N-Boc-L-Cysteine

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In an analogous manner to that described in Example 1, paragraphs (d) and g), by adding Boc-L-cysteine to benzyl 2-benzylacrylate and subsequently oxidizing with potassium monopersulphate triple salt there was obtained 3-[[(RS)-2-[(benzyloxy)carbonyl]-3-phenylpropyl]sulfonyl]-N-(tert-butoxycarbonyl)-L-alanine as a colourless oil, MS: 506 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In an analogous manner to that described in Example 1, paragraphs (d) and g), by adding Boc-L-cysteine to benzyl 2-benzylacrylate and subsequently oxidizing with potassium monopersulphate triple salt there was obtained 3-[[(RS)-2-[(benzyloxy)carbonyl]-3-phenylpropyl]sulfonyl]-N-(tert-butoxycarbonyl)-L-alanine as a colourless oil, MS: 506 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-t-butoxycarbonyl-L-cysteine [prepared from 58.6 g of L-cysteine p-toluenesulfonate, 50 g of di-t-butyl pyrocarbonate and 50 g of sodium bicarbonate in the manner described in Example 63(a)] was treated with 32 g of 1-nitro-2-(3-thienyl)ethylene and 6 g of sodium bicarbonate to give 74.8 g of the title compound as a syrup.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-t-butoxycarbonyl-L-cysteine [prepared from 58.6 g of L-cysteine p-toluenesulfonate, 50 g of di-t-butyl pyrocarbonate and 50 g of sodium bicarbonate in the manner described in Example 63(a)] was treated with 32 g of 1-nitro-2-(3-thienyl)ethylene and 6 g of sodium bicarbonate to give 74.8 g of the title compound as a syrup.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(tert-Butyloxycarbonyl)-L-cysteine (3.5 g, 15.8 mmol), benzyl 2-bromoacetate (3.7 g, 16.1 mmol) and triethylamine (1.8 g, 18.0 mmol) were dissolved in THF (100 ml). The mixture was stirred for 18 hours at room temperature then diluted with ethyl acetate (100 ml), washed with 0.3M KHSO4, sat NaHCO3, water and brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography on silica gel (eluant: 95% chloroform, 4% methanol, 1% acetic acid) to give a colourless oil identified as S-(benzyloxyrarbonylmethyl)-N-(tert-butyloxycarbonyl)-L-cysteine (5.2 g, 14.1 mmol, 89%). washed with 0.3M KHSO4 dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography on silica gel (eluant: 95% chloroform, 4% methanol, 1% acetic acid) to give a colourless oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(tert-Butyloxycarbonyl)-L-cysteine (3.5 g, 15.8 mmol), benzyl 2-bromoacetate (3.7 g, 16.1 mmol) and triethylamine (1.8 g, 18.0 mmol) were dissolved in THF (100 ml). The mixture was stirred for 18 hours at room temperature then diluted with ethyl acetate (100 ml), washed with 0.3M KHSO4, sat NaHCO3, water and brine, dried (Na2SO4) and evaporated in vacuo. The residue was purified by flash chromatography on silica gel (eluant: 95% chloroform, 4% methanol, 1% acetic acid) to give a colourless oil identified as S-(benzyloxyrarbonylmethyl)-N-(tert-butyloxycarbonyl)-L-cysteine (5.2 g, 14.1 mmol, 89%). washed with 0.3M KHSO4 dried (Na2SO4) evaporated in vacuo The residue was purified by flash chromatography on silica gel (eluant: 95% chloroform, 4% methanol, 1% acetic acid) to give a colourless oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In an analogous manner to that described in Example 1, paragraphs (d) and g), by adding Boc-L-cysteine to benzyl 2-benzylacrylate and subsequently oxidizing with potassium monopersulphate triple salt there was obtained 3-[[(RS)-2-[(benzyloxy)carbonyl]-3-phenylpropyl]sulfonyl]-N-(tert-butoxycarbonyl)-L-alanine as a colourless oil, MS: 506 (M+H)+.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-t-butoxycarbonyl-L-cysteine [prepared from 58.6 g of L-cysteine p-toluenesulfonate, 50 g of di-t-butyl pyrocarbonate and 50 g of sodium bicarbonate in the manner described in Example 63(a)] was treated with 32 g of 1-nitro-2-(3-thienyl)ethylene and 6 g of sodium bicarbonate to give 74.8 g of the title compound as a syrup.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Boc-L-Cys-OH (221 mg, 1.0 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added 10 N sodium hydroxide aq. (1.2 mL, 12 mmol) and 2-propane thiol (929 uL, 10 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 1 d with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated aq. NaS2O4 and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csp-OH (145.7 mg, 49% yield): 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.59 (br, s, 1H), 3.24-3.14 (m, 2H), 3.09-3.00 (m, 1H), 1.47 (s, 9H), 1.32-1.30 (dd, 6H); LRMS (ESI) m/z calcd for C11H22NO4S2 (M+H)+ 296.1. found 296.1. After removing THF under reduced pressure, reaction mixture The solution was extracted with EtOAc The extract was washed with saturated aq. NaS2O4 and brine dried over MgSO4 Concentration under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Boc-L-Cys-OH (221 mg, 1.0 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added 10 N sodium hydroxide aq. (1.2 mL, 12 mmol) and 2-propane thiol (929 uL, 10 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 1 d with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated aq. NaS2O4 and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csp-OH (145.7 mg, 49% yield): 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.59 (br, s, 1H), 3.24-3.14 (m, 2H), 3.09-3.00 (m, 1H), 1.47 (s, 9H), 1.32-1.30 (dd, 6H); LRMS (ESI) m/z calcd for C11H22NO4S2 (M+H)+ 296.1. found 296.1. After removing THF under reduced pressure, reaction mixture The solution was extracted with EtOAc The extract was washed with saturated aq. NaS2O4 and brine dried over MgSO4 Concentration under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Boc-L-Cys-OH (221 mg, 1.0 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added 10 N sodium hydroxide aq. (1.2 mL, 12 mmol) and 2-propane thiol (929 uL, 10 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 1 d with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated aq. NaS2O4 and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csp-OH (145.7 mg, 49% yield): 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.59 (br, s, 1H), 3.24-3.14 (m, 2H), 3.09-3.00 (m, 1H), 1.47 (s, 9H), 1.32-1.30 (dd, 6H); LRMS (ESI) m/z calcd for C11H22NO4S2 (M+H)+ 296.1. found 296.1. After removing THF under reduced pressure, reaction mixture The solution was extracted with EtOAc The extract was washed with saturated aq. NaS2O4 and brine dried over MgSO4 Concentration under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-2-((tert-butoxycarbonyl)amino)-3-mercaptopropanoic acid (Boc-L-Cys-OH) (110 mg, 0.5 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added sodium thiomethoxide (350 mg, 5.0 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 5.5 h with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated NaS2O4 aq. and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csm-OH (90.8 mg, 68% yield). 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.63 (br, s, 1H), 3.26-3.16 (m, 2H), 2.43 (m, 3H), 1.47 (s, 9H); LRMS (ESI) m/z calcd for C9H18NO4S2 (M+H)+ 268.1. found 268.2. After removing THF under reduced pressure, reaction mixture The solution was extracted with EtOAc The extract was washed with saturated NaS2O4 aq. and brine dried over MgSO4 Concentration under reduced pressure