(2R)-2-(2-methylpropanoylamino)-3-sulfanylpropanoic acid

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was synthesized by adapting, to N-isobutyryl-L-cysteine, the tritylation method described by K.-Y. Zee-Cheng and C. C. Cheng, J. Med. Chem., 1970, 13, 414-418. A suspension comprising 4.1 g (21.5 mmol) of N-isobutyryl-L-cysteine [(prepared according to H. Brückner et al., J. Chromatogr., 1989, 476, 73-82), ([α]D20=+84° (c 1, CHCl3))], 5.6 g (21.5 mmol) of triphenylmethanol and 16 ml of glacial acetic acid is stirred at ambient temperature. 4.1 ml (32.2 mmol) of BF3 etherate are added dropwise to the mixture while maintaining the temperature at 20-25° C. After stirring for 3 h, the brown solution obtained is subsequently cooled to 0° C. and then 70 ml of an aqueous sodium acetate solution and 140 ml of water are added. At the end of the additions, the reaction mixture sets solid in the form of a gel. This mixture is left overnight at 0° C. and then 150 ml of ice-cold water and 120 ml of ether are subsequently added with vigorous stirring. The ethereal phase is separated by settling and the aqueous waste liquors are washed with 4×80 ml of ether. The organic phases are combined, washed with 4×60 ml of ice-cold water, dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The crude product obtained is purified by washing successively with hexane (5×50 ml) to provide 13 in the form of a gum which is homogeneous by TLC with a yield of 81%. Rf (CH2Cl2/MeOH/AcOH, 9.4/0.6/0.07): 0.53. [α]D20=+21.40 (c 1.12, CHCl3). This compound was synthesized while maintaining the temperature at 20-25° C After stirring for 3 h the brown solution obtained is subsequently cooled to 0° C. The ethereal phase is separated the aqueous waste liquors are washed with 4×80 ml of ether washed with 4×60 ml of ice-cold water dried over sodium sulfate filtered evaporated to dryness under vacuum The crude product obtained is purified by washing successively with hexane (5×50 ml)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was synthesized by adapting, to N-isobutyryl-L-cysteine, the tritylation method described by K.-Y. Zee-Cheng and C. C. Cheng, J. Med. Chem., 1970, 13, 414-418. A suspension comprising 4.1 g (21.5 mmol) of N-isobutyryl-L-cysteine [(prepared according to H. Brückner et al., J. Chromatogr., 1989, 476, 73-82), ([α]D20=+84° (c 1, CHCl3))], 5.6 g (21.5 mmol) of triphenylmethanol and 16 ml of glacial acetic acid is stirred at ambient temperature. 4.1 ml (32.2 mmol) of BF3 etherate are added dropwise to the mixture while maintaining the temperature at 20-25° C. After stirring for 3 h, the brown solution obtained is subsequently cooled to 0° C. and then 70 ml of an aqueous sodium acetate solution and 140 ml of water are added. At the end of the additions, the reaction mixture sets solid in the form of a gel. This mixture is left overnight at 0° C. and then 150 ml of ice-cold water and 120 ml of ether are subsequently added with vigorous stirring. The ethereal phase is separated by settling and the aqueous waste liquors are washed with 4×80 ml of ether. The organic phases are combined, washed with 4×60 ml of ice-cold water, dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The crude product obtained is purified by washing successively with hexane (5×50 ml) to provide 13 in the form of a gum which is homogeneous by TLC with a yield of 81%. Rf (CH2Cl2/MeOH/AcOH, 9.4/0.6/0.07): 0.53. [α]D20=+21.40 (c 1.12, CHCl3). This compound was synthesized while maintaining the temperature at 20-25° C After stirring for 3 h the brown solution obtained is subsequently cooled to 0° C. The ethereal phase is separated the aqueous waste liquors are washed with 4×80 ml of ether washed with 4×60 ml of ice-cold water dried over sodium sulfate filtered evaporated to dryness under vacuum The crude product obtained is purified by washing successively with hexane (5×50 ml)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 35.2 g (0.20 mol) of L-cysteine hydrochloride monohydrate in 100 ml of a mixture of 80% of tetrahydrofuran (THF) and 20% of water was stirred under nitrogen at room temperature and treated with 44.0 g (0.40 mol) of sodium isobutyrate. The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen, 35 ml (0.21 mol) of isobutyryl anhydride was added dropwise. The resulting mobile suspension was stirred for 6h at room temperature, allowed to stand overnight, and finally heated under reflux for 4 h. The reaction mixture was cooled on an ice bath and 18 ml of concentrated hydrogen chloride was added. The organic phase was evaporated to give a colourless oil. The oil was washed with hexane and thereafter treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0, H2O, pH=7.0), 1H-NMR (CDCl3): δ 1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH). 