Name: 52-67-5|(S)-2-Amino-3-mercapto-3-methylbutanoic acid|98%
Brand: Ambeed
SKU: A101389
Price: 5.0 USD
Availability: InStock
Rating: 97 (25 reviews)

1
[ 67-56-1 ]
[ 52-67-5 ]
[ 29913-83-5 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; for 60h;Heating / reflux;	This set of experiments utilized both <strong>[52-67-5]D-penicillamine</strong>, and its more lipophilic derivative, <strong>[52-67-5]D-penicillamine</strong> methyl ester. To make the derivative, 18 ml of SOCl2 in 75 ml of MeOH which had been stored at -10 C. was stirred, and varying amounts of <strong>[52-67-5]D-penicillamine</strong> (15 g, 100.5 mmol) were added. Stirring continued while the mixture reached room temperature. The mixture was refluxed for 60 hours, and solvent was then evaporated, leaving a crude product (15.2 g, 93.3 mmol), which was dissolved in methanol, then crystallized with addition of ether. Crystallized product was collected, and dried under a vacuum, leaving 7.6 g of pure product. Its structure was confirmed by 'H-NMR and mass spectrometry. The m/z calculated for C6H14O2NS was 164.1 [M+H]+, observed 164.1. In each case, 10 mM of the test compound was used, over 24 hours, on human A431 cells, and apoptosis was measured as described, supra. In FIG. 3, ?D-P? refers to <strong>[52-67-5]D-penicillamine</strong>, while ?D-P-OCH3? is the methyl ester. A stronger apoptotic effect was seen with the ester.

Reference： [1]Journal of Pharmacology and Experimental Therapeutics,2006,vol. 316,p. 805 - 814
[2]Patent: US2491523,1946,
[3]Journal of medicinal chemistry,1971,vol. 14,p. 868 - 872
[4]Journal of Chemical and Engineering Data,1984,vol. 29,p. 351 - 354
[5]Patent: US2005/197400,2005,A1 .Location in patent: Page/Page column 2

2
[ 50-00-0 ]
[ 52-67-5 ]
[ 22916-26-3 ]

Yield	Reaction Conditions	Operation in experiment
96%	In ethanol; water; at 20℃; for 18h;	[00063] Procedure:To a stirred solution of <strong>[52-67-5]D-penicillamine</strong> (5.0 g, 0.033 mole; 1.0 eq) in ethanol (30 mL,6 vol) & water (10 mL, 2 vol) mixture was added paraformaldehyde (2.41 gm, 0.026 mole, 0.9 eq) at room temperature and the reaction mixture was stirred for 18 h at room temperature. On completion of the reaction (monitored by TLC), the reaction mixture was filter and obtained solid was washed with fresh ethanol (20 mL). The solid mass was suck dried under vacuum to get 5.2 gm compound as a white solid . Yield%: 5.2 g (96 %). [00064] Analytical Data: 1H-NMR (D20): delta 1.45 (s, 3H, -CH3), 1.69 (s, 3H, -CH3), 4.01 (s, 1H, -CHCOOH), 4.44 -4.46 (d, 1H, J=9.76 Hz), 4.51-4.53 (d, 1H, J-9.76 Hz).

Reference： [1]Patent: WO2017/60914,2017,A2 .Location in patent: Paragraph 00061-00064
[2]Journal of Medicinal Chemistry,1992,vol. 35,p. 2582 - 2591
[3]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 5933 - 5949
[4]Canadian Journal of Chemistry,1986,vol. 64,p. 1215 - 1219
[5]Chemistry of Penicillin,
[6]Journal of Medicinal Chemistry,1984,vol. 27,p. 591 - 596

3
[ 52-67-5 ]
[ 2032-34-0 ]
(2Ξ,4S)-2-cyanomethyl-5,5-dimethyl-thiazolidine-4-carboxylic acid ; hydrochloride [ No CAS ]

Reference： [1]Chemistry of Penicillin,

4
[ 52-67-5 ]
[ 20902-45-8 ]

Yield	Reaction Conditions	Operation in experiment
	With dihydrogen peroxide; In water;pH 8;	d-Penicillamine disulfide (5) was synthesized in situ by dissolving 0.10 g (0.67 mmol) d-penicillamine (1) into a 5% H2O2 aqueous solution and adjusting the pH to 8. After stirring overnight the aqueous solution was used directly for NMR measurements. 1H NMR (600 MHz, H2O:D2O, 95:5, v/v) delta (ppm) 1.44 (3H, s, betaCH3), 1.55 (3H, s, betaCH3), 4.01 (1H, s, alphaH); HRMS m/z [M+H]+ Calc 297.0943 Found 297.1017.
	With dihydrogen peroxide; In water;pH 8;	D-Penicillamine disulfide (5) was synthesized in situ by dissolv-ing 0.10 g (0.67 mmol) d-penicillamine (1) into a 5% H2O2aqueoussolution and adjusting the pH to 8. After stirring overnight the aque-ous solution was used directly for NMR measurements

Reference： [1]European Journal of Organic Chemistry,2010,p. 2661 - 2665
[2]Chemistry of Penicillin,
[3]Canadian Journal of Chemistry,1969,vol. 47,p. 1029 - 1036
[4]Journal of Mass Spectrometry,2006,vol. 41,p. 1578 - 1593
[5]Heteroatom Chemistry,2007,vol. 18,p. 467 - 471
[6]Chemical Physics Letters,2014,vol. 610-611,p. 62 - 69
[7]Chemical Physics Letters,2015,vol. 610-611,p. 62 - 69
[8]Journal of Coordination Chemistry,2017,vol. 70,p. 1723 - 1738

5
[ 52-67-5 ]
[ 100-52-7 ]
[ 280108-25-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	In ethanol; water; at 20℃;Inert atmosphere; Schlenk technique;	In a 100 mL round bottom flask 2.00 g (13.40 mmol, 1.00 eq) <strong>[52-67-5]D-penicillamine</strong> were dissolved in 40 mL H2O:EtOH (10/3). 1.37 mL (1.42 g, 13.40 mmol, 1.00 eq) benzaldehyde were added to this clear colorless solution and the mixture was stirred at rt overnight. Full conversion was detected via TLC and the product was collected by filtration and washed with ice cold Et2O (20 mL). The product was dried in vacuo, giving a white powder (2.63 g, 11.1 mmol, 83%) as crude product. The crude product was used without further purification in the next step. TLC: Rf = 0.28 (DCM/MeOH/NH3 = 3/1/ 0.01); m.p. = 165 C;

Reference： [1]Tetrahedron,2020
[2]Chemistry of Penicillin,
[3]Chemical Communications (London),1968,p. 11 - 12
[4]Chemical and Pharmaceutical Bulletin,1990,vol. 38,p. 936 - 941

6
[ 52-67-5 ]
[ 33142-21-1 ]
(2Ξ,4S)-2-((Ξ)-ethoxycarbonyl-chloro-methyl)-5,5-dimethyl-thiazolidine-4-carboxylic acid [ No CAS ]

Reference： [1]Chemistry of Penicillin,

7
[ 67-56-1 ]
[ 52-67-5 ]
[ 34297-27-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With hydrogenchloride; at 20℃;	d-Penicillamine methyl ester hydrochloride (2) was synthesized by dissolving 0.10 g (0.67 mmol) d-penicillamine (1) in 5 ml methanol and bubbling dry HCl gas into the solution for 15 min at room temperature [19] . After stirring overnight at room temperature the reaction mixture was evaporated in vacuo to yield a white solid (0.13 g, 98%). Mp: 187-188 C; 1H NMR (600 MHz, H2O:D2O, 95:5, v/v) delta (ppm) 1.42 (3H, s, betaCH3), 1.45 (3H, s, betaCH3), 3.68 (1H, s, alphaH), 3.79 (3H, s, OCH3); HRMS m/z [M+H]+ Calc 164.0745 Found 164.0724.
98%	With hydrogenchloride; at 20℃;	General procedure: D-Penicillamine methyl ester hydrochloride (2) was synthe-sized by dissolving 0.10 g (0.67 mmol) d-penicillamine (1) in 5 mlmethanol and bubbling dry HCl gas into the solution for 15 min atroom temperature [19]. After stirring overnight at room tempera-ture the reaction mixture was evaporated in vacuo to yield a whitesolid (0.13 g, 98%)
91%	With thionyl chloride; at 0 - 20℃; for 48.5h;	[00050] Procedure: To a stirred solution of D-penicillarnine (5.0 g, 0.033 mole; 1.0 eq) in methanol (100 mL; LR grade) was added thionyl chloride ( 40 gm, 0.33 mole, 10 eq) at 0 C over 30 min and the reaction mixture was stirred for 48 h at room temperature. On completion of the reaction (monitored by TLC), the reaction mixture evaporate under reduced pressure to get white sticky solid mass. The residue was triturated with diethyl ether (2 x 100 mL) and dried under vacuum to get 6.1 gm compound as a white solid. Yield%: 6.1 g (91%).

Reference： [1]Chemical Physics Letters,2014,vol. 610-611,p. 62 - 69
[2]Chemical Physics Letters,2015,vol. 610-611,p. 62 - 69
[3]Patent: WO2017/60914,2017,A2 .Location in patent: Paragraph 00048-00050
[4]Journal of the Chemical Society, Dalton Transactions,1984,p. 1333 - 1342
[5]Angewandte Chemie - International Edition,2008,vol. 47,p. 3784 - 3786
[6]Tetrahedron,2016,vol. 72,p. 5923 - 5927

8
[ 52-67-5 ]
[ 70-34-8 ]
1-Fluoro-2,4-dinitro-benzene; compound with (S)-2-amino-3-mercapto-3-methyl-butyric acid [ No CAS ]

Reference： [1]Pharmazie,1985,vol. 40,p. 581 - 582

9
[ 52-67-5 ]
[ 625-51-4 ]
[ 111491-50-0 ]

Reference： [1]Canadian Journal of Chemistry,1987,vol. 65,p. 878 - 883

10
[ 113-98-4 ]
[ 95-54-5 ]
[ 51-17-2 ]
[ 621-72-7 ]
[ 52-67-5 ]
[ 121766-69-6 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1989,vol. 37,p. 1609 - 1611
[2]Chemical and Pharmaceutical Bulletin,1989,vol. 37,p. 1609 - 1611

11
[ 113-98-4 ]
[ 95-54-5 ]
[ 51-17-2 ]
[ 621-72-7 ]
[ 52-67-5 ]
[ 124827-17-4 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1989,vol. 37,p. 1609 - 1611

12
[ 113-98-4 ]
[ 95-54-5 ]
[ 51-17-2 ]
[ 621-72-7 ]
[ 52-67-5 ]
[ 124827-18-5 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1989,vol. 37,p. 1609 - 1611

13
[ 113-98-4 ]
[ 150-61-8 ]
[ 52-67-5 ]
[ 59281-89-9 ]
[ 55055-34-0 ]
6,7-dihydro-6H-3-phenylacetylamino-1,5-diazepin-2-one [ No CAS ]

Reference： [1]Heterocycles,1988,vol. 27,p. 2815 - 2824

14
[ 113-98-4 ]
[ 150-61-8 ]
[ 52-67-5 ]
[ 55055-34-0 ]
N-(2-anilinoethyl)-2-phenylacetamidoacetanilide [ No CAS ]
6,7-dihydro-6H-3-phenylacetylamino-1,5-diazepin-2-one [ No CAS ]

Reference： [1]Heterocycles,1988,vol. 27,p. 2815 - 2824

15
[ 52-67-5 ]
[ 939-69-5 ]
[ 73918-30-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In water; at 20℃; for 3h;	General procedure: The hydroxy- or methoxycarbonitrile derivative (1 eq) was added to the cysteine derivative (1.05 eq) and sodium carbonate (3 eq) in 5 ml water. The mixture was stirred at room temperature for three hours before addition of dilute HCl (1 M) to pH ? 3.5 ? 4.0. The product was isolated by extraction with diethyl ether, washed by water, followed by evaporation

Reference： [1]Journal of the American Chemical Society,2002,vol. 124,p. 2112 - 2113
[2]European Journal of Medicinal Chemistry,2015,vol. 94,p. 140 - 148

16
[ 52-67-5 ]
[ 2082-59-9 ]
[ 6106-41-8 ]
N-valeryl-D-penicillamine [ No CAS ]

Reference： [1]European Journal of Pharmacology,2000,vol. 408,p. 335 - 343

17
[ 132-98-9 ]
[ 52-67-5 ]

Reference： [1]Heterocycles,1988,vol. 27,p. 2815 - 2824
[2]Heterocycles,1988,vol. 27,p. 2815 - 2824

18
[ 113-98-4 ]
[ 52-67-5 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[2]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[3]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[4]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[5]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[6]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[7]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[8]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[9]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[10]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[11]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[12]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[13]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[14]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962
[15]Chemical and Pharmaceutical Bulletin,1988,vol. 36,p. 1957 - 1962

