And polyleucine

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Biomimetic reactions should also be considered for the preparation of optically active cyanohydrins (using a cyclic dipeptide as catalyst) and also for the epoxidation of a, (3-unsaturated ketones (using polyleucine or congener as a catalyst). 

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

Some of the practicals describe the use of similar catalysts and/or catalysts that accomplish the same task. This has been done purposely to try to get the best match between the substrate described and the one being considered by an interested reader. Moreover when catalysts can be compared, this has been done. Sometimes a guide is given as to what we found to be the most useful system in our hands. In this context, it is important to note that, except for polyleucine-catalysed oxidations and the use of a bicyclic bisphosphinite for asymmetric hydrogenation, the Liverpool group had no previous experience in... 

Their studies involved the partial polymerization of NCAs of mixtures of specific amino adds having known e.e.s, followed by determination of the e.e.s of the amino adds in both the resulting polypeptides and in the residual unreacted NCA monomers. [94] In a typical experiment it was found that when an optically impure leucine NCA monomer having an l > d e.e. of 31.2% was polymerized to the extent of 52 % to the helical polyleucine peptide, the e.e. of the polymer was enhanced to 45.4 %, an increase of 14.2 %. In the same experiment the e.e. of the unreacted leucine NCA monomer was depleted to a similar extent. Analogous experiments with valine NCAs of known e.e.s, however, led to a reverse effect, namely, the preferential incorporation of the racemate rather than one enantiomer into the growing polyvaline peptide. This finding was interpreted to be the result of the fact that polyvaline consists of (3-sheets rather than a-helices, emphasizing that the Wald mechanism applies only to a-helix polymers. At about the same time Brach and Spach [95] showed that, under proper conditions, (3-sheet polymers could also be implicated in the amplification of amino add e.e.s. 

In determining the diversity of reactions which may be catalysed by polyleucine, it has been shown that the oxidation of sulfides to sulfoxides can be performed, achieving excellent levels of asymmetric induction. Thus, when polyleucine is coated onto a platinum electrode, oxidation of sulfides to optically active sulfoxides has been achieved in 77% e.e. and 56% yield, (Scheme 11) [22]... 

The use of a polyamino acid such as polyleucine as a catalyst for the asymmetric epoxidation of a,/l-unsaturated ketones is clearly established. The advantages and disadvantages of this methodology may be summarised as follows ... 

REGIO- AND STEREO-CONTROLLED OXIDATIONS AND REDUCTIONS 6.11.1 PREPARATION OF POLYLEUCINE-HYDROGEN PEROXIDE GEL... 

Poly-(L)-leucine-l,3-diaminopropane (740mg, O.lOmmol, 1.0mol%) and tetrabutylammonium hydrogen sulfate (l.Og, 2.95 mmol, 30mol%) were placed in a flask with a stirrer bar. Toluene (2 ml), sodium hydroxide solution (5M, 30 ml, 10 eq.) and aq. hydrogen peroxide (30%, 15 ml, 10 eq.) were added and stirred for three hours. The aqueous layer was removed and sodium hydroxide solution (5M, 30 ml, 10 eq.) and aq. hydrogen peroxide (30%, 15 ml, 10 eq.) were added and the mixture was stirred overnight. The aqueous layer was removed to leave the activated polyleucine gel. 

A solution of phenyl(3-pyridyl) vinyl sulfone (2.50 g) in toluene (5 ml) was added to the stirred polyleucine-hydrogen peroxide gel suspension in toluene. The mixture was stirred at room temperature for six hours and the reaction followed by TLC (eluent 60% ethyl acetate in hexane, vis. CAN). The product was isolated by hltration through Celite washing with ethyl acetate, drying over magnesium sulfate and concentration in vacuo. 

The Julia-Colonna method, which uses polyleucine, can form an epoxide from a chalcone (Scheme 9.17).126-132 However, the method is limited to aryl-substituted enones and closely related systems, and even then scale up of the procedure has been found to be problematic.133 The product of the epoxidation 14 has been used in a synthesis of (+)-clausenamide (15).134... 

H202 are required [72]. These authors also investigated the effect of the method used for the preparation of polyleucine, and found that material made by high-temperature polymerization gave the best results. Much lower loadings of polyleucine can now be used (down to 0.5 mol% for chalcone epoxidation). The same group has carried out the process on the 100-g scale [73]. Although these conditions have not yet been tested as widely as the Roberts biphasic ones, a non-chalcone substrate was reported (Scheme 12.16). 

The mechanism of the polyleucine-catalyzed epoxidation is still under investigation [74]. Kinetic studies indicate that the reaction proceeds via the reversible addition of chalcone to a polyleucine-bound hydroperoxide [75]. Recent discussions have included studies of asymmetric amplification polyleucine derived from non-enantiopure amino acid shows highly amplified epoxide enantiomeric excess, and the results fit a mathematical model requiring the active catalyst to have five terminal homochiral residues, as rationalized by molecular modeling studies [76]. 

Could similar channels be produced in the bilayer membranes of primitive cells There is no doubt that channel-like defects appear when a nonpolar peptide interacts with a lipid bilayer. For instance, polyleucine or polyalanine has been induced to fuse with planar lipid membranes, and the bilayers exhibited transient bursts of proton conductance [43]. Surprisingly, channellike conductance also appears when RNA is selected for its ability to bind to phospholipids [44], From these observations it is fair to say that if random polymers were being produced by some unknown synthetic reaction on the early Earth, some of those polymers were likely to have been able to penetrate bilayer membranes and produce channels that bypassed the permeability barrier. This is an area that is ripe for further investigations, as described in a recent review by Pohorille et al. [45]. 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

Figure 6.16 Organization of fully interdigitated, side by side a-helices on the water surface at the inflection point ( 2.S A /residue for polyalanine and 17.0 for polyleucine). The views are perpendicular and parallel to the water surface.

High enantioselectivity and good yields have been obtained in asymmetric epoxidation of enones. Roberts modification of the Julia epoxidation using an immobilized polyleucine catalyst now represents a simple, practical method for enone epoxidation. Of the metal-based systems, the most economical and practical method is probably Enders protocol, despite the fact that it uses stoichiometric amounts of metal and hgand, as all the reagents are commercially available and cheap. It is difficult to compare the polypeptide-based catalysts with the metal based catalysts in terms of overall efficiency. 

For epoxidation of enones and related substances with alkaline hydrogen peroxide, polyleucine exerts desirable effects, yielding products with greater than 90% ee. " Enone epoxidation with oxygen in the presence of EtjZn and R,R)-N-methylpseudoephedrine is also satisfactory. 

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