Abstract
Peptides are important compounds with broad applications in many areas. Asymmetric transamination of α-keto amides can provide an efficient strategy to synthesize peptides, however, the process has not been well developed yet and still remains a great challenge in both enzymatic and catalytic chemistry. For biological transamination, the high activity is attributed to manifold structural and electronic factors of transaminases. Based on the concept of multiple imitation of transaminases, here we report N-quaternized axially chiral pyridoxamines 1 for enantioselective transamination of α-keto amides, to produce various peptides in good yields with excellent enantio- and diastereoselectivities. The reaction is especially attractive for the synthesis of peptides made of unnatural amino acids since it doesn’t need great efforts to make chiral unnatural amino acids before amide bond formation.
Highlights
Peptides are important compounds with broad applications in many areas
We have proved that introducing an amine side arm to a chiral pyridoxamine can remarkably increase its activity and enantioselectivity for asymmetric transamination of α-keto acids[26] and have observed that quaternization of the pyridine N of a chiral pyridoxal leads to dramatical improvement of catalytic activity for asymmetric biomimetic Mannich reaction[60] and aldol reaction[61] of glycinate
The synthesis of chiral pyridoxamines 1 started with reductive amination of compound 526 to introduce the amine side chain
Summary
Peptides are important compounds with broad applications in many areas. Asymmetric transamination of α-keto amides can provide an efficient strategy to synthesize peptides, the process has not been well developed yet and still remains a great challenge in both enzymatic and catalytic chemistry. Enzymatic transamination is an important process to produce chiral amines such as amino acids in biological systems (Fig. 1b)[9,10], which is promoted by transaminases (Fig. 1c) with pyridoxal/pyridoxamine 5′-phosphates as the coenzyme[9,10,11,12,13]. On the basis of the structural characteristics of transaminases[46,47,48,49,50,53,54,55,56] as well as the previously reported studies[26,44,45,59,60,61,62], we has designed N-quaternized biaryl axially chiral pyridoxamines 1 bearing an amine side arm, mimicking transaminases in multiple aspects for catalytic asymmetric transamination of α-keto amides to peptides (Fig. 1c). Like the Lys residue does in biological transamination, the amine side arm can serve as an intramolecular base to facilitate 1,3-proton shift
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