19
[ 52-67-5 ]
[ 2280-27-5 ]

Reference： [1]Canadian Journal of Chemistry,1969,vol. 47,p. 1029 - 1036

20
[ 52-67-5 ]
[ 108-24-7 ]
[ 79913-44-3 ]

Yield	Reaction Conditions	Operation in experiment
89%		(b) (2S,4S)-3-Acetyl-5,5-dimethyl-2-phenyl-4-thiazolidinecarboxylic acid (Reference compound No. 5-1b) A solution of benzaldehyde (102 ml, 1.01 mol) in ethanol (300 ml) was added to a solution of <strong>[52-67-5]D-penicillamine</strong> (150 g, 1.01 mol) in water (900 ml) at room temperature. The mixture was stirred at room temperature for 15 minutes and under ice-cooling for 1.5 hours, and then the precipitated crystals were filtered off and dried. Acetic anhydride (480 ml, 5.05 mol) was added dropwise to a solution of the obtained crystals in water (700 ml) at 60C over 15 minutes. The mixture was stirred at the temperature for 15 minutes, then at room temperature for 15 minutes and under ice-cooling for 1.5 hours, and the precipitated crystals were filtered off and dried to give 252.3 g (89%) of the target compound. IR (neat) 3392, 2920, 1730, 1618, 1411, 1196, 1178, 732 cm-1

Reference： [1]Patent: EP1496053,2005,A1 .Location in patent: Page 32

21
[ 52-67-5 ]
[ 61040-78-6 ]
(2S)-2-Amino-3-methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In dichloromethane;	44a. (2S)-2-Amino-3-methyl-3-[(2,4,6-trimethoxyphenyl)methylthio]butanoic acid A suspension of (2S)-2-amino-3-methyl-3-sulfanylbutanoic acid (5.0 g, 703 mmol) in CH2Cl2 (150 mL) was cooled to 0 C. Trifluoroacetic acid (54 mL, 703 mmol) was added dropwise over a period of 5 min. 2,4,6-trimethoxybenzyl alcohol (6.64 g, 34 mmol) in CH2Cl2 (137 mL) was added dropwise at 0 C. with stirring. The stirring was continued for 1 hour at 0 C. and 2 hours at room temperature, the solvent removed in vaciio and the residue was dried under high vacuum for 3 hours. The crude red solid was recrystallized from 1:1:1 CH2Cl2:MeOH:EtOAc to give the title compound 10.5 g (95 %) as a white solid which was used for the next step without further purification. 1H NMR (300 MHz, CDCl3) delta 6.10 (s, 2H), 3.84 (s, 6H), 3.76 (s, 3H), 3.40-4.10 (mult, 3H), 1.69 (s, 3H), 1.23 (s, 3H); mass spectrum (API-TIS) m/z 330 (M+H).

Reference： [1]Patent: US6297260,2001,B1

22
[ 52-67-5 ]
[ 24424-99-5 ]
[ 106-95-6 ]
[ 292638-85-8 ]
[ 214353-96-5 ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium; 1,8-diazabicyclo[5.4.0]undec-7-ene; triethylamine; In tetrahydrofuran; methanol; hexane;	(i) N-(tert-Butoxycarbonyl)--S--[2-(methoxycarbonyl)ethyl]-<strong>[52-67-5]D-penicillamine</strong> allyl ester To a suspension of <strong>[52-67-5]D-penicillamine</strong> (10.0 g., 67.02 mmol) in methanol (100 mL) at 0 C. was added 14.5 mL (67 mmol) of a 25 wt % solution of sodium in methanol dropwise. After 15 minutes, methyl acrylate (6.35 mL, 70 mmol) was added dropwise, and the solution was allowed to warm to room temperature overnight. Removal of the solvent by rotary evaporation provided a white solid, which was dissolved in 50% aqueous (100 mL). To the resulting solution was added triethylamine (14 mL, 100 mmol), followed by di-t-butyldicarbonate (16.05 g., 73.6 mmol). After stirring for 12 hours at room temperature, the mixture was concentrated to remove most of the THF, and the resulting aqueous solution was acidified with acetic acid and then extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated. The residue was dissolved in THF (75 mL) and DBU (10.2 mL, 68.2 mmol) added, followed by addition of allyl bromide (6.14 mL, 71.0 mmol). The solution was stirred at room temperature for 5 hours, and then the solvent was removed by concentration under reduced pressure. The residue was purified on silica gel, eluding with 5% to 10% to 20% ethyl acetate in hexane, to provide N-(tert-butoxycarbonyl)--S--[2-(methoxycarbonyl)ethyl]-<strong>[52-67-5]D-penicillamine</strong> allyl ester as a colorless oil in 44% overall yield: 1 H--NMR (CDCl3) delta 1.36 (s, 3H), 1.38 (s, 3H), 1.44 (s, 9H), 2.52-2.57 (t, 2H, J=8 Hz), 2.75-2.82 (m, 2H), 3.69 (s, 3H), 4.32-4.35 (m, 1H), 4.62-4.64 (m, 2H), 5.27-5.39 (m, 3H), 5.85-6.00 (m, 1H); FAB HRMS: expected (M+Cs)=508.0770, found (M+Cs)=508.0750.

Reference： [1]Patent: US5985900,1999,A

23
[ 52-67-5 ]
[ 19276-03-0 ]
[ 192329-91-2 ]
[ 214353-29-4 ]

Yield	Reaction Conditions	Operation in experiment
52%	With acetic acid; 1,8-diazabicyclo[5.4.0]undec-7-ene; N-ethyl-N,N-diisopropylamine; In methanol; diethyl ether; N,N-dimethyl-formamide;	Example 3(a) S--[(1-Benzyl-1H-imidazol-2-yl)methyl]--N--[4-(4-fluorophenoxy) benzenesulfonyl]-<strong>[52-67-5]D-penicillamine</strong> {III-A, W=(1-Benzyl-1H-imidazol-2-yl)CH2 S, Z=F} To a suspension of <strong>[52-67-5]D-penicillamine</strong> (0.500 g, 3.35 mmol) in DMF (7 mL) was added diisopropylethylamine (0.70 mL., 4.0 mmol), followed by dimethylthexylsilyl chloride (0.725 mL, 3.68 mmol). After 2.5 hours at room temperature, the solution was cooled to 0 C., and DBU (1.59 mL, 10.7 mmol) was added, followed by 2-chloromethyl-1-benzyl-1H-imidazole hydrochloride (0.977 g., 4.02 mmol, Maybridge). The solution was allowed to warm to room temperature. After 3 hours, the solution was recooled to 0 C., diisopropylethylamine (0.70 mL., 4.0 mmol) was added, followed by 4-(4-fluorophenoxy)benzenesulfonyl chloride (1.01 g., 4.00 mmol). The solution was allowed to slowly warm to room temperature, stirred for 5 h, and then partitioned between brine and ethyl acetate. The organic layer was washed with brine, filtered through celite, and concentrated. The residue was dissolved in methanol (50 mL), and treated with acetic acid (0.400 mL). After 2 hours at room temperature, the solution was concentrated, and the residue was purified on silica, eluding with 5% methanol/dichloromethane. Trituration of the residue with 25% diethyl ether/hexane gave S--[(1-benzyl-1H-imidazol-2-yl)methyl]--N--[4-(4-fluorophenoxy)benzenesulfonyl]-<strong>[52-67-5]D-penicillamine</strong> as a white solid in 52% yield: mp 172-173 C.; 1 H--NMR (CDCl3) delta 1.29 (s, 3H), 1.44 (s, 3H), 3.75-4.02 (m, 3H), 5.29 (s, 2H), 6.95-7.65 (m, 15H). Anal calcd. for C28 H28 FN3 O5 S2: C, 59.03; H, 4.95; N, 7.38; S, 11.26. Found: C, 58.77; H, 4.97; N, 7.33; S, 11.07.

Reference： [1]Patent: US5985900,1999,A

24
[ 908094-01-9 ]
[ 1138-56-3 ]
[ 52-67-5 ]
[ 598-18-5 ]
Methyl N-[(4-butoxyphenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane; methanol; sodium hydroxide; diethyl ether; ethanol; hexane; water	6.a Preparation of N-Hydroxy-4-[(4-butoxyphenyl)sulfonyl]-2,2-dimethyl-thiazepine-3-carboxamide STR15 6a. Methyl N-[(4-butoxyphenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine: D-Penicillamine (2.5 g, 16.7 mmol) in 2N NaOH (18 mL, 1.35 equiv) is stirred at 0° C. under an Argon atmosphere. A solution of 2-bromopropanol (3.24 g, 23.4 mmol, 1.4 equiv) in ethanol (20 mL) is slowly added dropwise at 0° C. The resulting solution is stirred overnight at room temperature and then the mixture is acidified to pH ~6 with 1N HCl. The solvent is removed under reduced pressure to leave a thick oil. The penicillamine adduct is then dissolved in dioxane (30 mL) and water (30 mL) and stirred at room temperature. Triethylamine (7.0 mL, 50.1 mmol, 3 equiv) is then added to the reaction mixture followed by 4-n-butoxyphenylsulfonyl chloride (5.0 g, 20.1 mmol). The resulting homogeneous solution is stirred at room temperature for 18 hours and then acidified to pH ~2 with 1N HCl. The solution is poured into water and extracted with methylene chloride. The organic extracts are dried (MgSO4) and concentrated to an oil under reduced pressure. The resulting oil is diluted in methanol (30 mL) and enough diazomethane in diethyl ether is added to form a yellow solution. The mixture is concentrated under reduced pressure to leave a colorless oil. Purification of the resulting methyl ester is accomplished by chromatography on silica gel using 3/2 hexane/EtOAc as the eluent. The desired product is obtained as a clear, colorless oil. MS (ESI): 434 (M+ +H), 451 (M+ +NH4)

Reference： [1]Current Patent Assignee: PROCTER & GAMBLE CO - US6166005, 2000, A

25
[ 908094-01-9 ]
[ 52-67-5 ]
[ 598-18-5 ]
[ 139937-37-4 ]
Methyl N-[(2-methyl-4-bromophenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane; methanol; sodium hydroxide; diethyl ether; ethanol; hexane; water	8.a Preparation of N-Hydroxy-4-[(2-methyl-4-bromophenyl)sulfonyl]-2,2-dimethyl-thiazepine-3-carboxamide STR17 8a. Methyl N-[(2-methyl-4-bromophenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine: D-Penicillamine (3.0 g, 20.1 mmol) in 2N NaOH (18 mL, 1.35 equiv) is stirred at 0° C. under an Argon atmosphere. A solution of 2-bromopropanol (3.91 g, 28.1 mmol, 1.4 equiv) in ethanol (20 mL) is slowly added dropwise at 0° C. The resulting solution is stirred overnight at room temperature and then the mixture is acidified to pH ~6 with 1N HCl. The solvent is removed under reduced pressure to leave a thick oil. The penicillamine adduct is then dissolved in dioxane (30 mL) and water (30 mL) and stirred at room temperature. Triethylamine (8.3 mL, 60.0 mmol, 3 equiv) is then added to the reaction mixture followed by 2-methyl-4-bromophenylsulfonyl chloride (6.5 g, 24.1 mmol). The resulting homogeneous solution is stirred at room temperature for 18 hours and then acidified to pH ~2 with 1N HCl. The solution is poured into water and extracted with methylene chloride. The organic extracts are dried (MgSO4) and concentrated to an oil under reduced pressure. The resulting oil is diluted in methanol (30 mL) and enough diazomethane in diethyl ether is added to form a yellow solution. The mixture is concentrated under reduced pressure to leave a colorless oil. Purification of the resulting methyl ester is accomplished by chromatography on silica gel using 1/1 hexane/EtOAc as the eluent. The desired product is obtained as a clear, colorless oil. MS (ESI): 456, 458 (M+ +H), 473, 475 (M+ +NH4)

Reference： [1]Current Patent Assignee: PROCTER & GAMBLE CO - US6166005, 2000, A

26
[ 908094-01-9 ]
[ 52-67-5 ]
[ 598-18-5 ]
[ 98-68-0 ]
Methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane; methanol; sodium hydroxide; diethyl ether; ethanol; hexane; water	1.a Preparation of N-Hydroxy-2,2-dimethyl-S,S-dioxo-4-[(4-methoxyphenyl)sulfonyl]thiazepine-3(S)-carboxamide STR10 1a. Methyl N-[(4-methoxyphenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine: D-Penicillamine (29.8 g, 0.2 mol) in 2N NaOH (135 mL, 0.27 mol, 1.35 equiv) is stirred at 0° C. under an Argon atmosphere. A solution of 2-bromopropanol (36.1 g, 0.26 mol, 1.3 equiv) in ethanol (200 mL) is slowly added dropwise at 0° C. The resulting solution is stirred overnight at room temperature and then the mixture is acidified to pH ~6 with 1N HCl. The solvent is removed under reduced pressure to leave a thick oil. The penicillamine adduct is then dissolved in dioxane (200 mL) and water (200 mL) and stirred at room temperature. Triethylamine (58.6 g, 0.58 mol, 3 equiv) is then added to the reaction mixture followed by 4-methoxyphenylsulfonyl chloride (40.0 g, 0.193 mol). The resulting homogeneous solution is stirred at room temperature for 18 hours and then acidified to pH ~2 with 1N HCl. The solution is poured into water and extracted with methylene chloride. The organic extracts were dried (MgSO4) and concentrated to an oil under reduced pressure. The resulting oil is diluted in methanol (30 mL) and enough diazomethane in diethyl ether is added to form a yellow solution. The mixture is concentrated under reduced pressure to leave a colorless oil. Purification of the resulting methyl ester is accomplished by chromatography on silica gel using 1/1 hexane/EtOAc as the eluent. The desired product is obtained as a clear, colorless oil.

