140231-31-8

Basic information

• Product Name: 4-MERCAPTO-4-METHYLVALERIC ACID
• Synonyms: 4-MERCAPTO-4-METHYLVALERIC ACID;4-Methyl-4-sulfanylpentanoic acid;Pentanoicacid, 4-mercapto-4-methyl-
• CAS NO: 140231-31-8
• Molecular Formula: C₆H₁₂O₂S
• Molecular Weight: 148.22
• Product Categories: Small molecule
• Mol File: 140231-31-8.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 256.438 °C at 760 mmHg
• Flash Point: 108.89 °C
• Appearance: /
• Density: 1.087 g/cm³
• PKA: 4.60±0.10(Predicted)
• CAS DataBase Reference: 4-MERCAPTO-4-METHYLVALERIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: 4-MERCAPTO-4-METHYLVALERIC ACID(140231-31-8)
• EPA Substance Registry System: 4-MERCAPTO-4-METHYLVALERIC ACID(140231-31-8)

Safety Data

• Hazardous Substances Data: 140231-31-8(Hazardous Substances Data)

Usage

General Description

4-Mercapto-4-methylvaleric acid, also known as L-MMAVA or MMVA, is a type of organic sulfur compound. It's characterized by the presence of a thiol or mercapto group (-SH), and a carboxylic acid group (-COOH). 4-MERCAPTO-4-METHYLVALERIC ACID is often used in scientific research, particularly in biochemistry and pharmacology. It's considered an important metabolite in the metabolism pathway of methionine, a crucial amino acid in humans. Moreover, abnormal levels of 4-mercapto-4-methylvaleric acid in the body can be indicative of certain health conditions including hepatocellular carcinoma, marking its significance in medical diagnostics. However, precise information on its practical applications and safety measures needs to be referenced through specialized scientific resources.

Synthetic route

4-mercapto-4-methylvaleronitrile (131237-84-8) → 4-mercapto-4-dimethylpentanoic acid (140231-31-8)

Conditions	Yield
With sodium hydroxide In ethanol; water Heating / reflux;	39%
With sodium hydroxide In ethanol Heating;	10 g

2,2-dimethylthiirane (3772-13-2) + carbon dioxide (124-38-9) → 4-mercapto-4-dimethylpentanoic acid (140231-31-8)

Conditions	Yield
With sodium hydroxide; n-butyllithium; sodium sulfate In tetrahydrofuran; hydrogenchloride; ethanol; water; ethyl acetate; acetonitrile	39%

4-methyl-3-pentanoic acid → 4-mercapto-4-dimethylpentanoic acid (140231-31-8)

Conditions	Yield
With hydrogen sulfide; sulfur at 180℃;

thiourea (17356-08-0) + methyl 4-hydroxy-4-methylpentanoate (89795-03-9, 7210-38-0) → 4-mercapto-4-dimethylpentanoic acid (140231-31-8)

Conditions	Yield
Stage #1: thiourea; methyl 4-hydroxy-4-methylpentanoate With hydrogenchloride In water for 24h; Reflux; Stage #2: With water; lithium hydroxide In methanol Reflux;

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + 11-amino-3,6,9-trioxaundecanol (86770-74-3) → C14H29NO5S

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 0.533333h; Stage #2: 11-amino-3,6,9-trioxaundecanol In acetonitrile for 18h;	96%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + N-acetyl calicheamicin → 4-(((E)-2-((1R,8S,Z)-8-(((2R,3R,4R,5S,6R)-5-((((2S,4S,5S,6R)-5-((4-(((2S,3R,4R,5S,6S)-3,5-dihydroxy-4-methoxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-3-iodo-5,6-dimethoxy-2-methylbenzoyl)thio)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)amino)-3-(((2S,4S,5S)-5-(N-ethylacetamido)-4-methoxytetrahydro-2H-pyran-2-yl)oxy)-4-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-1-hydroxy-10-((methoxycarbonyl)amino)-11-oxobicyclo[7.3.1]trideca-4,9-dien-2,6-diyn-13-ylidene)ethyl)disulfanyl)-4-methylpentanoic acid

Conditions	Yield
With triethylamine In acetonitrile at -15 - 20℃;	90.5%

2,2'-dipyridyldisulphide (2127-03-9) + 4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 4-(2-pyridylldisulfanyl)-4-methylvaleric acid

