Amino adds racemization

Elster, H. 1990 Age determination offossil bone by amino add racemization. Ph.D. dissertation, Weizmann Institute, Rehovot. 

The enantioselective binding properties of certain chiral crown ethers have been employed in the resolution of amino add racemates. The racemic amino ester is adsorbed onto silica gel as its ammonium salt and eluted by a chloroform solution of the chiral crown ether. An excellent separation of the two enantiomers is achieved by this method (74JA7100). 

However, the products are separated using ion-exchange columns and the starting material is a derivative rattier than a precursor of the racemic amino add, thus making the total process drcuitous since it involves several chemical steps in addition to die enzymatic resolution step. Furthermore, racemisation of the unwanted isomer is not easily accomplished. 

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. 

Amides and peptides1 Amides are obtained in 93-96% yield by reaction of 1 and N(C2H5)3 with carboxylic acids and amines in DMF (preferred solvent). A similar condensation of amino acid esters and Boc- or Cbo-amino adds proceeds in 91-96% yield and with practically no racemization. 

This is caused by the two enantiomers of Nobin forming a very stable - but catalytically inactive - heterochiral dimer, thus removing the minor enantiomer of Nobin from the catalytic cycle and leaving the major enantiomer of Nobin to form a complex with the sodium ion and the enolate of substrate 11a. From a practical perspective, the non-linear effect means that amino adds with essentially identical enantiomeric excesses are obtained whether the Nobin catalyst is enantiomerically pure or has an enantiomeric excess of just 30%. Since Nobin is prepared as a racemate [26,27] and must be resolved [27,28] prior to use, this is a major synthetic... 

A. Matsuyama and S. Tokuyama, Methods for racemizing N-acylamino adds and produdng optically active amino adds,... 

The four-step synthesis of a, -diaminocaprolactam shown in Figure 5.29 is part ofa chemoenzymatic route to (S)-lysine, an essential amino add in our diet [135], The racemic caprolactam (azepan-2-one) product is then hydrolyzed selectively to (S)-lysine, using an immobilized (S)-hydrolase enzyme. 

As for the induction, type I looks promising, one of the diastereotopic faces of the corresponding anion is shielded by the tiny hydrogen, the other by the much bulkier R1 which can be chosen rather freely. — Type II consists of an optically active ct-methylamino acid which is the chiral auxiliary and contributes C-3 and of a racemic amino add that contributes C-6. 

If a C3 unit needs to be introduced bearing a carbon chain, then there are several options. A P-amino add could be used as a precursor in a parallel synthesis to those discussed above. Alternatively, a strategy based on malonate syntheses could be employed. Co-condensation of a C-substituted malonate with a primary diamine in boiling ethanol gives reasonable yields of cyclic diamide which may be reduced with borane in THF to yield the desired polyamine (Scheme 1.12 and Protocol 5).18 Another possibility is to prepare a linear bis-toluenesulfonate ester from a malonate by reduction (e.g. LiBH4) and tosylation, followed by a standard toluenesulfonamide cyclisation reaction. Yet another variant, this time giving racemic product, is to react a coumarin derivative with a linear polyamine (Scheme 1.12).1819 In this case, a... 

Enzymatic Kinetic Resolution of N-Boc-Amino Add-Thioesters Coupled with Base-catalyzed Racemization Recently, a new method leading to the preparation of a number of aryl-glycines of the L-configuration has been published. The method is based on the hydrolysis of N-Boc-amino acid thioesters 15 catalyzed by an industrial preparation of the protease subtilisin (Scheme 13.16) [43]. 

Trost, E.M. and Fischer, L. (2002) Minimization of by-product formation during D-aminoadd oxidase catalyzed racemate resolution of D/L-amino adds. Journal of Molecular Catalysis B ... 

Similarly, conversion of A -acetyl amino acid esters into the related A/ -Boc-protected derivatives is performed with B0C2O/DMAP which in the first step leads to acylation of the acetyl amide group. This is then in turn hydrolyzed with hydrazine or lithium hydroxide to produce the A -Boc-protected amino add ester or free carboxy derivative, respectively (Scheme 32). No racemization was detected under these reaction conditions.t ... 

Threonine contains a sterically hindered and therefore less reactive hydroxy group. The O-acylation of unprotected threonine during coupling reactions is therefore less problematic, but can nevertheless occur. Noncoded hydroxy amino acids containing a secondary hydroxy group have a reactivity similar to threonine. These hydroxy amino adds contain an additional asymmetric center at the (3-carbon atom. In the case of reactions on the secondary hydroxy group, this center is accessible to racemization, e.g. threonine can be converted into allo-threonine. 

To circumvent or minimize this side reaction, an excess of the reagent should also be avoided. Further it is recommended that the amino acid to be activated is first added to the resin or alternatively, the amino add and activator are first mixed prior to addition to the amino component. However, the increased risk of racemization caused by the preactivation process should also be considered. ... 

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