Reference： [1]Current Patent Assignee: PROCTER & GAMBLE CO - US6166005, 2000, A

27
[ 908094-01-9 ]
[ 52-67-5 ]
[ 598-18-5 ]
[ 98-58-8 ]
Methyl N-[(4-bromophenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In 1,4-dioxane; methanol; sodium hydroxide; diethyl ether; ethanol; water; ethyl acetate	4.a Preparation of N-Hydroxy-S,S-dioxo-2,2-dimethyl-4-[(4-bromophenyl)sulfonyl]thiazepine-3(S)-carboxamide STR13 4a. Methyl N-[(4-bromophenyl)sulfonyl]-S-(2-hydroxypropyl)-D-penicillamine: D-Penicillamine (20.9 g, 134.0 mmol) in 2N NaOH (88 mL, 174.2 mmol, 1.35 equiv) is stirred at 0° C. under an Argon atmosphere. A solution of 2-bromopropanol (26.0 g, 187.7 mmol, 1.3 equiv) in ethanol (150 mL) is slowly added dropwise at 0° C. The resulting solution is stirred overnight at room temperature and then the mixture is acidified to pH ~6 with 1N HCl. The solvent is removed under reduced pressure to leave a thick oil. The penicillamine adduct is then dissolved in dioxane (150 mL) and water (150 mL) and stirred at room temperature. Triethylamine (40.6 g, 402 mmol, 3 equiv) is then added to the reaction mixture followed by 4-bromophenylsulfonyl chloride (41.1 g, 160.8 mmol). The resulting homogeneous solution is stirred at room temperature for 18 hours and then acidified to pH ~2 with 1N HCl. The solution is poured into water and extracted with methylene chloride. The organic extracts were dried (MgSO4) and concentrated to an oil under reduced pressure. The resulting oil is diluted in methanol (30 mL) and enough diazomethane in diethyl ether is added to form a yellow solution. The mixture is concentrated under reduced pressure to leave a colorless oil. Purification of the resulting methyl ester is accomplished by chromatography on silica gel using 40% ethyl acetate/60% hexane as the eluent. The desired product is obtained as a clear, colorless oil. MS (ESI): 440, 442 (M+ +H), 457, 459 (M+ +NH4)

Reference： [1]Current Patent Assignee: PROCTER & GAMBLE CO - US6166005, 2000, A

28
[ 52-67-5 ]
[ 24424-99-5 ]
[ 119222-62-7 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sodium hydroxide; In ethyl acetate; tert-butyl alcohol;	(A) N-(t-Butoxycarbonyl)-3-mercapto-D-valine. A mixture of <strong>[52-67-5]D-penicillamine</strong> (5.00 g, 33.51 mmol), t-butyl alcohol (100 mL), 2N aqueous sodium hydroxide (25 mL) and di-t-butyl dicarbonate (8.05 g, 36.86 mmol) is stirred at room for about 16 hours. The reaction mixture is diluted with 800 mL of ethyl acetate, and washed with 200 mL of aqueous 3N sodium bisulfate, dried over magnesium sulfate and then concentrated to give 8.21 g of the title compound as a white solid, 98% yield, m.p. 120 C. (decomposes). 1 H NMR (300 MHz, CDCl3): 5.47 (br d, J=9.3, 1H), 4.30 (d, J=9.3, 1H), 2.02 (s, 1H), 1.54 (s, 3H), 1.44 (s, 9H), 1.40 (s, 3H).
	With sodium hydroxide; In tert-butyl alcohol; at 20℃;	A mixture of <strong>[52-67-5]D-penicillamine</strong> (5.0 g, 1.0 eq), Boc anhydride (1.5 eq), NaOH (1.5 eq) in tert-butanol (100 mL) was stirred at 20 C overnight. The mixture was diluted with ethyl acetate, washed with aq. sodium bisulfate, dried over Mg504, and concentrated to a solid to afford compound (29a).

Reference： [1]Patent: US5187305,1993,A
[2]Patent: WO2018/174839,2018,A1 .Location in patent: Paragraph 0371

29
[ 52-67-5 ]
[ 623-00-7 ]
[ 116247-25-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In methanol; water;	Example 4 N-(4'-bromobenzoyl)-<strong>[52-67-5]D-penicillamine</strong> 36.4 g (0.2 mole) 4-bromobenzonitrile, 29.8 g (0.2 mole) <strong>[52-67-5]D-penicillamine</strong> and 13.8 g (0.1 mole) potassium carbonate were heated in 350 ml methanol and 150 ml water for 6 hours at the boiling point. After the mixture was acidified with concentrated hydrochloric acid to pH 4, it was heated one hour to a boil. After it cooled off, 53.6 g (81% of theory) of the product were isolated as a colorless precipitate with a melting point of 176 C.

Reference： [1]Patent: US4918223,1990,A

30
[ 52-67-5 ]
[ 824-94-2 ]
S-Methoxybenzyl-D-penicillamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In water;	Y. S-Methoxybenzyl-<strong>[52-67-5]D-penicillamine</strong> (27) To a suspension of D-Penicillamine (99.7 g; 668 mmol) in a mixture of oxygen-free isopropanol (590 ml) and oxygen-free water (470 ml), triethylamine (187 ml; 1330 mmol) was added under cooling. To the resultant suspension, p-methoxybenzyl chloride (136 g; 868 mmol) was dropwise added, and the mixture was stirred at room temperature overnight. The reaction mixture was combined with water (1000 ml), adjusted to pH 3 with 3N hydrochloric acid and allowed to stand under cooling. The precipitated crystals were collected by filtration and washed with water to give Compound (27) (174 g; yield, 97%).

Reference： [1]Patent: US5071636,1991,A

31
[ 52-67-5 ]
[ 65-22-5 ]
5,5-Dimethyl-2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridyl)-thiazolidine-4(S)-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
2.26 g (75.7%)	With potassium hydroxide; In water;	EXAMPLE 16 5,5-Dimethyl-2-(3-hydroxy-5-hydroxymethyl-2-methyl-4-pyridyl)-thiazolidine-4(S)-carboxylic acid 2.03 g (10 mmoles) of pyridoxal hydrochloride are added to a solution containing 1.50 g (10 mmoles) of <strong>[52-67-5]D-penicillamine</strong> and 0.56 g of potassium hydroxide in 10 ml of water. After stirring for 16 hours, the precipitate is filtered out to give the title acid in a yield of 2.26 g (75.7%) which can be purified by boiling with ethanol, m.p.: 201-202 C., [alpha]D25 =+68.1. Analysis: (Molecular weight: 298.3): Calculated: N %=9.29; S %=10.74. Found: N %=9.30, S %=10.54. IR (cm-1): 3340 and 3292 (OH), 1725 (CO). 1 H-NMR (delta, ppm): 1.66 and 1.83 (C-methyl, trans), 1.71 and 1.91 (C-methyl, cis), 2.83 (aromatic methyl), about 5 (CH2), 6.56 (H-2) (cis), 6.68 (H-4) trans.

Reference： [1]Patent: US4775675,1988,A

32
[ 52-67-5 ]
[ 30084-91-4 ]
5,5-Dimethyl-2-(5-indanyl)-thiazolidine-4(S)-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	EXAMPLE 8 5,5-Dimethyl-2-(5-indanyl)-thiazolidine-4(S)-carboxylic acid 1.44 g (10 mmoles) of 5-formylindane are portionwise added to a solution containing 1.5 g of D-penicillamine in 100 ml of methanol at room temperature while stirring. After 48 hours, the mixture is evaporated to dryness. The residue is dissolved in ether with boiling, treated with activated carbon and filtered. The crude product is precipitated by adding petroleum ether.

Reference： [1]Patent: US4775675,1988,A

33
[ 123-75-1 ]
[ 52-67-5 ]
4-carboxy-2,5,5-trimethylthiazolidine-2-acetopyrrolidide [ No CAS ]
[ 110-54-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	In benzene;	EXAMPLE 3 To a solution of 3.6 g (50 mmoles) of pyrrolidine in 50 mg of anhydrous benzene was added dropwise a solution of 4.2 g (50 mmoles) of diketene in 50 ml of anhydrous benzene at 0-5 C. over 2 hours. The mixture was allowed to stand at room temperature for 2 hours, and the solvent was distilled off to a half its volume under reduced pressure. To the residue was added 5 g (34 mmoles) of <strong>[52-67-5]D-penicillamine</strong>. The mixture was heated at 80 C. with stirring under a stream of argon for an hour to obtain a pale yellow and clear reaction mixture. The reaction mixture was filtered, the solvent was distilled off and the resulting residue was washed with a mixture of n-hexane and ether. The viscous residue thus obtained was crystallized from hot benzene and further recrystallized from benzene to give 9.5 g of 4-carboxy-2,5,5-trimethylthiazolidine-2-acetopyrrolidide as colorless prisms. Yield: 90% m.p. 101-102 C. IR (Nujol): 3500-3400, 1600 cm-1 NMR (CDCl3): delta=1.32 (3H, s), 1.68 (3H, s), 1.72 (3H, s), 2.9 (2H, s), 4.07 (1H, s)

Reference： [1]Patent: US4398026,1983,A

34
[ 52-67-5 ]
[ 2044-64-6 ]
4-carboxy-2,5,5-trimethylthiazolidine-2-N,N-dimethylacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With magnesium sulfate; In benzene;	EXAMPLE 1 A suspension of 2.00 g (13.4 mmoles) of <strong>[52-67-5]D-penicillamine</strong> and 1.73 g (13.4 mmoles) of N,N-dimethylacetoacetamide in 15 ml of dry benzene, and 0.6 g of anhydrous magnesium sulfate was refluxed for 3.5 hours under a stream of argon. The reaction mixture became clear and then the solvent was distilled off. The resulting residue was dissolved in hot methyl alcohol. Insolubles were removed by filtration and the solvent was again distilled off. The residue was crystallized from chloroform and further recrystallized from ethyl alcohol-ether to give 2.3 g of 4-carboxy-2,5,5-trimethylthiazolidine-2-N,N-dimethylacetamide as colorless prisms. Yield: 66% m.p. 140-142 C. IR(Nujol): 3560, 3450, 1595 cm-1 NMR (CDCl3): delta=1.33 (3H, s), 1.70 (3H, s), 1.75 (3H, s), 3.00 (3H, s), 3.10 (3H, s), 4.07 (1H, s)

Reference： [1]Patent: US4398026,1983,A

35
5-mercaptopyridoxine Bunte salt [ No CAS ]
[ 52-67-5 ]
[ 703-46-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; In tetrahydrofuran;	EXAMPLE 22 5-Mercaptopyridoxine Mixed Disulfide with Penicillamine, Dihydrochloride The Bunte salt (0.01 mole) from Example 21, 0.01 mole of penicillamine and 3 molecular equivalents of sodium hydroxide (2.5 N aqueous solution) were warmed together on a steam bath for 2 hours. After cooling the mixture was extracted with 2 * 50 ml. of ethyl acetate. The extract was dried over magnesium sulfate and concentrated to dryness. The residue was taken up in tetrahydrofuran and treated with hydrogen chloride which caused precipitation of 5-mercaptopyridoxine mixed disulfide with penicillamine, dihydrochloride, m.p. 171-175C. (dec.).

Reference： [1]Patent: US3971797,1976,A

36
[ 95-53-4 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
0.49 g (32.9%)	With acetic acid; In methanol; water; toluene;	EXAMPLE 14 3.26 g (0.01 mole) of benzylpenilloic acid hydrate, 3.21 g (0.03 mole) of o-toluidine and 20 ml of toluene were added to a solution of 3.60 g (0.06 mole) of acetic acid in 30 ml of water. The mixture was heated under reflux, with stirring, for 4 hours in a nitrogen atmosphere. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The aqueous layer was separated, washed with chloroform and concentrated to half volume. After standing overnight at room temperature, the crystals which had formed were removed by filtration. The filtrate was concentrated in vacuo and methanol was added to the residue. The remaining undissolved crystals were collected by filtration, washed with a small amount of cold methanol and dried in vacuo to give D-penicillamine as colorless crystals: yield 0.49 g (32.9%), m.p. 201-202 C.

