews [5]. 

H3CCH2C(CH3)(NH2)C0- the acyl radical from isovaline used in naming peptides... 

Likely products of step 2, precipitates of Zn or Ca salts of amino acids valine and isovaline, were subjected to heating to 320°C in a nitrogen atmosphere (Strasdeit et al. 2001), causing complete thermolysis. Besides the simple diketopiperazines (cyclic dipeptides) and other peptides, heterocyclic compounds arise, and ketones (namely, the symmetrical Ruzicka products which form from Ca salts after desamination of the amino acids, like 2,8-dimethylnonan-5-on) and other prebiotically feasible small molecules. As might be anticipated, product yields and distribution sensitively depend on whether Zn or Ca ions were involved. There is some quite simple precondition for... 

The efficiency of the fluoride method was further confirmed by the synthesis of pep-taibols. These peptides are characterized by a high content of the C -dialkylamino acids Aib or isovaline and an amino alcohol at the C-terminus such as phenylalaninol (Pheol) or valinol (Valol). Degradation of the peptides in the final cleavage step due to the acid-labile Aib-Pro linkages,can be prevented by the use of the 2-chlorotrityl-resin.P l This achieves direct anchoring of Fmoc-protected amino alcohols which allows the final cleavage to occur under very mild conditions.P l... 

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