Conditions	Yield
With sodium phosphate In methanol for 6h; pH=7.5;	87%
In methanol; aq. phosphate buffer for 6h; pH=7.5;	87%
In methanol; aq. phosphate buffer for 6h; pH=7.5;	87%
In methanol; aq. phosphate buffer for 6h; pH=7.5;	87%

methanethiosulfonic acid S-methyl ester (2949-92-0) + 4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N-methyl-N-[4-methyl-(4-methyldithio)-1-oxopropyl]-L-alanine (796073-55-7)

Conditions	Yield
In methanol at 0 - 20℃; pH=6 - 7.5; aq. phosphate buffer;	83%
With sodium carbonate In ethanol; water at 20℃; for 3h;	70%
With sodium carbonate In ethanol; water at 0℃; for 3h;	70%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + 2-(2-Aminoethoxy)ethanol (929-06-6) → C10H21NO3S

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 0.5h; Stage #2: 2-(2-Aminoethoxy)ethanol In acetonitrile for 20h;	69%
Stage #1: 4-mercapto-4-dimethylpentanoic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane for 0.166667h; Stage #2: 2-(2-Aminoethoxy)ethanol In dichloromethane for 19h;

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + N-BOC-1,2-diaminoethane (57260-73-8) → C13H26N2O3S

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.166667h; Stage #2: N-BOC-1,2-diaminoethane In dichloromethane for 24h;	67%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + tert-butyl N-methyl-N-<2-(methylamino)ethyl>carbamate (112257-19-9) → tert-butyl methyl{2-[methyl(4-methyl-4-sulfanylpentanoyl)amino]ethyl}carbamate

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h; Inert atmosphere;	65%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + C57H77IN4O22S4 → C62H85IN4O24S3

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide; acetonitrile at -15 - 20℃; for 0.5h;	61%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + Propargylamine (2450-71-7) → C9H15NOS

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 1h; Stage #2: Propargylamine In acetonitrile	59%
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 1h; Stage #2: Propargylamine In acetonitrile	59%
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 1h; Stage #2: Propargylamine In acetonitrile	59%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + benzylamine (100-46-9) → C13H19NOS

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 1h; Stage #2: benzylamine In acetonitrile	59%
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile for 1h; Stage #2: benzylamine In acetonitrile	59%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + 2-(2-(Pyridin-2-yl)disulfanyl)ethanol (111625-28-6) → 4-((2-hydroxyethyl)disulfanyl)-4-methylpentanoic acid

Conditions	Yield
With acetic acid In methanol at 45℃; for 120h;	58.1%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + 2-(2-methoxyethoxy)ethanamine (31576-51-9) → C11H23NO3S

Conditions	Yield
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In chloroform at 20 - 60℃; for 75.5h;	54%

4-((2-pyridyl)dithio)butan-1-ol (892402-95-8) + 4-mercapto-4-dimethylpentanoic acid (140231-31-8) → C10H20O3S2

Conditions	Yield
With acetic acid In methanol at 20℃; for 16h;	50%
With acetic acid In methanol at 20℃; for 16h;	50%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + C15H23NO2 → C21H33NO3S

Conditions	Yield
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: C15H23NO2 In acetonitrile at 20℃;	49%
Stage #1: 4-mercapto-4-dimethylpentanoic acid With dmap; acetic anhydride; triethylamine In acetonitrile at 20℃; for 0.5h; Inert atmosphere; Stage #2: C15H23NO2 In acetonitrile at 20℃;	49%

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 4,4,7,7-tetramethyl-5,6-dithia-decanedioic acid

Conditions	Yield
With iodine

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N-methyl-N-[4-methyl-(4-methyldithio)-1-oxopentyl]-L-alanine (796073-57-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 2,5-dioxopyrrolidin-1-yl 4-methyl-4-(methyldisulfanyl)pentanoate (796073-56-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N2′-deacetyl-N2′-(4-mercapto-4-methyl-1-oxopentyl)maytansine (796073-69-3)

Conditions

Yield

Multi-step reaction with 5 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h 4: 36 percent / dicyclohexylcarbodiimide; ZnCl2 / CH2Cl2; diethyl ether / 2 h / 20 °C 5: 97 percent / dithiothreitol / methanol; ethyl acetate; aq. phosphate buffer / 3 h / pH 7.5 View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → D-N2'-deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)maytansine