Reference： [1]Patent: US4150240,1979,A

37
acid α-phenethylamide [ No CAS ]
[ 106-47-8 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
73.2%	With acetic acid; In methanol; water;	EXAMPLE 16 5.12 g (0.04 mole) of p-chloroaniline and 9.12 g (0.02 mole) of benzylpenicilloic acid alpha-phenethylamide were added to a solution of 2.4 g (0.04 mole) of acetic acid in 50 ml of water. The mixture was heated under reflux, with stirring, for 3 hours in a nitrogen atmosphere. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The crystals which formed were separated by filtration, washed with a small amount of water and discarded. The filtrate and washings were combined, washed with chloroform, and concentrated in vacuo. Methanol was added to the residue. The crystals which remained undissolved were collected by filtration, washed with a small amount of cold methanol, and dried in vacuo to give D-penicillamine as colorless crystals: yield 2.24g (75.2%), m. p. 204-205 C. By substituting phenoxymethylpenicilloic acid alpha-benzylamide for benzylpenicilloic acid alpha-phenethylamide in the above procedure, D-penicillamine was obtained in a yield of 73.2%.

Reference： [1]Patent: US4150240,1979,A

38
acid α-phenethylamide [ No CAS ]
[ 95-54-5 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
1.36 g (91.3%)	With acetic acid; In methanol; water;	EXAMPLE 2 To a solution of 0.6 g (0.01 mole) of acetic acid in 30 ml of water, 4.56 g (0.01 mole) of benzylpenicilloic acid alpha-phenethylamide and 1.08 g (0.01 mole) of o-phenylenediamine were added. The mixture was heated under nitrogen in an oil bath at 100 C. for 45 minutes. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The crystals which formed (by-product) were separated by filtration, washed with a small amount of water, and discarded. The filtrate and washing were combined and concentrated in vacuo. By addition of 5 ml of methanol to the residue, the by-product was dissolved. The crystals which remained were collected by filtration, washed with one ml of cold methanol and dried in vacuo to give D-penicillamine as colorless needles: yield 1.36 g (91.3%), m.p. 204-205 C. [alpha]D20 -62.8 (c=1, 1N--NaOH). Anal. (%): Calcd, for C5 H11 O2 NS; C, 40.24; H, 7.43; N, 9.38. Found: C, 39.91; H, 7.33; N, 9.28.

Reference： [1]Patent: US4150240,1979,A

39
[ 106-49-0 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
1.25 g (83.9%)	With acetic acid; In water; toluene;	EXAMPLE 12 3.26 g (0.01 mole) of benzylpenilloic acid hydrate, 5.35 g (0.05 mole) of p-toluidine and 20 ml of toluene were added to a solution of 4.80 g (0.08 mole) of acetic acid in 30 ml of water. The mixture was heated under reflux, with stirring, for 8 hours in a nitrogen atmosphere. The reaction mixture was then processed as described in Example 9 to give D-penicillamine as colorless crystals: yield 1.25 g (83.9%), m.p. 200-201 C.

Reference： [1]Patent: US4150240,1979,A

40
[ 137-07-5 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
1.90 g (79.8%)	With acetic acid; In methanol; water;	EXAMPLE 6 2.0 g (0.016 mole) of o-aminothiophenol and 5.22 g (0.016 mole) of benzylpenilloic acid hydrate were added to a solution of 3.6 g (0.06 mole) of acetic acid in 30 ml of water, there the mixture was heated under reflux, with stirring, for 2 hours in a nitrogen atmosphere. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The crystals which separated from solution were removed by filtration, washed with a small amount of water and discarded. The filtrate and washings were combined and concentrated in vacuo. Methanol was added to the residue. The remaining undissolved crystals were collected by filtration, washed with a small amount of cold methanol, and dried in vacuo to give D-penicillamine as colorless crystals: yield 1.90 g (79.8%), m.p. 203-204 C.
1.17 g (78.5%)		EXAMPLE 21 A mixture of 3.26 g (0.01 mole) of benzylpenilloic acid hydrate and 1.38 g (0.011 mole) of o-aminothiophenol in 20 ml of tolune was heated under reflux, with stirring, for 2 hours in a nitrogen atmosphere. The resulting mixture was allowed to stand at room temperature. The precipitated solid was separated by filtration, washed with chloroform and a small amount of cold methanol, and dried in vacuo to give D-penicillamine as colorless crystals: yield 1.17 g (78.5%), m.p. 205-206C.
1.13 g (75.7%)	With acetic acid; In methanol; water; toluene;	EXAMPLE 7 To a solution of 2.40 g (0.04 mole) of acetic acid in 20 ml of water, 3.26 g (0.01 mole) of benzylpenilloic acid hydrate, 1.38 g (0.011 mole) of o-aminothiophenol and 20 ml of toluene were added. The mixture was heated under reflux, with stirring, for 2 hours in a nitrogen atmosphere. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The aqueous layer was separated and concentrated in vacuo. A small amount of methanol was added to the residue. The undissolved crystals were collected by filtration, washed with a small amount of cold methanol and dried in vacuo to give D-penicillamine as colorless crystals: yield 1.13 g (75.7%), m.p. 203-204 C.

1.03 g (69.1%)

With acetic acid; In water;

EXAMPLE 8 To a solution of 2.4 g (0.04 mole) of acetic acid in 20 ml of water, were added 1.38 g (0.011 mole) of o-aminothiophenol and 3.52 g (0.01 mole) of benzylpenicilloic acid. The mixture was heated under reflux, with stirring, for 2.5 hours in a nitrogen atmosphere. The reaction mixture was then treated as described in Example 6 to give D-penicillamine as colorless crystals: yield 1.03 g (69.1%), m.p. 202-203 C.

Reference： [1]Patent: US4150240,1979,A
[2]Patent: US4150240,1979,A
[3]Patent: US4150240,1979,A
[4]Patent: US4150240,1979,A

41
acid α-phenethylamide [ No CAS ]
[ 137-07-5 ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
1.23 g (82.6%)	With acetic acid; In methanol; water;	EXAMPLE 4 To a solution of 1.80 g (0.03 mole) of acetic acid in 30 ml of water, 4.56 g (0.01 mole) of benzylpenicilloic acid alpha-phenethylamide and 1.25 g (0.01 mole) of o-aminothiophenol were added. The mixture was heated under reflux, with stirring, for 1.5 hours in a nitrogen atmosphere. After the completion of the reaction, the resulting mixture was allowed to stand at room temperature for an hour. The crystals which formed (by-product precipitate) were separated by filtration, washed with a small amount of water and discarded. The filtrate and washings were combined and concentrated in vacuo. A small amount of methanol was added to the residue. The remaining, undissolved crystals were collected by filtration, washed with a small amount of cold methanol and dried in vacuo to give D-penicillamine as colorless crystals; yield 1.23 g (82.6%), m.p. 204-205 C., [alpha]D20 -62.8 (c=1, 1N--NaOH). Anal. (%): Calcd, for C5 H11 O2 NS; C, 40.24; H, 7.43; N, 9.38. Found: C, 40.12; H, 7.35; N, 9.24.

Reference： [1]Patent: US4150240,1979,A

42
4-butynyloxybenzenesulfonyl chloride [ No CAS ]
[ 52-67-5 ]
[ 540-51-2 ]
N-[4-(2 butynyloxy)phenyl]-sulfonyl}-3-[(2-hydroxyethyl)sulfanyl]valine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89.6%	With sodium hydroxide; sodium carbonate; In methanol; water; N,N-dimethyl-formamide;	Step 1 A solution of <strong>[52-67-5]D-penicillamine</strong> (0.5 g, 3.35 mmol) in methanol (5 mL) was cooled to 0 C. and crushed sodium hydroxide (0.28 g, 6.87 mmol) was added to give a clear solution. 2-Bromoethanol (0.26 mL, 3.71 mmol) was added and stirred at 0 C. for 1 h and at room temperature for an additional 1.5 h. The reaction was concentrated, and the oily residue was dissolved in 3 mL water and 6 mL DMF and stirred with sodium carbonate (0.82 g 7.2 mmol) and 4butynyloxy-benzenesufonyl chloride (0.78 g, 3.18 mmol) at room temperature overnight. The reaction was concentrated and the residue was extracted with ethyl acetate and water. The aqueous layer was acidified to pH ~3 with concentrated HCl and extracted with ethyl acetate. The second ethyl acetate extract was washed with water and brine, dried over sodium sulfate, filtered and concentrated to obtain 1.2 g of N-[4-(2 butynyloxy)phenyl]sulfonyl}-3-[(2-hydroxyethyl)sulfanyl]valine as an oil. Yield 89.6%. Electrospray Mass Spec 400.1 (M-H)-.

Reference： [1]Patent: US6225311,2001,B1

43
[ 52-67-5 ]
[ 627-18-9 ]
[ 287407-33-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; In ethanol;	Step 1 A solution of 2N sodium hydroxide (11.3 mL, 22.7 mmol) was added to D-(-)-penicillamine (2.5 g, 16.8 mmol) at 0 C. Once all the solid was dissolved, a solution of 3-bromopropanol (3.03 g, 21.8 mmol) in ethanol (17 mL) was slowly added at 0 C. and the resulting mixture was stirred for 15 h at room temperature. The mixture was treated with 1N hydrochloric acid until pH is ~6 and the solvents were removed to obtain (2S)-2-amino-3-[(3-hydroxypropyl)sulfanyl]-3-methylbutanoic acid as a white solid.

Reference： [1]Patent: US6225311,2001,B1

44
[ 52-67-5 ]
(3S)-2,2-dimethyl-tetrahydro-2H-1,4-thiazine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With chloro-trimethyl-silane; 1,8-diazabicyclo[5.4.0]undec-7-ene; In methanol; 1,1-dichloroethane; N,N-dimethyl-formamide;	Step 1 To a 0 suspension of 14.92 g (0.10 mmol) of <strong>[52-67-5]D-penicillamine</strong> in 300 mL of dichloroethane and 2.0 mL of DMF was added 22.4 mL of DBU followed by 19.0 mL of trimethylsilyl chloride. The ice bath was removed and the reaction was stirred for 3h, after which an additional 29.9 mL of DBU was added. The reaction was stirred overnight at room temperature and then 10 mL of methanol was added and the reaction was stirred for 1h. The resulting white precipitate was filtered off, washed with 10 mL of methanol and dried in vacuo to provide 16 g of (3 S)-2,2-dimethyl-3-thiomorpholine carboxylic acid as a white solid.

Reference： [1]Patent: US6225311,2001,B1

45
[ 13965-31-6 ]
[ 52-67-5 ]
Pt(η2-SC(CH3)2CH(NH2)COO-N,S)(2,2'-bipyridine) [ No CAS ]

Reference： [1]Inorganic Chemistry,1995,vol. 34,p. 4441 - 4446
Inorg. Chem.,

46
[ 51146-91-9 ]
[ 52-67-5 ]
[ 1022085-60-4 ]

Yield	Reaction Conditions	Operation in experiment
75%		A portion of 4-(2-bromoacetylammo)benzenearsonic acid (500 mg, 1.479 mmol) was dissolved in aqueous NaHCO3 solution (420 mg, 4.999 mmol) in H2O (10 mL) and added drop-wise over about 1 min to a solution of (S)-penicillamine (265 mg, 1.77 mmol) in an aqueous NaHCO3 solution (640 mg, 7.618 mmol) in H2O (15 mL). The addition took place in a 100 mL round-bottom flask and the clear solution was stirred on a low speed for 4 h. The solution was acidified with 98% H2SO4 (about 0.25 mL) to pH 5. A 1:1 acetone :ethanol (500 mL) solution was stirred vigorously, and the acidified solution was added drop-wise over about 5 min to yield a white precipitate. The supernatant was centrifuged, which was decanted, and the resulting white solid was further washed and re- centrifuged with 1:1 acetone:ethanol (25 mL x 2), transferred with 1:1 acetone:ethanol (50 mL) into a 100 mL pear-shaped flask and dried on the rotary evaporator at 25 0C for 2 h. The resulting (S)-Penicillamine-arsonic acid was found to be about 44% pure by internal standard 1H-NMR spectroscopy and was used without further purification (1.022 g, 75% yield). The structure of (S)-Penicillamine-arsonic acid was confirmed by MS, 1H- NMR and 2D NMR. The main impurity was water as the final product is extremely hygroscopic. The molecular weight is 406.28 g/mole.

