Succinic acid
Succinic acid
110-15-6
disodium succinate
Phthalocyanine pigment
Compound dyes
Compound green
Composite blue
The example of Protease inhibiting succinic acid(cas:110-15-6) derivatives
Release time:2016/8/1 17:45:52


The example of Protease inhibiting succinic acid derivatives

Example 2
1-Amino-3(S)-(dibenzylamino)-4-phenyl-2(R)-butanol

A solution of 3(S)-(dibenzylamino)-2(R)-hydroxy-4-phenylbutanenitrile [50.82 g, 143 mmol] described by M. T. Reetz et al., Tetrahedron Lett., 29, 3295 (1988)] in anhydrous Et2 O (250 mL) was added dropwise over a period of 2 h to a stirred, cooled (0°) mixture of LiAlH4 (8.10 g, 213 mmol) and anhydrous Et2 O (500 mL). The mixture was allowed to warm to room temperature while being stirred for 4.5 h. The mixture was cooled again to 0°. EtOAc (100 mL) was added slowly over 15 min. Stirring was continued for 15 min at 0°. A cold (0°) solution of 2N NaOH (250 mL) was added dropwise to the reaction mixture giving a white suspension/emulsion. The cloudy organic supernatant was separated and the remainder of the suspension/emulsion was passed through a 45 μm filter. The filtrate was extracted with EtOAc and the extract was combined with the first organic phase. After drying over NaCl/Na2 SO4, the solution was concentrated to a volume of ca 100 mL and allowed to stand at 5° for 18 h. The precipitated material was separated, triturated with hexane (300 mL), collected by filtration, and dried under reduced pressure to give the title compound as a white solid (34 g, 66% yield). Mp: 72°-76°. [α]D24 -1.9° (c=1, MeOH). [α]Hg36524 -24.0° (c=1, MeOH). 1 H NMR (CDCl3, 400 MHz) δ 2.68 (dd, J=12.6, 7.6, 7.2 Hz, 1H), 2.81 (dd, J=12.6, 3.8, 3.5 Hz, 1H), 2.86-3.00 (m, 2H), 3.08 (dd, J=14.1, 7.6, 7.3 Hz, 1H), 3.59 (d, J=13.7 Hz, 2H), 3.69 (m, 1H), 3.71 (d, J=13.7 Hz, 2H), 7.16-7.35 (m, 15H). FAB-MS (m/z): 361 (M+H)+.


Example 3
N4 -[3(S)-(Dibenzylamino)-2(R)-hydroxy-4-phenylbutyl]-N1
-(1-ethylpropyl)-3(R)-tert-butylbutaneamide

A solution of 1-amino-3(S)-(dibenzylamino)-4-phenyl-2(R)-butanol (5.00 g, 13.9 mmol; described in example 2), 4-(1-ethylpropylamino)-2(R)-tert-butyl-4-oxobutanoic acid (3.70 g, 15.2 mmol; described in example 1), TBTU (5.30 g, 16.5 mmol) and N-methylmorpholine (6 mL, 54.5 mmol) in acetonitrile (60 mL) was stirred 18 h at room temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in EtOAc. The solution was washed with 1N aqueous ammonia (4×) and brine (2×). After drying over a mixture of decolorizing charcoal and Na2 SO4, the solvent was removed under reduced pressure. The residue was purified by flash chromatography using 8:2 hexanes/EtOAc (8:2) followed by hexanes/EtOAc (1:1) as eluants. After combining the appropriate fractions and removing the solvent, the resulting yellow residue was triturated with hexanes and dried under reduced pressure to give the title compound as a white solid (4.43 g, 55% yield). Mp: 110°-112° . [α]D24 +6° (c=1, MeOH). 1 H NMR (CDCl3, 400 MHz) δ 0.82 (s, 9H), 0.86 (t, J=7.3 Hz, 3H), 0.88 (t, J=7.3 Hz, 3H), 1.23-1.38 (m, 2H), 1.43-1.58 (m, 2H), 1.95 (dd, J=11.6, 3.2, 2.9 Hz, 1H), 2.26 (dd, J=13.7, 2.9 Hz, 1H), 2.40 (dd, J=13.4, 11.8 Hz, 1H), 2.93 (m, 1H), 3.02 (m, 1H), 3.18 (dd, J=14.0, 4.1 Hz, 1H), 3.33 (dt, J=14.6, 4.7 Hz, 1H), 3.42 (d, J=13.4 Hz, 2H), 3.58 (broad s, 1H), 3.70 (d, J=13.4 Hz, 2H), 3.70-3.81 (m, 3H), 5.00 (broad t, J=5.5 Hz, 1H), 5.20 (d, J=9.2 Hz, 1H), 7.15 (d, J=7.0 Hz, 3H), 7.20-7.37 (m, 12H). FAB-MS (m/z): 586 (M+H)+.


Example 4
N4 -[3(S)-Amino-2(R)-hydroxy-4-phenylbutyl]-N1
-(1-ethylpropyl)-3(R)-tert-butylbutanediamide.
The title compound of example 3 (6.43 g, 10.97 mmol) was dissolved in MeOH (100 mL). 20% Pd(OH)2 /C (200 mg) and glacial acetic acid (5 mL) were added to the solution. The mixture was stirred under an atmosphere of H2 for 1.5 h. Thereafter, the mixture was filtered through a 45 μM membrane and the filtrate was concentrated under reduced pressure. The residue was dissolved in EtOAc. The solution was washed serially With an aqueous saturated solution of Na2 CO3 (3×20 mL) and brine (2×), dried (Na2 SO4 ) and concentrated to give a solid. Trituration of the solid with Et2 O afforded the title compound as a white powder (3.53 g, 79% yield) Mp 155°-158° . [α]D24 -14.0° (c=1, MeOH).1 H NMR(CDCl3, 400 MHz) δ 0.85 (t, J=7.3 Hz, 3H), 0.87 (t, J=7.3 Hz, 3H), 1.01 (s, 9H), 1.26-1.41 (m, 2H), 1.41-1.58 (m, 2H), 2.36 (dd, J=13.8, 2.9, 2.6 Hz, 1H), 2.43-2.50 (m, 2H), 2.60 (dd, J=13.8, 11.4 Hz, 1H) , 2.98-3.09 (m, 2H) , 3.15 (m, 1H), 3.52-3.60 (m, 2H) , 3.72 (m, 1H) , 5.40 (d, J=8.9 Hz, 1H), 6.50 (broad t, J=5.4 Hz, 1H), 7.18-7.33 (m, 5H). FAB-MS (m/z): 406 (M+H)+.

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