methyl (2R)-2-amino-3-sulfanylpropanoate

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

Procedure: To a solution of 7 g of rifamycin S in 200 ml of methanol a mixture was added containing 1.8 g of the hydrochloride of cysteine methyl ester and 1.53 g of triethylamine. The mixture was refluxed for 20 minutes and then 20 ml of a buffer pH 4.6 containing 2.2 g of dichlorodicyano-p-quinone was added. The mixture was allowed to stand at room temperature for 15 hours and then was treated as described in Example 1 to obtain the rifamycin P. Yield 2.8 g of the title product. The mixture was refluxed for 20 minutes was added was treated

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

Procedure: To a solution of 7 g of rifamycin S in 200 ml of methanol a mixture was added containing 1.8 g of the hydrochloride of cysteine methyl ester and 1.53 g of triethylamine. The mixture was refluxed for 20 minutes and then 20 ml of a buffer pH 4.6 containing 2.2 g of dichlorodicyano-p-quinone was added. The mixture was allowed to stand at room temperature for 15 hours and then was treated as described in Example 1 to obtain the rifamycin P. Yield 2.8 g of the title product. The mixture was refluxed for 20 minutes was added was treated

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

Procedure: A solution of L-cysteine methyl ester (1.71 g) and 5-formyl-2(S)-phthalimidopentanoic acid (3.49 g) in 120 ml of tetrahydrofuran was stirred under nitrogen for 2.5 hours and then taken to dryness to yield a white foam. This residue was dissolved in 250 ml of chloroform and washed with water (2×30 ml). The combined aqueous layers were back extracted with chloroform (2×30 ml). The organic layers were dried (Na2SO4) and then concentrated in vacuo to give a white foam, 4.83 g. Tlc on silica [4:1 Ethyl acetate:acetic acid] indicated a major spot at Rf =0.72. Exact mass measurement showed a molecular ion at 392.1024 (calcd. 392.1041). 'H NMR spectrum (CDCl3) showed a multiplet at δ7.72 (4H) and a singlet at δ3.78(3H). to yield a white foam washed with water (2×30 ml) The combined aqueous layers were back extracted with chloroform (2×30 ml) The organic layers were dried (Na2SO4) concentrated in vacuo to give a white foam, 4.83 g

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

Procedure: A solution of L-cysteine methyl ester (1.71 g) and 5-formyl-2(S)-phthalimidopentanoic acid (3.49 g) in 120 ml of tetrahydrofuran was stirred under nitrogen for 2.5 hours and then taken to dryness to yield a white foam. This residue was dissolved in 250 ml of chloroform and washed with water (2×30 ml). The combined aqueous layers were back extracted with chloroform (2×30 ml). The organic layers were dried (Na2SO4) and then concentrated in vacuo to give a white foam, 4.83 g. Tlc on silica [4:1 Ethyl acetate:acetic acid] indicated a major spot at Rf =0.72. Exact mass measurement showed a molecular ion at 392.1024 (calcd. 392.1041). 'H NMR spectrum (CDCl3) showed a multiplet at δ7.72 (4H) and a singlet at δ3.78(3H). to yield a white foam washed with water (2×30 ml) The combined aqueous layers were back extracted with chloroform (2×30 ml) The organic layers were dried (Na2SO4) concentrated in vacuo to give a white foam, 4.83 g

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL round bottomed flask at 0° C. is added L-Cysteine methyl ester (1.38 g, 10.2 mmols) in 60 mL of 7M NH3/MeOH. Neat farnesyl bromide (1b) (1.00 g 3.52 mmols) is then added and the solution is stirred at 0° C. for four hours. The reaction mixture is partitioned between ether and water and extracted 3× with ether, extracts are combined, dried over MgSO4 filtered and evaporated. Purification by flash chromatography (1% MeOH:CHCl3) yields 881 mg (74%) of a clear oil. Rf=0.22 in 5% MeOH in CHCl3. 1H NMR (CDCl3, 400 MHz): 5.24 (t, 1H, J=8 Hz), 5.10 (m, 2H), 3.75 (s, 3H), 3.64 (q, 1H), 3.10-3.25 (m, 2H), 2.86-2.91 (2d, 1H), 2.65-2.71 (2d, 1H), 2.04-2.10 (m, 6H), 2.04(m, 6H) 2.0 (t, 2H), 1.69 (s, 3H), 1.68 (s. 3H), 1.60 (s, 6H); 13C NMR (CDCl3, 50 MHz) 174.93, 139.91, 135.71, 131.62, 124.69, 124.11, 120.35, 54.64, 52.35, 39.93, 36.77, 30.15, 26.98, 26.67, 25.86, 17.86, 16.33, 16.21 MS: (ESI, +) (M−H+) 340 The reaction mixture is partitioned between ether and water extracted 3× with ether, extracts dried over MgSO4 filtered evaporated Purification by flash chromatography (1% MeOH:CHCl3)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL round bottomed flask at 0° C. is added L-Cysteine methyl ester (1.38 g, 10.2 mmols) in 60 mL of 7M NH3/MeOH. Neat farnesyl bromide (1b) (1.00 g 3.52 mmols) is then added and the solution is stirred at 0° C. for four hours. The reaction mixture is partitioned between ether and water and extracted 3× with ether, extracts are combined, dried over MgSO4 filtered and evaporated. Purification by flash chromatography (1% MeOH:CHCl3) yields 881 mg (74%) of a clear oil. Rf=0.22 in 5% MeOH in CHCl3. 1H NMR (CDCl3, 400 MHz): 5.24 (t, 1H, J=8 Hz), 5.10 (m, 2H), 3.75 (s, 3H), 3.64 (q, 1H), 3.10-3.25 (m, 2H), 2.86-2.91 (2d, 1H), 2.65-2.71 (2d, 1H), 2.04-2.10 (m, 6H), 2.04(m, 6H) 2.0 (t, 2H), 1.69 (s, 3H), 1.68 (s. 3H), 1.60 (s, 6H); 13C NMR (CDCl3, 50 MHz) 174.93, 139.91, 135.71, 131.62, 124.69, 124.11, 120.35, 54.64, 52.35, 39.93, 36.77, 30.15, 26.98, 26.67, 25.86, 17.86, 16.33, 16.21 MS: (ESI, +) (M−H+) 340 The reaction mixture is partitioned between ether and water extracted 3× with ether, extracts dried over MgSO4 filtered evaporated Purification by flash chromatography (1% MeOH:CHCl3)