13C-NMR (CDCl3): δ 19, 19.5; 26.5; 36; 54, 172, 178. ms: 335 (M+ +2TMS, after silylation). The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen finally heated under reflux for 4 h The reaction mixture was cooled on an ice bath The organic phase was evaporated to give a colourless oil The oil was washed with hexane treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0, H2O, pH=7.0), 1H-NMR (CDCl3): δ 1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 35.2 g (0.20 mol of L-cysteine hydrochloride monohydrate in 100 ml of a mixture of 80% of tetrahydrofuran (THF) and 20% of water was stirred under nitrogen at room temperature and treated with 44.0 g (0.40 mol of sodium isobutyrate. The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen, 35 ml (0.21 mol) of isobutyryl anhydride was added dropwise. The resulting mobile suspension was stirred for 6 h at room temperature, allowed to stand overnight, and finally heated under reflux for 4 h. The reaction mixture was cooled on an ice bath and 18 ml of concentrated hydrogen chloride was added. The organic phase was evaporated to give a colourless oil. The oil was washed with hexane and thereafter treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH). 13C-NMR (CDCl3): δ19, 19.5; 26.5; 36; 54, 172, 178. ms: 335 (M+ +2TMS, after silylation). The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen The resulting mobile suspension was stirred for 6 h at room temperature finally heated under reflux for 4 h The reaction mixture was cooled on an ice bath The organic phase was evaporated to give a colourless oil The oil was washed with hexane treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 35.2 g (0.20 mol of L-cysteine hydrochloride monohydrate in 100 ml of a mixture of 80% of tetrahydrofuran (THF) and 20% of water was stirred under nitrogen at room temperature and treated with 44.0 g (0.40 mol of sodium isobutyrate. The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen, 35 ml (0.21 mol) of isobutyryl anhydride was added dropwise. The resulting mobile suspension was stirred for 6 h at room temperature, allowed to stand overnight, and finally heated under reflux for 4 h. The reaction mixture was cooled on an ice bath and 18 ml of concentrated hydrogen chloride was added. The organic phase was evaporated to give a colourless oil. The oil was washed with hexane and thereafter treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH). 13C-NMR (CDCl3): δ19, 19.5; 26.5; 36; 54, 172, 178. ms: 335 (M+ +2TMS, after silylation). The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen The resulting mobile suspension was stirred for 6 h at room temperature finally heated under reflux for 4 h The reaction mixture was cooled on an ice bath The organic phase was evaporated to give a colourless oil The oil was washed with hexane treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 35.2 g (0.20 mol of L-cysteine hydrochloride monohydrate in 100 ml of a mixture of 80% of tetrahydrofuran (THF) and 20% of water was stirred under nitrogen at room temperature and treated with 44.0 g (0.40 mol of sodium isobutyrate. The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen, 35 ml (0.21 mol) of isobutyryl anhydride was added dropwise. The resulting mobile suspension was stirred for 6 h at room temperature, allowed to stand overnight, and finally heated under reflux for 4 h. The reaction mixture was cooled on an ice bath and 18 ml of concentrated hydrogen chloride was added. The organic phase was evaporated to give a colourless oil. The oil was washed with hexane and thereafter treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH). 13C-NMR (CDCl3): δ19, 19.5; 26.5; 36; 54, 172, 178. ms: 335 (M+ +2TMS, after silylation). The reaction mixture (white slurry) was cooled to 0°-5° C. and, under nitrogen The resulting mobile suspension was stirred for 6 h at room temperature finally heated under reflux for 4 h The reaction mixture was cooled on an ice bath The organic phase was evaporated to give a colourless oil The oil was washed with hexane treated with ether to give 12.9 g of the title compound as a white solid, mp 103°-104° C. (recrystallized from butyl acetate), [α]D25 =+23.4° C. (c 5.0 , H2O, pH=7.0), 1H-NMR (CDCl3): δ1.2 (6H, d, CH3), 1.4 (1H, t, SH), 2.5 (1H, sept, CH), 3.1 (2H, m, CH2), 4.9 (1H, dt, NCH), 6.7 (1H, d, NH), 10.6 (1H, s, OH)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was synthesized by adapting, to N-isobutyryl-L-cysteine, the tritylation method described by K.-Y. Zee-Cheng and C. C. Cheng, J. Med. Chem., 1970, 13, 414-418. A suspension comprising 4.1 g (21.5 mmol) of N-isobutyryl-L-cysteine [(prepared according to H. Brückner et al., J. Chromatogr., 1989, 476, 73-82), ([α]D20=+84° (c 1, CHCl3))], 5.6 g (21.5 mmol) of triphenylmethanol and 16 ml of glacial acetic acid is stirred at ambient temperature. 