Reference： [1]Patent: WO2008/52279,2008,A1 .Location in patent: Page/Page column 30
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6209 - 6216

47
[ 1070872-42-2 ]
[ 52-67-5 ]
4-(N-(S-penicillaminylacetyl)amino) phenylarsonous acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26.5%		A portion of the 4-(2-bromoacetylamino)benzenearsonous acid (500 mg, 1.553 mmol) was dissolved in nitrogen-flushed DMSO (10 mL) and added drop-wise over about 1 min to an solution of S-penicillamine (265 mg, 1.77 mmol) in an aqueous NaHCO3 solution (840 mg, 10 mmol) which used nitrogen-saturated H2O (20 mL). The addition took place in a 100 mL round-bottom flask and the clear solution was stirred on a low speed under argon for 4 h. The solution was acidified with 98% H2SO4 (about 0.2 mL) to pH 5. Acetone (500 mL) was stirred vigorously, and the acidified solution was added drop-wise over EPO <DP n="30"/>about 5 min to yield a white precipitate. The supernatant was centrifuged, decanted, and the resulting white solid was further washed and re-centrifuged with acetone (20 mL x 2), transferred with acetone (40 mL) into a 100 mL pear-shaped flask and dried on the rotary evaporator at 25 C for 2 h. Crude Penicillamine-arsenoxide was found to be about 30% pure by internal standard 1H-NMR. Crude (S)-Penicillamine-arsenoxide (100.2 mg, 0.077 mmol as 30% pure) was dissolved in nitrogen-saturated H2O (2.5 mL) and purified on a Low Pressure Liquid Chromatography system. The conditions used were a 30 cm column with a 1.25 cm internal radius, nitrogen-saturated H2O as the running buffer, Biogel P-2 resin and a rate of 0.25mL/min. The second peak was collected in a 50 mL Falcon tube, frozen in liquid N2, freeze-dried for 3 days, and placed in a desiccator for 1 day to yield dried pure (S)- Penicillamine-arsenoxide (20.3 mg, 0.052 mmol). The process was repeated with more portions of crude Penicillamine-arsenoxide (696 mg in total) and this yielded purified (S)- Penicillamine-arsenoxide (114 mg, 26.5% yield). The structure of (S)-Penicillamine- arsenoxide (Fig. 1) was confirmed by MS, 1H-NMR and 2D NMR. The purity obtained was 90% by an arsenical activity assay. The main impurity was water as the final product is extremely hygroscopic. The molecular weight of (S)-Penicillamine-arsenxoide is 390.28 g/mole.1H-NMR (300 MHz, D2O): delta 1.32(s, 3H), 1.53(s, 3H), 3.55(d, J=3.4Hz, 2H), 3.63 (s, IH), 7.52(d, J=8.3Hz, 2H), 7.68(d, J=8.3Hz, 2H). The proton NMR spectrum (Fig. 2) was recorded on a Bruker, dual channel probe NMR spectrometer. Rapid keto-enol tautomerism and subsequent deuterium replacement results in the loss of the doublet peak at delta 3.5518 which occurs over Ih. This can be monitored using time-dependant NMR.13C-NMR (D2O): delta 23.15, 26.83, 33.12, 46.75, 61.36, 121.62, 130.04, 139, 144, 170.The structure of (S)-Penicillamine-arsenoxide was also confirmed by an HMBC experiment (2D 1H-13C multiple bond coupling, see Fig 3).MS: m/z 413.011678 (M+Na)+ (C13H19SO5N2AsNa requires 413.012285). (Fig 4)

Reference： [1]Bioconjugate Chemistry,2018,vol. 29,p. 546 - 558
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 6209 - 6216
[3]Patent: WO2008/52279,2008,A1 .Location in patent: Page/Page column 28-29

48
ferrous(II) sulfate heptahydrate [ No CAS ]
[ 52-67-5 ]
[ 10102-43-9 ]
di-μ-penicillamine-tetranitrosyl di-iron sulphate pentahydrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11.3%	In water; at 20℃;Inert atmosphere;	Di-mu-penicillamine-tetranitrosyl di-iron sulphate (Fe7S3N6CDH32O17) (II) was prepared by reacting iron sulphate (II) with <strong>[52-67-5]D-penicillamine</strong> in a ratio 1:3. The reaction was carried out using a standard vacuum line and Shlenk's technology under nitrogen at room temperature. Oxygen was preliminary removed from water using the method of triplicate freezing and pumping off under vacuum. To a dry mixture comprising 0.42 g (1.5 mmol) iron sulphate heptahydrate and 0.68 g (4.5 mmol) <strong>[52-67-5]D-penicillamine</strong>, 10 ml prepared water were added. Nitrogen monoxide produced according to the known technique [Yu. V. Karyakin and I. I. Angelov. Chistiye khimicheskiye veshchestva (Pure chemical substances), Moscow: Khimiya publishing house, 1974, 23] was passed through the dark-violet solution formed. During the reaction, the solution attained dark-red color. Small spicular red crystals gradually filling all the solution volume were appearing in 10 to 12 minutes on the reaction vessel walls. They were filtered under vacuum and dried under argon. Yield was: 98 mg (11.3%). The product obtained was stable in the absence of inert atmosphere for a long time. The remaining stock solution was allowed to stand for another three days at temperature 6 to 8 C. Red-orange spicular crystals thus obtained were suitable for X-ray diffraction analysis (XRD).Found, %: Fe, 15.62; S, 13.34; N, 11.89; C, 16.80, H, 4.62.Calculated, %: Fe=15.64; S=13.42; N=11.72; C=16.76, O=37.99; H=4.47.IR-spectrum (in KBr tablets), (cm-1): 1771 (strong), 1723 (strong), 1626 (medium), 1375 (medium), 1337 (medium), 1269 (medium), 1189 (medium), 1114 (medium), 1089 (medium), 746 (medium). lambdaNo: 1771

Reference： [1]Patent: US2010/190850,2010,A1 .Location in patent: Page/Page column 5

49
[ 52-67-5 ]
[ 100-44-7 ]
[ 54536-37-7 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 5977 - 5979

50
[ 52-67-5 ]
[ 939-26-4 ]
[ 1256761-30-4 ]

Reference： [1]Tetrahedron Letters,2010,vol. 51,p. 5977 - 5979

51
[ 52-67-5 ]
[ 24424-99-5 ]
[ 6482-24-2 ]
[ 856417-53-3 ]

Yield	Reaction Conditions	Operation in experiment
100%		42a) (2S)-2-((tert-butoxycarbonyl)amino)-3-((2-methoxyethyl)thio)-3-methylbutanoic acid To a solution of <strong>[52-67-5]D-penicillamine</strong> (2.98 g) and a 1 N aqueous sodium hydroxide solution (21 ml) in ethanol (20 ml) was added dropwise 2-methoxyethyl bromide (2.0 ml) while cooling to 0C. The temperature of the mixture was elevated to room temperature, and mixed at room temperature for 15 hours. To the reaction mixture were added dropwise di-tert-butyl dicarbonate (5.1 ml) and a 1 N aqueous sodium hydroxide solution (22 ml), and mixed at room temperature for 15 hours. Ethanol was distilled off under reduced pressure, and then washed with diethyl ether. The aqueous layer was acidified with a 5% aqueous citric acid solution, and then extracted with ethyl acetate. The extract was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound as a brown oil (6.3 g, quantitative). NMR (CDCl3) delta: 1.22-1.29 (6H, m), 1.45-1.46 (9H, s), 2.81-2.85 (1H, m), 3.41 (3H, m), 3.54-3.63 (2H, m), 4.34-4.38 (1H, m), 5.50-5.54 (1H, m), 6.34 (1H, s).

Reference： [1]Patent: EP1695961,2006,A1 .Location in patent: Page/Page column 56-57

52
[ 76-84-6 ]
[ 52-67-5 ]
[ 150025-01-7 ]

Yield	Reaction Conditions	Operation in experiment
53.6%	With boron trifluoride diethyl etherate; acetic acid; at 20℃; for 2h;	Synthetic Example 18; (S)-2-(Benzothiazol-2-yl)amino-3-mercapto-3-methyl-butyric acid; Step 1. (SV2-Amino-3-methyl-3-triphenylmethylsulfanyl)-butyric acid; To a stirred solution of (S)-penicillamine (1.492 g, 10 mmol) and triphenylmethanol (3.12 g, 12 mmol) in AcOH (10 mL), was added BF3-Et2O (2.2 mL) dropwise at room temperature. The reaction was stirred for 2 hours. The mixture was then poured into aqueous sodium acetate (15 mL) and the white solid that separated was collected by filtration. The solid was washed with Et2O (3 x 10 mL), and dried in vacuum to afford S-trityl-protected penicillamine as a white powder (2.1g, 53.6%). 1H-NMR (DMSO-d6, ppm, 500 MHz): delta = 7.22-7.57 (m, 15H), 1.94 (s, IH), 1.16 (s, 3H), 1.11 (s, 3H). MS (ESI): 414(M+23) +.

Reference： [1]Patent: WO2009/151744,2009,A1 .Location in patent: Page/Page column 108

53
[ 52-67-5 ]
[ 115-11-7 ]
[ 1333478-51-5 ]

Yield	Reaction Conditions	Operation in experiment
		Example Synthesis 1; FIG. 1 shows a five step synthesis process for the composition of formula 1.; Step 1: (2S)-2-amino-3-methyl-3-sulfanyl-butanoic acid (initial compound 1) and Dichloromethane (DCM) were mixed together as a reaction mixture in a pressure bottle containing a magnetic stirrer. The pressure bottle containing the reaction mixture (intermediate compound 1) was securely closed with a rubber septum. The pressure bottle containing the reaction mixture was further cooled in 2-isoproponol/dry ice at 7-8 C. in the dry ice bath. Condensed isobutylene was transferred to the pressure bottle, using a cannula, followed by adding a few drops of sulfuric acid to the reaction mixture. The addition of isobutylene was continued for a period of 2 hours. Stirring of the reaction mixture was continued at room temperature for an additional 16 hours. The pressure bottle was kept in i-PrOH/dry ice bath and rubber septum was carefully removed. The reaction mixture was allowed to degas fully by stirring for several minutes. Saturated aqueous NaHCO3 was added to the reaction mixture, and the resultant reaction mixture was stirred for 2 hours at room temperature. The pH of the aqueous layer was measured and recorded as pH 8. Water was added for the removal of the emulsion that was formed during the neutralization step. The aqueous layer was treated using with DCM and then extracted. The entire DCM extracts were pooled together. The pooled DCM extracts were washed with saturated aqueous NaHCO3, water, and saturated aqueous NaCl solution. The resultant organic layer was dried in under MgSO4 atmosphere, concentrated and filtered under reduced pressure to yield intermediate compound 2.

Reference： [1]Patent: US2011/218235,2011,A1 .Location in patent: Page/Page column 6

54
[ 93794-39-9 ]
[ 52-67-5 ]
[ 76-05-1 ]
[ 1334386-03-6 ]

Yield	Reaction Conditions	Operation in experiment
74%		Compound 25 (870 mg, 4.7 mmol) and <strong>[52-67-5]D-penicillamine</strong> (710 mg, 4.7 mmol) were dissolved in DMSO (20 mL), and NaOH (430 mg, 10.7 mmol) was added. The reaction was stirred at r.t. for 3 h. The mixture was then acidified with 6N HCl (1.5 mL) to pH 3-4, then purified by flash chromatography eluting with acetonitrile/distilled water (with 0.05% TFA) giving compound 26 as a salt (1.0 g, 74%, purity: 97%). 1H NMR (DMSO-d6, 500 MHz): delta 6.97 (d, J=8.0 Hz, 1H), 6.37 (s, 1H), 6.34 (d, J=8.5 Hz, 1H), 4.38 (s, 1H), 3.66 (s, 3H), 1.63 (s, 3H), 1.40 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): delta 170.5, 157.8, 151.0, 124.1, 122.3, 104.5, 103.0, 76.2, 58.7, 55.1, 27.7, 25.5; ESI-MS (m/z): 297.1 [M+1]+.

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 24

55
[ 615-18-9 ]
[ 52-67-5 ]
[ 1334385-86-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; methanol;	Compound 1: To a solution of D-(-)-penicillamine (6.2 g, 41.5 mmol) and DIPEA (14 mL, 78.5 mmol) in 150 mL of MeOH/THF (1:2 v/v), was added 2-chlorobenzoxazole (7.4 g, 48.0 mmol) in a dropwise manner. The reaction was stirred overnight. The mixture was then concentrated in vacuo to afford a pale yellow oil, which was treated with 150 mL of concentrated HCl to produce a white solid. This product was filtered, washed with acetone (250 mL) and Et2O (350 mL) to yield (S)-2-(2-hydroxyphenylimino)-thiazolidine-5,5-dimethyl-4-carboxylic acid hydrochloride as a white solid (7.0 g, yield 56%).