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

Procedure: A solution of L-cysteine methyl ester (1.71 g) and 5-formyl-2(S)-phthalimidopentanoic acid (3.49 g) in 120 ml of tetrahydrofuran was stirred under nitrogen for 2.5 hours and then taken to dryness to yield a white foam. This residue was dissolved in 250 ml of chloroform and washed with water (2×30 ml). The combined aqueous layers were back extracted with chloroform (2×30 ml). The organic layers were dried (Na2SO4) and then concentrated in vacuo to give a white foam, 4.83 g. Tlc on silica [4:1 Ethyl acetate:acetic acid] indicated a major spot at Rf =0.72. Exact mass measurement showed a molecular ion at 392.1024 (calcd. 392.1041). 'H NMR spectrum (CDCl3) showed a multiplet at δ7.72 (4H) and a singlet at δ3.78(3H). to yield a white foam washed with water (2×30 ml) The combined aqueous layers were back extracted with chloroform (2×30 ml) The organic layers were dried (Na2SO4) concentrated in vacuo to give a white foam, 4.83 g

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

Procedure: To a solution of 7 g of rifamycin S in 200 ml of methanol a mixture was added containing 1.8 g of the hydrochloride of cysteine methyl ester and 1.53 g of triethylamine. The mixture was refluxed for 20 minutes and then 20 ml of a buffer pH 4.6 containing 2.2 g of dichlorodicyano-p-quinone was added. The mixture was allowed to stand at room temperature for 15 hours and then was treated as described in Example 1 to obtain the rifamycin P. Yield 2.8 g of the title product. The mixture was refluxed for 20 minutes was added was treated

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

Procedure: A solution of L-cysteine methyl ester (1.71 g) and 5-formyl-2(S)-phthalimidopentanoic acid (3.49 g) in 120 ml of tetrahydrofuran was stirred under nitrogen for 2.5 hours and then taken to dryness to yield a white foam. This residue was dissolved in 250 ml of chloroform and washed with water (2×30 ml). The combined aqueous layers were back extracted with chloroform (2×30 ml). The organic layers were dried (Na2SO4) and then concentrated in vacuo to give a white foam, 4.83 g. Tlc on silica [4:1 Ethyl acetate:acetic acid] indicated a major spot at Rf =0.72. Exact mass measurement showed a molecular ion at 392.1024 (calcd. 392.1041). 'H NMR spectrum (CDCl3) showed a multiplet at δ7.72 (4H) and a singlet at δ3.78(3H). to yield a white foam washed with water (2×30 ml) The combined aqueous layers were back extracted with chloroform (2×30 ml) The organic layers were dried (Na2SO4) concentrated in vacuo to give a white foam, 4.83 g

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a 100 mL round bottomed flask at 0° C. is added L-Cysteine methyl ester (1.38 g, 10.2 mmols) in 60 mL of 7M NH3/MeOH. Neat farnesyl bromide (1b) (1.00 g 3.52 mmols) is then added and the solution is stirred at 0° C. for four hours. The reaction mixture is partitioned between ether and water and extracted 3× with ether, extracts are combined, dried over MgSO4 filtered and evaporated. Purification by flash chromatography (1% MeOH:CHCl3) yields 881 mg (74%) of a clear oil. Rf=0.22 in 5% MeOH in CHCl3. 1H NMR (CDCl3, 400 MHz): 5.24 (t, 1H, J=8 Hz), 5.10 (m, 2H), 3.75 (s, 3H), 3.64 (q, 1H), 3.10-3.25 (m, 2H), 2.86-2.91 (2d, 1H), 2.65-2.71 (2d, 1H), 2.04-2.10 (m, 6H), 2.04(m, 6H) 2.0 (t, 2H), 1.69 (s, 3H), 1.68 (s. 3H), 1.60 (s, 6H); 13C NMR (CDCl3, 50 MHz) 174.93, 139.91, 135.71, 131.62, 124.69, 124.11, 120.35, 54.64, 52.35, 39.93, 36.77, 30.15, 26.98, 26.67, 25.86, 17.86, 16.33, 16.21 MS: (ESI, +) (M−H+) 340 The reaction mixture is partitioned between ether and water extracted 3× with ether, extracts dried over MgSO4 filtered evaporated Purification by flash chromatography (1% MeOH:CHCl3)