Conditions	Yield
Multi-step reaction with 5 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h 4: dicyclohexylcarbodiimide; ZnCl2 / CH2Cl2; diethyl ether / 2 h / 20 °C 5: dithiothreitol; EDTA / methanol; ethyl acetate; aq. phosphate buffer / 20 °C / pH 7.5 View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N2'-deacetyl-N2'-[4-methyl-4-(methyldithio)-1-oxopentyl]maytansine (796073-68-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h 4: 36 percent / dicyclohexylcarbodiimide; ZnCl2 / CH2Cl2; diethyl ether / 2 h / 20 °C View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N2'-deacetyl-N2'-[4-methyl-4-(methyldithio)-1-oxopentyl]-D-maytansine (902768-55-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h 4: dicyclohexylcarbodiimide; ZnCl2 / CH2Cl2; diethyl ether / 2 h / 20 °C View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → N2'-deacetyl-N2'-[4-methyl-4-(3-carboxy-propyldithio)-1-oxopentyl]maytansine

Conditions

Yield

Multi-step reaction with 6 steps 1: 70 percent / sodium carbonate / ethanol; H2O / 3 h / 20 °C 2: 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide*HCl / CH2Cl2 / 2 h 3: triethylamine / H2O; 1,2-dimethoxy-ethane / 2 h 4: 36 percent / dicyclohexylcarbodiimide; ZnCl2 / CH2Cl2; diethyl ether / 2 h / 20 °C 5: 97 percent / dithiothreitol / methanol; ethyl acetate; aq. phosphate buffer / 3 h / pH 7.5 6: 57 percent / EDTA / methanol; aq. phosphate buffer / 3 h / pH 7.6 View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) + 5,5'-dinitro-2,2'-disulfanediyl-bis-pyridine (2127-10-8) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 4-methyl-4-(5-nitro-pyridin-2-yldithio)pentanoic Acid (663598-96-7)

Conditions	Yield
With 4-methyl-morpholine In tetrahydrofuran; ethyl acetate

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 1-(1S)-(chloromethyl)-5-hydroxy-3-{5-[(5-(4-(methyldisulfanyl)-3,3-dimethylbutyryl)indol-2-ylcarbonyl)amino]indole-2-carbonyl}-1,2-dihydro-3H-benz[e]indole (1354787-71-5)

Conditions	Yield
Multi-step reaction with 4 steps 1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere 3: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 4: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → t-butyl 5-[5-(4-methyldithio-3,3-dimethylbutyryl)indol-2-yl-carbonylamino]indole-2-carboxylate (1354787-73-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 5-[5'-(3-(methyldithio)-3,3-dimethyl butyryl)indol-2-ylcarbonylamino]indole-2-carboxylic acid (1354787-74-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere 3: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h View Scheme

4-mercapto-4-dimethylpentanoic acid (140231-31-8) → 1-[S]-(chloromethyl)-5-phosphonoxy-3-{{5-[5-(4-methyldithio-3,3-dimethylbutyryl)indol-2-ylcarbonylamino]indole-2-yl}-carbonyl}-1,2-dihydro-3H-benz[e]indole (1354787-76-0)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2.1: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere 3.1: triethylsilane; trifluoroacetic acid / dichloromethane / 1 h 4.1: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere 5.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / tetrahydrofuran; acetonitrile / 2.5 h / 0 °C / Inert atmosphere 5.2: pH 7 / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: methanol / 0 - 20 °C / pH 6 - 7.5 / aq. phosphate buffer 2.1: N,N-dimethyl acetamide; 1,2-dichloro-ethane / Inert atmosphere 3.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / tetrahydrofuran; acetonitrile / 2.5 h / 0 °C / Inert atmosphere 3.2: pH 7 / Inert atmosphere View Scheme

Upstream product

• 17356-08-0 thiourea 
• 89795-03-9 methyl 4-hydroxy-4-methylpentanoate 
• 3772-13-2 2,2-dimethylthiirane 
• 124-38-9 carbon dioxide 
• 131237-84-8 4-mercapto-4-methylvaleronitrile 

Downstream Products

• 890409-85-5 4-(2-pyridinedisulfide)-4-methylvaleric acid succinimide ester 
• 1354787-75-9 C₅₂H₄₉ClN₅O₇PS₂ 
• 796073-68-2 N^2'-deacetyl-N^2'-[4-methyl-4-(methyldithio)-1-oxopentyl]maytansine 
• 796073-69-3 N^2′-deacetyl-N^2′-(4-mercapto-4-methyl-1-oxopentyl)maytansine 

Relevant articles and documents

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Semisynthetic Maytansine analogues for the targeted treatment of cancer

Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.

Cytotoxic agents comprising new maytansinoids

New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the α-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.