Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines

Abstract

Immobilised whole-cell (R)-transaminases (TAs) enabled synthesis of either (R)- or (S)-enantiomers of drug-like amines from prochiral ketones or from racemic amines, respectively, in >95% ee.

Enantioselective Chromatographic Separation and Lipase Catalyzed Asymmetric Resolution of Biologically Important Chiral Amines

“…Yield (117 mg, 50%), 1 H NMR (400 MHz, CDCl 3 ) δ 7.51-7.17 (m, 2H), 7.17-6.82 (m, 3H), 4.98 (s, 1H), 3.37 (s, 2H), 1.44 (s, 3H).…”

“…Yield (113 mg, 45%), 1 H NMR (400 MHz, CDCl 3 ) δ 6.89-6.82 (m, 2H), 6.74 (d, J = 8.8, 2.2 Hz, 1H), 6.59 (d, J = 5.9 Hz, 1H), 5.06 (p, J = 7.1 Hz, 1H), 3.42 (s, 2H), 1.53 (d, J = 10.9 Hz, 3H).…”

“…Yield (100 mg, 38%), 1 H NMR (400 MHz, CDCl 3 ) δ 8.39 (dd, J = 4.8, 1.6 Hz, 1H), 8.34 (d, J = 1.9 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.42 (s, 1H), 7.24 (dd, J = 7.8, 4.9 Hz, 1H), 4.21 (dt, J = 13.6, 6.8 Hz, 1H), 3.34 (s, 2H), 2.85-2.69 (m, 2H), 1.17 (d, J = 6.7 Hz, 3H).…”

“…Chiral aromatic amines and their amides are found in around 40% of all active pharmaceutical ingredients [1,2] and are represented in many biologically important compounds, such as the natural products dysidenin, the antidiabetic repaglinide, the antidementia rivastigmine, the calcimimetic cinacalcet, and other drugs, as per Figure 1 [3]. Moreover, 1-arylpropan-2-amines symbolize a key pharmacophore in drugs used in the treatment of sleep disorders, depression, obesity, central and peripheral stimulant activity via affecting both serotonin (5-HT) receptor and monoamine oxidase (MAO) enzyme [4,5].…”

“…Despite the wide applicability of chemical catalysis in asymmetric synthesis, biocatalysis has been introduced as a superior alternative to chemical catalysis and found plentiful applications in numerous fields particularly to make chiral building blocks for the pharmaceutical industry [13,14]. Of these building blocks, chiral amines were displayed as one of the most prominent examples where a plethora of biocatalysts have been implemented [1,[15][16][17].…”