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 22

56
[ 52-67-5 ]
[ 54120-91-1 ]
[ 1334386-09-2 ]

Yield	Reaction Conditions	Operation in experiment
45%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Compound 29 (1.84 g, 9.3 mmol) and <strong>[52-67-5]D-penicillamine</strong> (1.4 g, 9.3 mmol) were dissolved in DMF (5 mL). Subsequently DIPEA (2 mL) was added. The reaction mixture was stirred at r.t. overnight. The reaction was diluted with ethyl acetate (200 mL) and the solid was filtered off. The resultant organic phase was washed with water and the resulting aqueous phases were combined and concentrated. The resulting residue was purified by preparative HPLC eluting with an H2O/CH3CN gradient containing 0.05% TFA. Compound 31 was obtained as white solid (1.28 g, yield 45%, purity: 100%). 1H NMR (DMSO-d6, 500 MHz): delta 8.24 (brs, 1H), 8.05 (d, J=9.0 Hz, 1H), 7.09 (d, J=9.0 Hz, 1H), 4.59 (s, 1H), 1.70 (s, 3H), 1.49 (s, 3H); 13C NMR (MeOD, 125 MHz): delta 169.3, 158.3, 139.8, 124.5, 121.7, 118.4, 116.9, 115.5, 72.7, 57.8, 28.9, 25.3; ESI-MS (m/z): 312.0 [M+1]+.

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 24-25

57
[ 3621-82-7 ]
[ 52-67-5 ]
[ 1334386-05-8 ]

Yield	Reaction Conditions	Operation in experiment
58%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 3h;	Compound 15 (693 mg, 3.7 mmol) and D-penicillamine (550 mg, 3.7 mmol) were dissolved in 4 mL of DMF. Subsequently DIPEA (960 mg, 7.5 mmol) was added. The reaction was stirred at r.t. for 3 h. The resultant mixture was concentrated and the crude product was purified by preparative HPLC eluting with an H2O/CH3CN gradient containing 0.05percent TFA, giving compound 28 as a pink solid (652 mg, yield 58percent). 1H NMR (DMSO-d6, 500 MHz): delta 7.17 (brs, 1H), 6.81-6.75 (m, 2H), 4.37 (s, 1H), 1.62 (s, 3H), 1.39 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): delta 170.7, 159.4, 149.4, 127.2, 122.4, 118.7, 116.5, 28.3, 25.5; ESI-MS (m/z): 301.1 [M+1]+

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 24

58
[ 3770-60-3 ]
[ 52-67-5 ]
[ 1334386-00-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	Compound 22 (1.0 g, 6.0 mmol) and (S)-penicillamine (983 mg, 6.6 mmol) were dissolved in 5 mL of DMF. Subsequently, DIPEA (1.55 mL, 12 mmol) was added. The reaction was stirred at r.t. overnight. The mixture was concentrated and the resultant residue was purified by prep-HPLC eluting with an H2O/CH3CN gradient containing 0.05% TFA. The resultant product was recrystallized from MeOH and diethyl ether to give compound 24 as a salt. 1H NMR (DMSO-d6, 500 MHz): delta 6.99 (d, J=6.0 Hz, 1H), 6.61 (s, 1H), 6.54 (d, J=7.5 Hz, 1H), 4.39 (s, 1H), 2.18 (s, 3H), 1.63 (s, 3H), 1.40 (s, 3H); 13C NMR (DMSO-d6, 125 MHz): delta 170.8, 160.5, 148.5, 134.2, 127.5, 121.9, 119.6, 118.1, 77.0, 58.7, 28.1, 25.5, 20.4; ESI-MS (m/z): 281.1 [M+1]+.

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 24

59
[ 3621-81-6 ]
[ 52-67-5 ]
[ 1354389-51-7 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	Compound 21: Compound 19 (1.65 g, 8.8 mmol) and <strong>[52-67-5]D-penicillamine</strong> (1.40 g, 9.4 mmol) were dissolved in 10 mL of DMF. Subsequently, DIPEA (2.5 mL) was added. The resulting mixture was stirred at r.t. for 2 hours. The reaction was then diluted with water (200 mL) and washed with ethyl acetate (2*150 mL). The aqueous phase was concentrated and the residue was purified by prep-HPLC eluting with an H2O/CH3CN gradient containing 0.05% TFA to give (S)-2-(2-hydroxy-5-chlorophenylamino)-thiazoline-5,5-dimethyl-4-carboxylic acid as a white solid TFA salt (1.2 g, yield 45%, purity: 100%). 1H NMR (DMSO-d6, 400 MHz): delta 7.37 (s, 1H), 7.21 (d, J=8.0 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 4.61 (brs, 1H), 1.70 (s, 3H), 1.49 (s, 3H); 13C NMR (DMSO-d6, 100 MHz): delta 168.6, 150.5, 128.3, 125.3, 122.1, 115.5, 113.3, 72.2, 57.4, 28.5, 24.7; ESI-MS (m/z): 301.0 [M+1]+

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 24

60
[ 890709-11-2 ]
[ 52-67-5 ]
[ 1334386-12-7 ]

Yield	Reaction Conditions	Operation in experiment
30%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0℃; for 0.25h;	Compound 13 (2.0 g, 8.1 mmol) and <strong>[52-67-5]D-penicillamine</strong> (1.22 g, 8.1 mmol) were dissolved in DMF (20 mL) and DIPEA (3.3 g, 32.6 mmol) was added. The reaction was stirred at 0 C. for 15 min. The mixture was then concentrated and the resultant crude product was purified by preparative HPLC eluting with an H2O/CH3CN gradient containing 0.05% TFA, giving compound 33 as a white solid (380 mg, 30%). 1H NMR (D2O, 500 MHz): delta 7.82 (s, 1H), 7.76 (d, J=9.0 Hz, 1H), 7.19 (d, J=9.0 Hz, 1H), 3.26 (q, J=7.5 Hz, 2H), 1.70 (s, 3H), 1.51 (s, 3H), 1.49 (t, J=7.5 Hz, 3H); 13C NMR (MeOD, 125 MHz): delta 158.4, 134.4, 128.3, 118.3, 73.6, 59.5, 51.4, 29.0, 26.3, 7.7; ESI-MS (m/z): 359.0 [M+1]+.

Reference： [1]Patent: US2011/224269,2011,A1 .Location in patent: Page/Page column 25

61
[ 18024-34-5 ]
[ 52-67-5 ]
[ 7732-18-5 ]
C₃₆H₄₄Au₂N₂O₄P₂S₂*8H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium hydroxide; In ethanol; at 20℃; for 2h;	To a white suspension containing 1.0 g (1.2mmol) of [(AuCl)2(dppe)] in120 mL of EtOH was added 0.36 g (2.4mmol) of D-H2pen and 24 mL of a 0.1M aqueous KOH solution. The mixture was stirred at room temperature for 2 h, and the resulting colorless solution was evaporated to dryness. The obtained white powder was recrystallized from EtOH/water (1:1), and the esulting colorless crystals were collected by filtration.

Reference： [1]Bulletin of the Chemical Society of Japan,2013,vol. 86,p. 908 - 920

62
[ 12184-22-4 ]
[ 52-67-5 ]
Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium hydroxide; In water; at 20℃;pH 6.8;Inert atmosphere;	General procedure: 6-O-Palmitoyl l-ascorbic acid (82.3 mg (0.20 mmol) was charged in a three neck round bottom flask of 100 mL, in 10 mL of deionized, degassed water and sonicated for 2 h to induce dissolution. In a separate a three neck round bottom flask of 100 mL, 58.9 mg (0.20 mmol) of Cp2MoCl2 in 6 mL of deionized, degassed water was also sonicated for 2 h. To this solution, the 6-O-palmitoyl-l-ascorbic acid was added and the pH adjusted to 10 with 0.1 M NaOH. The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere, forming a dark-yellow precipitate. The precipitate was filtered and washed with small amounts of water. The product was purified by column chromatography, using LH20 (lipophilic sephadex 20-100 mum) as solid phase and methanol as solvent. The product was dried under vacuum for 24 h.

Reference： [1]Journal of Inorganic Biochemistry,2014,vol. 132,p. 77 - 91

63
[ 52-67-5 ]
[ 74-88-4 ]
[ 29913-84-6 ]

Yield	Reaction Conditions	Operation in experiment
99%	With sodium hydride; In methanol; at 20℃;Inert atmosphere;	S-Methyl d-penicillamine (3) was synthesized from 0.10 g (0.67 mmol) d-penicillamine (1) using 54 mul (1.3 equiv.) methyl iodide and 0.02 g (1.3 equiv.) sodium hydride in 5 ml methanol under N2 atmosphere [20] . After stirring overnight at room temperature the reaction mixture was evaporated in vacuo. The residual oil was purified by column chromatography on silica gel (ethyl acetate-hexane, 1:5, v/v) to afford compound 3 as a white solid (0.11 g, 99%). Mp: 253-260 C. 1H NMR (600 MHz, H2O:D2O, 95:5, v/v) delta (ppm) 1.31 (3H, s, betaCH3), 1.52 (3H, s, betaCH3), 2.07 (3H, s, SCH3), 3.67 (1H, s, alphaH); HRMS m/z [M+H]+ Calc 164.0745 Found 164.0687.
99%	With sodium hydride; In methanol; at 20℃;Inert atmosphere;	S-Methyl d-penicillamine (3) was synthesized from 0.10 g(0.67 mmol) d-penicillamine (1) using 54 l (1.3 equiv.) methyliodide and 0.02 g (1.3 equiv.) sodium hydride in 5 ml methanolunder N2atmosphere [20]. After stirring overnight at room temper-ature the reaction mixture was evaporated in vacuo. The residualoil was purified by column chromatography on silica gel (ethylacetate-hexane, 1:5, v/v) to afford compound 3 as a white solid (0.11 g, 99%)

Reference： [1]Chemical Physics Letters,2014,vol. 610-611,p. 62 - 69
[2]Chemical Physics Letters,2015,vol. 610-611,p. 62 - 69

64
[ 52-67-5 ]
[ 148-53-8 ]
C₁₃H₁₇NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	In methanol; water; for 2h;Reflux;	<strong>[52-67-5]D-penicillamine</strong> (0.1491 g, 1.0 mM) and 3-methoxy salicylaldehyde (0.1522 g, 1.0 mM) in 50% methanol/water (30 mL) were refluxed for two hours. The resulting solution was reduced to one third of its original volume, and cooled to room temperature. The solution was kept at room temperature closed condition for a day. Colorless crystals were collected by filtration, washed with chloroform, and dried under vacuum. The product was recrystallized with 50% methanol water mixture. Anal. Calcd for C13H17NO4S (%): C,55.11; H, 6.05; N, 4.94; S, 11.32. Found (%): C, 55.32; H, 6.24; N, 5.01; S, 11.45. IRdata (KBr, cm1): (s = strong, m= medium, b = broad). 3400-2700 (b) [nu(OH)]; 1635 (s)[nuasym(COO-)], 1369 (s) [nusym(COO)]; 1354 (m) [delta(OH)]; 1247 (s) [nu(C-O)]; 833 (w) [nu(C-S-C)]; 1H NMR (400 MHz, DMSO-d6, ppm): 1.62 (singlet (s), CH3, 3H), 1.31 (singlet(s), CH3, 3H), 3.38 (singlet, -CH-COOH, 1H), 6.69-6.92 (multiplet, aromatic H, 3H), 3.84 (singlet, 3H, OCH3), 5.79 (singlet, thiazolidine -CH-NH, 1H). Color: white. M.p. 143 C; Yield: 73%.

Reference： [1]Journal of Coordination Chemistry,2013,vol. 66,p. 1805 - 1820

65
[ 52-67-5 ]
[ 943-03-3 ]
(S)-2-(6-methoxybenzo[d]thiazol-2-yl)-5,5-dimethyl-4,5-dihydrothiazole-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium carbonate; In water; at 20℃; for 3h;	General procedure: The hydroxy- or methoxycarbonitrile derivative (1 eq) was added to the cysteine derivative (1.05 eq) and sodium carbonate (3 eq) in 5 ml water. The mixture was stirred at room temperature for three hours before addition of dilute HCl (1 M) to pH ? 3.5 - 4.0. The product was isolated by extraction with diethyl ether, washed by water, followed by evaporation

Reference： [1]European Journal of Medicinal Chemistry,2015,vol. 94,p. 140 - 148

66
[ 52-67-5 ]
[ 23315-18-6 ]

Yield	Reaction Conditions	Operation in experiment
	With cysteine dioxygenase; sodium chloride; In aq. phosphate buffer; water-d2; at 20 - 95℃; for 0.0333333h;pH 7.5;Enzymatic reaction;Kinetics;	General procedure: NMR kinetic studies were performed on a 300 JEOL nuclearmagnetic resonance spectrometer (Pleasanton, CA). All measurementswere made in Wilmad NMR tubes (standard wall, 5 mmO.D., precision, 507-PP-7). For each reaction, fully modified CDO(typically 2-25 lM) was added to a buffered substrate solutionin D2O (sodium phosphate buffer, 50 mM NaCl, pD 7.5) to initiatethe reaction at ambient temperature (20 ± 2 C). Reaction pointswere terminated by heat shock at 95 C for 2 min followed by spin-filtration to remove denatured protein. Final concentration of 1 mM trimethylsilyl propanoic acid (TMSP) was added as theinternal standard. NMR spectra were integrated using JOEL USADelta NMR data processing software (version 5.0.4). The correctedvalue of pD was obtained by adding 0.4 pD units to the valuereported by the pH electrode (Mettler Toledo InLab Expert Pro)[29].

Reference： [1]Archives of Biochemistry and Biophysics,2015,vol. 565,p. 49 - 56

67
[ 72428-60-5 ]
[ 64-17-5 ]
[ 52-67-5 ]
[ 7732-18-5 ]
C₃₇H₄₆Au₂N₂O₄P₂S₂*C₂H₆O*3H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With sodium hydroxide; at 20℃; for 2h;	To a white suspension containing 2.06 g (2.35 mmol) of [(AuCl)2(LC3)] in EtOH (70 mL) was added a colorless solution containing 0.70 g (4.70 mmol) of D-H2pen in a 0.1 M aqueous NaOH (47 mL, 4.70 mmol). The mixture was stirred at room temperature for 2 h, and the resulting colorless solution was evaporated to dryness. The white residue was washed with H2O and dried in air. Yield: 2.89 g (97%). Found: C, 38.71; H, 4.72; N, 2.39%. Calcd for [Au2(LC3)(D-Hpen)2]EtOH3H2O = Au2C39H58N2O8P2S2: C, 38.94; H, 4.86; N, 2.33%. 1HNMR spectrum (ppm from TMS, methanol-d4): 7.83-7.76 (m, 8H), 7.59-7.49 (m, 12H), 3.53 (s, 2H), 3.13-2.90 (m, br, 4H), 1.96-1.84 (m, br, 2H), 1.75 (s, 6H), 1.38 (s, 6H).

Reference： [1]Bulletin of the Chemical Society of Japan,2015,vol. 88,p. 59 - 68

68
[ 63640-04-0 ]
[ 52-67-5 ]
[ 7732-18-5 ]
C₃₈H₄₈Au₂N₂O₄P₂S₂*3H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydroxide; In ethanol; at 20℃; for 2h;	To a white suspension containing 2.07 g (2.32 mmol) of [(AuCl)2(LC4)] in EtOH (70 mL) was added a colorless solution containing 0.69 g (4.64 mmol) of D-H2pen in a 0.1 M aqueous NaOH (46 mL, 4.64 mmol). The mixture was stirred at room temperature for 2 h, and the resulting colorless solution was evaporated to dryness. The white residue was washed with H2O and dried in air. Yield: 2.38 g (88%). Found: C, 38.75; H, 4.47; N, 2.44%. Calcd for [Au2(LC4)(D-Hpen)2]*3H2O = Au2C38H54N2O7P2S2: C, 38.98; H, 4.65; N, 2.39%. IR spectrum (cm-1, KBr disk): 1625(nuCOO-), 1436, 744 (nuP-CH2-), 1104, 694 (nuP-Ph). 1H NMR spectrum (ppm from TMS, methanol-d4): 7.78-7.68 (m, 8H), 7.55-7.45 (m, 12H), 3.53 (s, 2H), 2.74-2.57 (m, br, 4H), 1.91-1.73 (s + m, br, 10H), 1.40 (s, 6H). 31P NMR spectrum (ppm from 85% H3PO4, methanol-d4): 38.1 (s).

Reference： [1]Bulletin of the Chemical Society of Japan,2015,vol. 88,p. 59 - 68

69
[ 99350-05-7 ]
[ 52-67-5 ]
[ 7732-18-5 ]
C₃₉H₅₀Au₂N₂O₄P₂S₂*3H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydroxide; In ethanol; at 20℃; for 2h;	To a white suspension containing 2.04 g (2.25 mmol) of [(AuCl)2(LC5)] in EtOH (70 mL) was added a colorless solution containing 0.67 g (4.51 mmol) of D-H2pen in a 0.1 M aqueous NaOH (45 mL, 4.51 mmol). The mixture was stirred at room temperature for 2 h, and the resulting colorless solution was evaporated to dryness. The white residue was washed with H2O and dried in air. Yield: 2.28 g (86%). Found: C, 39.79; H, 4.67; N, 2.46 %. Calcd for [Au2(LC5)(D-Hpen)2]*3H2O = Au2C39H56N2O7P2S2: C, 39.53;H, 4.76; N, 2.36%. IR spectrum (cm-1, KBr disk): 1627(nuCOO-), 1436, 743 (nuP-CH2-),1103, 694 (nuP-Ph). 1H NMR spectrum (ppm from TMS, methanol-d4): 7.77-7.72 (m, 8H), 7.52-7.51 (m, 12H), 3.54 (s, 2H), 2.60-2.55 (m, br, 4H), 1.84-1.72 (s + m, br, 8H), 1.72-1.60 (m, br, 4H), 1.38 (s, 6H). 31P NMRspectrum (ppm from 85% H3PO4, methanol-d4): 37.8 (s).

Reference： [1]Bulletin of the Chemical Society of Japan,2015,vol. 88,p. 59 - 68

70
[ 14243-64-2 ]
[ 52-67-5 ]
[Au(PPh₃)(D-Hpen)]*1.5H₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In ethanol; at 20℃; for 1.5h;	To a whitesuspension containing 1.00 g (2.02mmol) of [Au(PPh3)Cl]10 in30mL of ethanol was added 0.30 g (2.0mmol) of D-H2pen. Themixture was stirred at room temperature for 1.5 h, which gave acolorless solution. After the addition of 20mL (2.0mmol) ofan aqueous NaOH solution (0.10 M), the colorless solution wasevaporated to dryness. The residue was washed with water togive a white powder that was collected by filtration. Yield:1.14 g (89%). Anal. Found: C, 43.75; H, 4.29; N, 2.22%.Calcd for [Au(PPh3)(D-Hpen)]¢1.5H2O = C23H28NO3.5PSAu:C, 43.54; H, 4.45; N, 2.21%. IR spectrum (cm1): 1626 (COO).1HNMR spectrum (ppm from TMS, methanol-d4): delta 1.38 (s,3H), 1.84 (s, 3H), 3.56 (s, 1H), 7.527.60(m, 15H). 31PNMRspectrum (ppm from H3PO4, methanol-d4): delta 38.5 (s).

Reference： [1]Bulletin of the Chemical Society of Japan,2015,vol. 88,p. 1144 - 1146

71
nickel(II) chloride hexahydrate [ No CAS ]
[ 52-67-5 ]
[ 127099-85-8 ]
C₁₄H₂₆N₁₀Ni₂O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A suspension containing 0.15 g (1.0 mmol) of L-penicillamine, 0.10 g (1.0 mmol) of Et3N, and 0.08g (1.0 mmol) of dicyandiamide in MeOH (3 mL) was stirred at 50C for 5 min to give a clear yellow solution, to which was added a solution containing 0.12 g (0.5 mmol) of NiCl2*6H2O in MeOH (2 mL). The mixture was stirred at 50C for 8 h to give brown suspension. After filtration, the resulting brown filtrate was stood at room temperature. A small amount of dark red diamond-shaped crystals suitable for X-ray analysis were produced after 6 months.

Reference： [1]Chemistry Letters,2016,vol. 45,p. 140 - 142

72
[ 52-67-5 ]
(4Z,7Z,10Z,13Z,16Z,19Z)-N-(2-(pyridin-2-yldisulfaneyl)ethyl)-docosa-4,7,10,13,16,19-hexaenamide [ No CAS ]
[ 1538-75-6 ]
(R)-2-((tert-butoxycarbonyl)amino)-3-((2-((4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenamido)ethyl)disulfanyl)-3-methylbutanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.2%		[00231] A solution containing cysteamine hydrochloride (7.87 g, 69.3 mmol) in methanol (100 mL) was added dropwise to a solution of 2,2'-dithiopyridine (25.0 g, 1 13.6 mmol) in methanol (300 mL). The resulting reaction mixture was stirred at room temperature for 18 hours. Di-tert-butyl dicarbonate (15.1 g, 69.3 mmol) and aqueous sodium hydroxide (5M, 30 mL) were added slowly. The reaction mixture was stirred at room temperature for an additional 4 hours. The mixture was then extracted with ethyl acetate (300 mLx2). The combined organic layers were washed with brine (300 mL), dried over Na2S04 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (hexanes/ethyl acetate = 10: 1 to 5: 1) to afford tert-butyl 2-(pyridin-2-yldisulfanyl)ethylcarbamate (8.3 g, 42.3% yield) as a yellow oil. [00232] tert-Butyl 2-(pyridin-2-yldisulfanyl)ethylcarbamate (5.8 g, 25.6 mmol) was dissolved in 1,4-dioxane (30 mL) and the solution was cooled to 0C. A solution of HQ in 1,4- dioxane (5M, 20 mL) was then added dropwise. The resulting reaction mixture was stirred for 2 hours and then concentrated under reduced pressure to afford 2-(pyridin-2- yldisulfanyl)ethanamine (5.6 g, 100% yield, HC1 salt). [00233] A mixture of 2-(pyridin-2-yldisulfanyl)ethanamine (12.0 g, 64.5 mmol), DHA (51.6 mmol) and HATU (29.3 g, 77 mmol) in DCM (150 mL) was cooled to 0C and Hunig's base (25 g, 190 mmol) was added. The resulting reaction mixture was allowed to warm to room temperature and stirred for 18 hours. Saturated aqueous NH4C1 (200 mL) was added to quench the reaction and the resulting mixture was extracted with CH2CI2 (300 mLx2). The combined organic layers were washed with brine, dried over Na2S04and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (methanol/CH2Cl2 = 0.5% to 2.0%) to afford (4Z,7Z, 10Z, 13Z, 16Z, 19Z)-N-(2-(pyridin-2-yldisulfanyl)ethyl)docosa- 4,7, 10, 13, 16,19-hexaenamide as a yellow oil. [00234] A mixture of (4Z,7Z,10Z, 13Z,16Z, 19Z)-N-(2-(pyridin-2-yldisulfanyl)ethyl)docosa- 4,7, 10, 13, 16,19-hexaenamide (4.8 g, 9.6 mmol) and (S)-2-amino-3-mercapto-3-methyl butanoic acid (1.44 g, 9.6 mol) in MeOH (100 mL) were stirred at room temperature for 18 hours. Di-tert-butyl dicarbonate (2.1 g, 9.6 mmol) was then added, followed by the slow addition of 3 M aqueous sodium hydroxide solution (30 mL). The resulting reaction mixture was stirred at room temperature for 4 hours and then extracted with EtOAc (100 mLx2). The combined organic layers were washed with brine, dried over Na2S04 and concentrated under reduced pressure. The resulting residue was purified by silica gel chromatography (methanol/CH2Ci2 = 0% to 1.5%) to afford (R)-2-((tert-butoxycarbonyl)amino)-3-((2- ((4Z,7Z, 10Z, 13Z, 16Z, 19Z)-docosa-4,7, 10, 13, 16,19-hexaenamido)ethyl)disulfanyl)-3 - methylbutanoic acid (5.4 g, 88.2% yield) as a yellow oil.

Reference： [1]Patent: WO2016/86103,2016,A1 .Location in patent: Paragraph 00234

73
[ 52-67-5 ]
[ 121-44-8 ]
[ 17028-61-4 ]
copper dichloride [ No CAS ]
C₃₉H₃₉Cu₄N₆O₁₈S₃^(2-)*2C₆H₁₆N⁽¹⁺⁾ [ No CAS ]

Reference： [1]European Journal of Inorganic Chemistry,2016,vol. 2016,p. 2692 - 2695

74
[ 52-67-5 ]
[ 312-10-7 ]

Yield	Reaction Conditions	Operation in experiment
87%	With iron(III) chloride; ammonium hydroxide; oxygen; In water; for 2h;pH 9;	Method B: A solution of <strong>[52-67-5]D-penicillamine</strong> in water wasbrought to pH 9 with ammonia solution and few crystals of FeCl3 were added. Oxygen was passed through the solution until decolourisation. The solvent was evaporated and the remaining white solid was recrystallised from ethanol and water, to give the corresponding disulphide (3,3'-disulfanediylbis(2-amino-3-methylbutanoic acid, 87 %, mp 173 - 176 C) [37], which was converted to the dimethyl ester by reflux with SOCl2 in methanol [38].

