(2S)-2-Amino-4,4-dimethylpentanoic acid

White to off-white powder

General procedure: To a 5 mL vial equipped with a magnetic stirrer bar were added 3-cyclohexyl-2-oxopropanoic acid (1j) (0.0510 g, 0.30 mmol), 2, 2-diphenylglycine (2) (0.0681 g, 0.30 mmol), chiral pyridoxamine 6g (0.0195 g, 0.030 mmol), and MeOH-H2O (8:2) (3.0 mL). The mixture was stirred at 20 °C for 3 days. The reaction mixture was transferred to a 25 mL round-bottom flask and MeOH was added until all the solid was dissolved. Then silica gel (0.50 g) was added. After removal of the solvent in vacuo at 20 °C, the resulting residue was submitted to column chromatography on silica gel (EtOH/ethyl acetate/25-28percent ammonia solution =100:58:16) to give compound 3j (0.0401 g, 78percent yield, 52percent ee) as a white solid. The enantiomeric excesses of 3b-k were deteremined by HPLC analysis after being converted to N-benzoyl methyl esters by treatment with thionyl chloride in methanol and subsequent reaction benzoyl chloride.7 The enantiomeric excess of 3a was deteremined by HPLC analysis after being converted to its methyl ester by treatment with CH2N2 in methanol.Screening of nitrilases against target substrate 4-methyl-D-leucine and 4-methyl-L-leucine (0269) Hydrolysis of 2-amino-4, 4-dimethyl pentanenitrile was performed by several of the nitrilases. Of these, some were shown to hydrolyse the nitrile to the L-isomer of the corresponding acid and were selected for further characterization. [tabl0013-en] Table 10. Summary of hit enzymes for enantioselective hydrolysis of 2-amino-4, 4-dimethyl pentanenitrileSEQ ID NOS: Conversion To Product (percent) Time For Highest Conversion (h) ee (percent) Turnover (g Product/kg Nitrilase/h) Specific Activity (µmol Product/mg Nitrilase/h) ConditionsScreening of nitrilases against target substrate 4-methyl-D-leucine and 4-methyl-L-leucine (0269) Hydrolysis of 2-amino-4, 4-dimethyl pentanenitrile was performed by several of the nitrilases. Of these, some were shown to hydrolyse the nitrile to the L-isomer of the corresponding acid and were selected for further characterization. [tabl0013-en] Table 10. Summary of hit enzymes for enantioselective hydrolysis of 2-amino-4, 4-dimethyl pentanenitrileSEQ ID NOS: Conversion To Product (percent) Time For Highest Conversion (h) ee (percent) Turnover (g Product/kg Nitrilase/h) Specific Activity (µmol Product/mg Nitrilase/h) ConditionsGeneral procedure: To a 5 mL vial equipped with a magnetic stirrer bar were added 3-cyclohexyl-2-oxopropanoic acid (1j) (0.0510 g, 0.30 mmol), 2, 2-diphenylglycine (2) (0.0681 g, 0.30 mmol), chiral pyridoxamine 6g (0.0195 g, 0.030 mmol), and MeOH-H2O (8:2) (3.0 mL). The mixture was stirred at 20 °C for 3 days. The reaction mixture was transferred to a 25 mL round-bottom flask and MeOH was added until all the solid was dissolved. Then silica gel (0.50 g) was added. After removal of the solvent in vacuo at 20 °C, the resulting residue was submitted to column chromatography on silica gel (EtOH/ethyl acetate/25-28percent ammonia solution =100:58:16) to give compound 3j (0.0401 g, 78percent yield, 52percent ee) as a white solid. The enantiomeric excesses of 3b-k were deteremined by HPLC analysis after being converted to N-benzoyl methyl esters by treatment with thionyl chloride in methanol and subsequent reaction benzoyl chloride.7 The enantiomeric excess of 3a was deteremined by HPLC analysis after being converted to its methyl ester by treatment with CH2N2 in methanol.Screening of nitrilases against target substrate 4-methyl-D-leucine and 4-methyl-L-leucine (0269) Hydrolysis of 2-amino-4, 4-dimethyl pentanenitrile was performed by several of the nitrilases. Of these, some were shown to hydrolyse the nitrile to the L-isomer of the corresponding acid and were selected for further characterization. [tabl0013-en] Table 10. Summary of hit enzymes for enantioselective hydrolysis of 2-amino-4, 4-dimethyl pentanenitrileSEQ ID NOS: Conversion To Product (percent) Time For Highest Conversion (h) ee (percent) Turnover (g Product/kg Nitrilase/h) Specific Activity (µmol Product/mg Nitrilase/h) ConditionsScreening of nitrilases against target substrate 4-methyl-D-leucine and 4-methyl-L-leucine (0269) Hydrolysis of 2-amino-4, 4-dimethyl pentanenitrile was performed by several of the nitrilases. Of these, some were shown to hydrolyse the nitrile to the L-isomer of the corresponding acid and were selected for further characterization. [tabl0013-en] Table 10. Summary of hit enzymes for enantioselective hydrolysis of 2-amino-4, 4-dimethyl pentanenitrileSEQ ID NOS: Conversion To Product (percent) Time For Highest Conversion (h) ee (percent) Turnover (g Product/kg Nitrilase/h) Specific Activity (µmol Product/mg Nitrilase/h) ConditionsMethod 27 tert-Butyl 4-methylleucinate 4-Methylleucine (500mg, 3.44mmol) was suspended in 10 ml t-butyl acetate. Perchloric acid (0.2ml, 3.49mmol) was added and the flask was stopped with a septum and stirred over night. Analysis was performed using TLC (DCM:MeOH, 9:1; staining with a ninhydrine/EtOH solution). The solution was poured into a flask containing 30ml EtOAc and 30 ml 5% Na2CO3. The aq-layer turned acidic and 2M NaOH was added until pH was approximately 7. The phases were separated and the aq-phase was washed with 2x30ml EtOAc. The combined organic phases were washed with brine, dried with Na2SO4 and evaporated. A oil was obtained which was co-evaporated with toluene and then with diethyl ether before being placed under vacuum for two days. Mass 665 mg (96% yield). NMR (CDCl3): 1.0 (s, 9H), 1.5 (s, 9H), 1.65-1.95 (m, 2H), 3.82 (t, 1H).

Molecular Weight:145.20
XLogP3:-1.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:145.110278721
Monoisotopic Mass:145.110278721
Topological Polar Surface Area:63.3
Heavy Atom Count:10
Complexity:126
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes