Isoleucine derivatives

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,... 

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. 

Esters of -branched amino acids are obtained by highly enantioselective hydrogenation of a-acylaminoacrylatcs bearing different substituents at the ff-carbon using Rh complexes of Me-DuPHOS (XI) and Me-BPE (XV). The D-a//o-isoleucine derivative 17 with 98.2% ee is obtained from the (Z)-enamide 16, and the D-isoleucine... 

Scheme 5.15 No Irish type II fragmentation and Yang cyclization of isoleucine derivatives, illustrating the influence of conformational equilibria.

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 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. 

A. Clausen, T. Dowling, and G. Bicker, Description of the retention behavior and chromatographic measurement of the change in pK with temperature of a diastereomeric pair of isoleucine derivatives, J. Liq. Chromatogr. Relat. Technol. 25 (2002), 705. 

Waldmann and coworkers [104, 264, 289] and Cativiela and coworkers [286] proposed the use of acrylamides of a-aminoesters as dienophiles. Phenylalanine, valine and isoleucine derivatives lead to mediocre selectivities, but cy-doadditions of various dienes with a,P-unsaturated amides of (S)-proline benzyl or allyl esters 9.66 at 0°C are stereoselective. Obtaining different isomers depends on whether the Lewis acid is EtAlCh or TiCLj. These results have been interpreted by the approach of the diene to the least hindered face of either a monodentate complex (EtAlC ) or a chelate (TiC ). In both cases, the unsaturated amide is under... 

Several enantiopure guanidines were studied as the catalysts for the Henry reaction of dibenzylamino aldehydes with nitromethane. (R)-l-(l-Naphthyl)ethylamine-derived guanidine catalysed the reactions of L-isoleucine-derived aldehydes with good diastereos-electivity [42]. 

Spencer, K. C., and D. S. Seigler, Co-occurrence of valine/isoleucine-derived and cyclopentenoid cyanogens in a Passiflora species, Biochem. Syst. Ecol., 13, 303-304 (1985e). 

L-Valine and L-isoleucine derivatives Methacrylic acid (D 13) and tiglic acid (D 15) Synthesized in carabids, constituents of defense secretions... 

Rethinking suitable methods for the construction of a tertiary alkyl-aryl ether, 1 settled on an asymmetric allylation approach. The Trost ligand was known to favor formation of the branched adduct from unsymmetrical allyl donor substrates, and phenols had been successfully employed as nucleophiles. Accordingly, a retrosynthetic analysis suggested that a differentially protected dopa derivative 4 was required as the nucleophilic component, to be combined with a functionahzed isoleucine derivative containing either a branched (3a) or linear (3b) allyl donor component (Fig. 2). My first postdoc, Phihp Chan, embarked on the synthesis of such functionalized isoleucines in 2000 we were both rather green ... 

Just as Nathan started his PhD project in Melbourne, Wandless published the second total synthesis of ustiloxin D. The Wandless synthesis employed an AAA approach to the tertiary alkyl-aryl ether 25, but using a simpler substrate (24) than the functionalized isoleucine derivative we had been constructing (8, 9, or 14). Wandless subsequently converted the olefin in the AAA adduct 25 to the p-hydroxyisoleucine residue (i.e., 25—>27, Scheme 4). Though the AAA reaction proceeded with low diastereoselectivity (2 1), and the subsequent conversion of the olefin 25 to the a-amino acid 27 required multiple steps, the hallmark of the Wandless synthesis was the use of an Evans-Suga Al-catalyzed aldol-type reaction to generate the p-hydroxydopa residue... 

Despite Wandless synthesis employing a similar AAA approach to our proposed route, we decided to keep pursuing our AAA approach. We theorized that by using a fully functionalized isoleucine derivative (such as 9a) as the allyl donor, we could improve upon the convergency of Wandless route. Further, we hoped that the use of a more functionalized allyl donor, which was... 

Muramatsu, R., Misawa, S. andHayashi, H. Finding of an isoleucine derivative of a recombinant protein for pharmaceutical use. J. Pharm. Biomed. Anal. 31 979-987, 2003. 

Amino acids that have a branched alkyl side chain, such as valin, leucine, and isoleucine, are preferred. Especially isoleucine derivatives can show a large spontaneous polarization in the range of 300 nC/cm and more [24, 25]. 

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