Amino acid enantiomers continued

Boersma, A. J. Bayley, H. Continuous stochastic detection of amino acid enantiomers with a protein nanopore. Angew Chem IntEd 2012, 51, 9606-9609. 

It is well-known that catalytic amounts of aldehyde can induce racemization of a-amino acids through the reversible formation of Schiff bases.61 Combination of this technology with a classic resolution leads to an elegant asymmetric transformation of L-proline to D-proline (Scheme 6.8).62 63 When L-proline is heated with one equivalent of D-tartaric acid and a catalytic amount of n-butyraldehyde in butyric acid, it first racemizes as a result of the reversible formation of the proline-butyraldehyde Schiff base. The newly generated D-proline forms an insoluble salt with D-tartaric acid and precipitates out of the solution, whereas the soluble L-proline is continuously being racemized. The net effect is the continuous transformation of the soluble L-proline to the insoluble D-proline-D-tartaric acid complex, resulting in near-complete conversion. Treatment of the D-proline-D-tartaric acid complex with concentrated ammonia in methanol liberates the D-proline (16) (99% ee, with 80-90% overall yield from L-proline). This is a typical example of a dynamic resolution where L-proline is completely converted to D-proline with simultaneous in situ racemization. As far as the process is concerned, this is an ideal case because no extra step is required for recycle and racemization of the undesired enantiomer and a 100% chemical yield is achievable. The only drawback of this process is the use of stoichiometric amount of D-tartaric acid, which is the unnatural form of tartaric acid and is relatively expensive. Fortunately, more than 90% of the D-tartaric acid is recovered at the end of the process as the diammonium salt that can be recycled after conversion to the free acid.64... 

Despite the fact that thioesters of optically active amino acids have long been known to racemize promptly even in the presence of rather weak bases [48], and that they are able to act as irreversible acyl donors in enzyme-mediated acyl transfers [49], it was only in 1995 that they were reported to be good substrate candidates for DKR, where they are continuously racemized by an organic base while a hydrolytic enzyme acts preferentially on one of the two enantiomers [50]. In later works, the same authors reported on a more detailed and systematic study of the same reaction system applied to a broader array of substrates. The reactions were ran in a biphasic water/toluene mixture in the presence of trioctylamine as a hydrophobic organic base, so that the substrate racemization takes place in the organic phase while the hydrolysis product is continuously extracted into the water phase. Under racemizing conditions, the authors obtained almost complete conversion and significantly better optical purity (Scheme 8.8) [51], which is attributable to the continue depletion of the unreactive substrate enantiomer. 

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