4.1 ml (32.2 mmol) of BF3 etherate are added dropwise to the mixture while maintaining the temperature at 20-25° C. After stirring for 3 h, the brown solution obtained is subsequently cooled to 0° C. and then 70 ml of an aqueous sodium acetate solution and 140 ml of water are added. At the end of the additions, the reaction mixture sets solid in the form of a gel. This mixture is left overnight at 0° C. and then 150 ml of ice-cold water and 120 ml of ether are subsequently added with vigorous stirring. The ethereal phase is separated by settling and the aqueous waste liquors are washed with 4×80 ml of ether. The organic phases are combined, washed with 4×60 ml of ice-cold water, dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The crude product obtained is purified by washing successively with hexane (5×50 ml) to provide 13 in the form of a gum which is homogeneous by TLC with a yield of 81%. Rf (CH2Cl2/MeOH/AcOH, 9.4/0.6/0.07): 0.53. [α]D20=+21.4° (c 1.12, CHCl3). This compound was synthesized while maintaining the temperature at 20-25° C After stirring for 3 h the brown solution obtained is subsequently cooled to 0° C. The ethereal phase is separated the aqueous waste liquors are washed with 4×80 ml of ether washed with 4×60 ml of ice-cold water dried over sodium sulfate filtered evaporated to dryness under vacuum The crude product obtained is purified by washing successively with hexane (5×50 ml)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The compound was prepared by the procedure given in Example 17, starting from L-cysteine and N-isobutyryl-L-cysteine. The compound was prepared by the procedure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of N-acetyl-L-cysteine (0.652 g, 4 mmol) and N-isobutyryl-L-cysteine (0.764 g, 4 mmol) in 10 mL of MeOH was stirred while hydrogen peroxide (30%, 0.60 mL, 5 mmol) was added dropwise. The stirring was continued for 3 hours at room temperature, after which the solvent was removed on the rotary evaporator. Addition of 25 mL of acetone and repeated evaporation afforded 1.5 g of crude material as an oil which solidified on standing. The desired title compound was isolated from this mixture by preparative HPLC as described in Example 17. was added dropwise after which the solvent was removed on the rotary evaporator Addition of 25 mL of acetone evaporation afforded 1.5 g of crude material as an oil which

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Isobutyryl-L-cysteine (9.5 g, 50 mmol) was dissolved in 50 mL of water. Hydrogen peroxide (30%, 3.1 mL, 30 mmol) was added and the reaction mixture was stirred at room temperature for 6 hours. After evaporation of the solvent under reduced pressure, a white crystallised oil (9.8 g) was obtained. Recrystallisation from ethyl acetate furnished the title compound as a white solid which was dried in vacuo. After evaporation of the solvent under reduced pressure a white crystallised oil (9.8 g) was obtained Recrystallisation from ethyl acetate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound was synthesized by adapting, to N-isobutyryl-L-cysteine, the tritylation method described by K.-Y. Zee-Cheng and C. C. Cheng, J. Med. Chem., 1970, 13, 414-418. A suspension comprising 4.1 g (21.5 mmol) of N-isobutyryl-L-cysteine [(prepared according to H. Brückner et al., J. Chromatogr., 1989, 476, 73-82), ([α]D20=+84° (c 1, CHCl3))], 5.6 g (21.5 mmol) of triphenylmethanol and 16 ml of glacial acetic acid is stirred at ambient temperature. 4.1 ml (32.2 mmol) of BF3 etherate are added dropwise to the mixture while maintaining the temperature at 20-25° C. After stirring for 3 h, the brown solution obtained is subsequently cooled to 0° C. and then 70 ml of an aqueous sodium acetate solution and 140 ml of water are added. At the end of the additions, the reaction mixture sets solid in the form of a gel. This mixture is left overnight at 0° C. and then 150 ml of ice-cold water and 120 ml of ether are subsequently added with vigorous stirring. The ethereal phase is separated by settling and the aqueous waste liquors are washed with 4×80 ml of ether. The organic phases are combined, washed with 4×60 ml of ice-cold water, dried over sodium sulfate, filtered and evaporated to dryness under vacuum. The crude product obtained is purified by washing successively with hexane (5×50 ml) to provide 13 in the form of a gum which is homogeneous by TLC with a yield of 81%. Rf (CH2Cl2/MeOH/AcOH, 9.4/0.6/0.07): 0.53. [α]D20=+21.40 (c 1.12, CHCl3). This compound was synthesized while maintaining the temperature at 20-25° C After stirring for 3 h the brown solution obtained is subsequently cooled to 0° C. The ethereal phase is separated the aqueous waste liquors are washed with 4×80 ml of ether washed with 4×60 ml of ice-cold water dried over sodium sulfate filtered evaporated to dryness under vacuum The crude product obtained is purified by washing successively with hexane (5×50 ml)