Chiral Amino Acids

Chiral Amino Acids

Amino acids are biologically important organic compounds containing functional groups of amino (-NH₂) and carboxyl (-COOH), and both amino and carboxyl groups are organic compounds directly attached to a -CH- structure. Amino acids containing a chiral carbon atom are referred to as chiral amino acids.

The amino acids obtained after proteolysis are all α-amino acids, which are the basic units that constitute proteins. All α-amino acids except glycine NH₂-CH₂-COOH are chiral amino acids.

Applications

• Catalytic Aldol condensation: L-proline can be used as a catalyst to directly catalyze the Aldol reaction of various aromatic aldehydes and acetone. The reaction conditions are mild and can be carried out in water to obtain higher product yield and e.e.value.

  Figure 1. Direct asymmetric aldol reactions catalyzed by L-valine

• Catalytic asymmetric addition reaction:The cyclo[S-amphetamine-(S)histidine] can be used as a catalyst to catalyze the asymmetric addition reaction of HCN and benzaldehyde. The catalyst exhibited good substrate suitability and the corresponding cyanohydrins were synthesized with higher enantiomeric purity.

  Figure 2. Asymmetric addition of hydrogen cyanide to benzaldehyde catalyzed by cyclo[S-amphetamine-(S)histidine]

• Catalytic epoxidation reaction: The highly enantioselective epoxidation of α-substituted styrene and aqueous hydrogen peroxide can be catalyzed by N-protected amino acids (AAs). The synergistic action of amino acids and central iron effectively activates hydrogen peroxide, catalyzing the epoxidation of a large number of less reactive substrates. The reaction yielded a higher product yield and the e.e. value reached over 97% in a short time.

  Figure 3. Chiral iron complex t and N-protected amino acids (AAs) as the catalys in the asymmetric epoxidation reaction

• Catalytic Michael esterification reaction：A tandem Michael lactone reaction of o-nitrovinylphenol and azalide can be catalyzed by a catalyst in which a tertiary leucine derivative is combined with an indoleamine. The reaction yield, corresponding selectivity, and diastereoselectivity are all high.

  Figure 4. Cascade Michael addition-lactonization reactions catalyzed by chiral squaramide derived from L-tert-leucine

• Catalytic asymmetric Mannich reaction: The use of proline as a catalyst can directly catalyze the asymmetric Mannich reaction of ketone, aldehyde, and amine, and synthesize a β-amino hydroxy compound with higher regioselectivity and better chemoselectivity.

  Figure 5. Asymmetric three-component Mannich reactions catalyzed by proline

Classification

Similar to hydroxy acids, chiral amino acids can be classified into α-, β-, γ-, ω-amino acids according to different positions of the amino group attached to the carbon chain. Chiral amino acids present in nature are mainly classified into essential amino acids and non-essential amino acids. In addition, it can also be divided into acidic, basic, neutral, and heterocyclic amino acids according to different chemical properties.

Production

The methods for preparing chiral amino acids mainly include biological fermentation, solid phase peptide method, NCA ring-opening polymerization method and the like. Most of the amino acids that make up the protein are biosynthesized as a carbon chain backbone by an intermediate between the Embden-Meyerhof pathway and the citric acid cycle. The exception is aromatic amino acids and histidine, the former biosynthesis is related to the pentose phosphate intermediate erythrose-4-phosphate, the latter is synthesized by ATP and phosphoribosyl pyrophosphate.

References

1. List B, Pojarliev P. (2002).”The proline-catalyzed direct asymmetric three-component Mannich reaction”. Journal of the American Chemical Society. 124(5): 827-833.
2. Cordova A, Sunden H.(2004). “The direct amino acid-catalyzed asymmetric incorporation of molecular oxygen to organic compounds”. Journal of the American Chemical Society. 126(29): 8914-8915.
3. Amedjkouh M.(2005). “Primary amine catalyzed direct asymmetric aldol reaction assisted by water”. Tetrahedron: Asymmetry. 16(8): 1411-1414.