Reference： [1]Letters in drug design and discovery,2016,vol. 14

75
[ 52-67-5 ]
(2,5-dioxopyrrolidin-1- yl)oxycarbonyloxymethyl acetate [ No CAS ]
(2S)-2-(acetoxymethoxycarbonylamino)-3-(acetoxymethoxycarbonylsulfanyl)-3-methyl-butanoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With trimethylamine; at 20℃;	A mixture of <strong>[52-67-5]D-penicillamine</strong> (0.10 g, 1.0 eq), (2,5-dioxopyrrolidin-1-yl)oxycarbonyloxymethyl acetate (3.0 eq), and trimethylamine (5.0 eq) in DMF (or ACN/water) (10 mL) was stirred at 20 C. overnight. The reaction was concentrated in vacuo to a residue and then purified by reverse-phase (C-18) liquid chromatography using water and acetonitrile as eluents to yield compound (11). MS (ESI): m/z 382.1 (M+H)+.
	With triethylamine; at 20℃;	A mixture of <strong>[52-67-5]D-penicillamine</strong> (0.10 g, 1.0 eq), (2,5-dioxopyrrolidin-1- yl)oxycarbonyloxymethyl acetate (3.0 eq), and trimethylamine (5.0 eq) in DMF (or ACN/water) (10 mL) was stirred at 20 C overnight. The reaction was concentrated in vacuo to a residue and then purified by reverse-phase (C-18) liquid chromatography using water and acetonitrile as eluents to yield compound (11). MS (ESI): m/z 382.1 (M+H)+.

Reference： [1]Patent: US2017/81280,2017,A1 .Location in patent: Paragraph 0232; 0337; 0338
[2]Patent: WO2018/174839,2018,A1 .Location in patent: Paragraph 0350

76
[ 52-67-5 ]
[ 640-68-6 ]

Reference： [1]Journal of Peptide Science,2017,vol. 23,p. 556 - 562

77
[ 52-67-5 ]
[ 6046-93-1 ]
C₁₀H₂₀CuN₂O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In neat (no solvent); at 20℃;	General procedure: An accurately weighted quantity of ligand dl-penicillamine1.491 g (0.01 mole) and copper(II) acetate monohydrate0.998 g (0.005 mole) were taken in an agate mortar and ground gently with pestle under neat condition at ambient temperature for 2-3 h. The reaction produced a solid powder after 30 min of grinding, which is a partly intermediate complex and partly unreacted starting material. On grinding dl-penicillamine with copper acetate monohydrate under neat condition, acetic acid was released as a by-product, which was identified by its characteristic odor (Figure 2). The formation of reaction productwas indicated by a change in color from blue to grayish blue and ascertained by cessation of acidic acid odor. Microcrystalline powder of grayish blue product was obtained and characterized as such and after washing with acetone.

Reference： [1]Inorganic and Nano-Metal Chemistry,2017,vol. 47,p. 818 - 823

78
[ 52-67-5 ]
[ 6046-93-1 ]
C₂₀H₄₂CuN₄O₈S₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In neat (no solvent); at 20℃;	An accurately weighted quantity of ligand dl-penicillamine1.491 g (0.01 mole) and copper(II) acetate monohydrate0.998 g (0.005 mole) were taken in an agate mortar and ground gently with pestle under neat condition at ambient temperature for 2-3 h. The reaction produced a solid powder after 30 min of grinding, which is a partly intermediate complex and partly unreacted starting material. On grinding dl-penicillamine with copper acetate monohydrate under neat condition, acetic acid was released as a by-product, which was identified by its characteristic odor (Figure 2). The formation of reaction productwas indicated by a change in color from blue to grayish blue and ascertained by cessation of acidic acid odor. Microcrystalline powder of grayish blue product was obtained and characterized as such and after washing with acetone.

Reference： [1]Inorganic and Nano-Metal Chemistry,2017,vol. 47,p. 818 - 823

79
[ 52-67-5 ]
C₁₂H₁₄O₅ [ No CAS ]
C₁₈H₂₅NO₆S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46.9%	In methanol; at 20℃; for 4h;	Weigh 55mg M12A loaded 25mL round bottom flask, dissolved in 5mL methanol, add 34mg of penicillamine, the reaction was stirred at room temperature for 4h. The residue was purified by preparative TLC on silica gel (chloroform: methanol = 4: 1) to give the product T44.

Reference： [1]Patent: CN107400128,2017,A .Location in patent: Paragraph 0212-0214

80
[ 52-67-5 ]
[ 38275-57-9 ]
C₁₀H₁₂N₄O₂S [ No CAS ]

Reference： [1]Chemical Science,2018,vol. 9,p. 336 - 344

81
[ 889676-37-3 ]
[ 52-67-5 ]
C₁₁H₁₅N₃O₃S [ No CAS ]

Reference： [1]Chemical Science,2018,vol. 9,p. 336 - 344

82
C₂₀H₂₆N₂O₄ [ No CAS ]
[ 52-67-5 ]

Yield	Reaction Conditions	Operation in experiment
6.9 g	With tetraphosphorus decasulfide; In acetonitrile; for 12h;Heating;	15 grams of the oxazolone was heated with 100 ml acetone in the presence of sodium acetate for 24 hours at 60C. Acetone was distilled off. The residue (intermediate compound of formula 5) was taken in acetonitrile and heated in the presence of phosphorous pentasulphide (P4S10) for 12 hours. The acetonitrile layer was distilled off. The residue was taken in methylene dichloride (MDC) and washed successively with water and brine. The MDC layer was concentrated and heated with 25 ml, 5 N HC1 for 12 hours. The HC1 layer was neutralized to obtain a solid. The solid was filtered and a slurry wash was performed employing acetic acid and methanol (1 : 1). The product was dried at 50C for 6 hours.Yield = 6.9 grams (81.4 %) Purity: 99.5%

Reference： [1]Patent: WO2018/134836,2018,A1 .Location in patent: Page/Page column 13

83
[ 52-67-5 ]
[(μ-bis(diphenylphosphino)ethane)Au2Cl2] [ No CAS ]
[Au₄(1,2-bis(diphenylphosphino)ethane)₂(μ₂-D-pen-κ²S)₂]·12H₂O [ No CAS ]

Reference： [1]Chemistry - An Asian Journal,2018,vol. 13,p. 1906 - 1910

84
[ 52-67-5 ]
[ 455-18-5 ]
(S)-5,5-dimethyl-2-(4-(trifluoromethyl)phenyl)-4,5-dihydrothiazole-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; sodium hydroxide; In methanol; water; at 0 - 45℃; for 8h;	To a stirred solution of <strong>[52-67-5]D-penicillamine</strong> 6 (336 mg, 2.25 mmol), 4-(trifluoromethyl)benzonitrile 7 (257 mg, 1.50 mmol), and sodium bicarbonate (126 mg, 1.50 mmol) were added to a degassed mixture of MeOH/H2O (1.5:1) (5mL), and a catalytic amount of 1M NaOH (1.50 ml) at 0 C. The reaction mixture which remained suspended throughout, was stirred at 45 C for 8 h and was quenched by adding cold water (5 mL). Methanol was then evaporated from the mixture under reduced pressure. The resulting mixture was extracted with EtOAc (4x10 mL), washed with brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude compound 8 was obtained (452 mg, 99%) as a white solid. ESI LC/MS: m/z calcd. for C13H13F3NO2S [M+H]+: 304.06; found 304.10. 1H NMR (CD3OD, 400 MHz) 8.02 (d, J = 8.0Hz, 2H), 7.74 (d, J = 8.01 Hz, 2H), 4.76 (s, 1H), 1.82 (s, 3H), 1.55 (s, 3H). 13C NMR (CD3OD, 100 MHz) 174.25, 167.56, 137.09, 132.48, 132.16, 128.91, 128.46, 127.72, 125.11, 89.25, 61.29, 27.99, 25.42.

Reference： [1]Tetrahedron Letters,2018,vol. 59,p. 4384 - 4386

85
ammonium hexafluorophosphate [ No CAS ]
cobalt(II) chloride hexahydrate [ No CAS ]
[ 52-67-5 ]
[ 7732-18-5 ]
[ 1539-42-0 ]
[Co(D-penicillaminate)(bis(2-pyridylmethyl)amine )]PF₆ monohydrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.14 g		General procedure: To a solution containing DLCl (0.22 g, 0.5 mmol) in a minimumamount of H2O was added NaNO3 (0.90 g, 11 mmol). After the mixturewas allowed to stand at ambient temperature for several days,the resulting brown crystals were collected by filtration. Yield:0.063 g (27% based on Co).

Reference： [1]Inorganica Chimica Acta,2015,vol. 428,p. 127 - 132

86
[ 52-67-5 ]
[ 19194-62-8 ]
(S)-2-(1H-indole-3-carbonyl)-5,5-dimethyl-4,5-dihydrothiazole-4-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97 mg	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 40℃;Inert atmosphere;	l//-indole-3 -carbonyl cyanide (213 mg, 1.252 mmol) and ()-2-amino-3- mercapto-3-methylbutanoic acid (187 mg, 1.252 mmol) were combined with DMF (12 mL) then the mixture treated with l,8-diazabicyclo[5.4.0]undec-7-ene (18.72 m, 0.125 mmol). The reaction mixture was heated to 40 C. Chromatography (silica gel, heptane to EtOAc + 0.1% AcOH) gave 65 -2-( l //-indole-3 -carbonyl )-5,5-di methyl -4,5-dihydrothiazole-4-carboxylic (97 mg) as a white solid, ESI MS m/z 303 [M + H]+. Treatment of the solid with sodium methoxide (16.97 mg, 0.314 mmol) in MeOH (10 ml) gave sodium ()-2-(liT-indole-3- carbonyl)-5,5-dimethyl-4,5-dihydrothiazole-4-carboxylate after the solvent was removed to dryness. The material was used as is.

Reference： [1]Patent: WO2019/99977,2019,A2 .Location in patent: Paragraph 00191; 00225

87
[ 52-67-5 ]
[ 57597-64-5 ]
C₁₉H₂₄N₂O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	In methanol; water; at 0 - 80℃; for 2h;Inert atmosphere;	Specifically, 123 mg (0.50 mmol) of the raw material aldehyde-based coumarin was weighed and added to a mixed solvent of 20 mL of methanol and water (in which the volume ratio of methanol to water was 1:1) to obtain a reaction liquid.Under a N2 protection, <strong>[52-67-5]D-penicillamine</strong> 89 mg (0.60 mmol) was added to the reaction mixture at 0 C, and the reaction was carried out at reflux temperature 80 C for 2 h.The mixed solvent was dried under reduced pressure and the residue was evaporated and evaporated.The organic phases were combined and washed sequentially with 1M hydrochloric acid and saturated sodium chloride.The organic phases were combined, dried over anhydrous sodium sulfate and filtered, and then evaporated.After separation by silica gel column chromatography, the eluent was dichloromethane: methanol: formic acid volume ratio of 60:2:1, and a total of 135 mg of the fluorescent probe I was isolated (72% yield).Show).

Reference： [1]Patent: CN109970730,2019,A .Location in patent: Paragraph 0073-0078

88
[ 1020-31-1 ]
[ 52-67-5 ]
2-(5,7-di-tert-butylbenzo[d]oxazol-2-yl)propane-2-thiol [ No CAS ]

Reference： [1]Advanced synthesis and catalysis,2020,vol. 362,p. 1064 - 1083

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	52-67-5	MDL No. :
Formula :	C₅H₁₁NO₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	-
M.W :	149.21	Pubchem ID :	-
Synonyms :	D-(-)-Penicillamine;NSC 81549;Penicillaminate, Copper;Depen;Cuprimine;3-Mercapto-D-valine;β-Thiovaline;D-Penicillamine	Chemical Name :	(S)-2-Amino-3-mercapto-3-methylbutanoic acid

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.8
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	38.6
TPSA :	102.12 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.47 cm/s

Log Po/w (iLOGP) :	0.85
Log Po/w (XLOGP3) :	-1.78
Log Po/w (WLOGP) :	0.11
Log Po/w (MLOGP) :	-2.2
Log Po/w (SILICOS-IT) :	-0.42
Consensus Log Po/w :	-0.69

[ CAS No. 52-67-5 ] {[proInfo.proName]}

Quality Control of [ 52-67-5 ]

Related Doc. of [ 52-67-5 ]

Product Details of [ 52-67-5 ]

Calculated chemistry of [ 52-67-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 52-67-5 ]

Application In Synthesis of [ 52-67-5 ]

[ 52-67-5 ] Synthesis Path-Upstream 1~1

[ 52-67-5 ] Synthesis Path-Downstream 1~88

Similar Product of
[ 52-67-5 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	0.49
Solubility :	459.0 mg/ml ; 3.08 mol/l
Class :	Highly soluble
Log S (Ali) :	0.15
Solubility :	211.0 mg/ml ; 1.42 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	0.14
Solubility :	207.0 mg/ml ; 1.39 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.83

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335-H351-H361	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

[ CAS No. 52-67-5 ] {[proInfo.proName]}

Quality Control of [ 52-67-5 ]

Related Doc. of [ 52-67-5 ]

Product Details of [ 52-67-5 ]

Calculated chemistry of [ 52-67-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 52-67-5 ]

Application In Synthesis of [ 52-67-5 ]

[ 52-67-5 ] Synthesis Path-Upstream 1~1

[ 52-67-5 ] Synthesis Path-Downstream 1~88

Similar Product of [ 52-67-5 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Similar Product of
[ 52-67-5 ]