4478-93-7

Basic information

• Product Name: DL-SULFORAPHANE
• Synonyms: sulforafan;sulforaphan;sulforaphane;R-SULFORAPHANE;R,S-SULFORAPHANE;SULFORAPHANE, L-;SULFORAPHANE, DL-;SULFORAPHANE, D-
• CAS NO: 4478-93-7
• Molecular Formula: C₆H₁₁NOS₂
• Molecular Weight: 177.29
• Product Categories: Sulphur Derivatives;Miscellaneous Natural Products;All Inhibitors;Inhibitors;Sulfur & Selenium Compounds;Antitumour;Aliphatics
• Mol File: 4478-93-7.mol
• Article Data: 26

Chemical Properties

• Boiling Point: 125-135°C
• Flash Point: 176.5 °C
• Appearance: slightly yellow/liquid
• Density: 1.17 g/cm³
• Storage Temp.: −20°C
• Solubility: DMSO: 40 mg/mL, soluble
• Stability: Light Sensitive
• CAS DataBase Reference: DL-SULFORAPHANE(CAS DataBase Reference)
• NIST Chemistry Reference: DL-SULFORAPHANE(4478-93-7)
• EPA Substance Registry System: DL-SULFORAPHANE(4478-93-7)

Safety Data

• Safety Statements: 23-24/25
• WGK Germany: 3
• Hazardous Substances Data: 4478-93-7(Hazardous Substances Data)

Usage

Description

Sulforaphane is a compound within the isothiocyanate group of organosulfur compounds and mainly found in cruciferous vegetables. It is produced when the enzyme myrosinase transforms glucoraphanin,a prodrug or storage form of SFN, into SFN upon damage to the plant (such as from chewing),which allows the two compounds to mix and react. Glucoraphanin is one of a few molecules known as isothiocyanates, existing alongside Sinigrin (metabolized into allylisothiocyanate).

Chemical Properties

DL-Sulforaphane (SFN) is a slightly yellow liquid. soluble in DMSO, methanol, or water-like solvents. SFN exists in food in its food-bound form known as Glucoraphanin. It is present in a wide range of vegetables such as cabbage, cauliflower, bok choy, kale, chinese broccoli, mustard, turnip, radish, and watercress.

Uses

Potent, selective inducer of phase II detoxification enzymes with anticarcinogenic properties. Occurs naturally in broccoli. It was found to inhibit chemically induced mammary tumor formation in rats. Antitumor agentLNCaP prostate cancer cells were treated with DL-Sulforaphane to study the effect on androgen receptor. Effects on malathion toxicity was studied in rats by treating them with DL-Sulforaphane.Nrf2 activation of the antioxidant response element (ARE) is central to cytoprotective gene expression against oxidative and/or electrophilic stress.Unless activated by inflammatory, environmental, or oxidative stressors, Nrf2 is sequestered in the cytoplasm by its repressor, Keap1.Because of its protective capabilities, small molecules that activate Nrf2 signaling are being examined as potential anti-cancer or anti-inflammatory agents.Sulforaphane is an isothiocyanate derived from cruciferous vegetables, including broccoli, that potently induces chemopreventative enzymes via Keap1-Nrf2 signaling and ARE-driven gene expression.At 15 μM, sulforaphane inhibits class I and II HDAC activity and suppresses tumor growth by inducing cell cycle arrest and apoptosis selectively in various cancerous prostate epithelial cells without affecting normal cells.Differential effects of sulforaphane on histone deacetylases, cell cycle arrest and apoptosis in normal prostate cells versus hyperplastic and cancerous prostate cells

Definition

ChEBI: Sulforaphane is an isothiocyanate having a 4-(methylsulfinyl)butyl group attached to the nitrogen. It has a role as an antineoplastic agent, a plant metabolite, an antioxidant and an EC 3.5.1.98 (histone deacetylase) inhibitor. It is a sulfoxide and an isothiocyanate.

benefits

Sulforaphane(SFN) promotes detoxification,prevents and combats cancer,lowers cholesterol,improves diabetes, can boost the immune system, is antiviral, antibacterial, and antifungal, combats inflammation,protect skin,eyes,kidneys, and brain, and restores its cognitive function. Deep insight in several studies has reported that dietary intake of cruciferous vegetables has a direct association in the decline in the incidence of various tumors such as prostate, cervical, ovarian, and lung cancer. It improves the liver function, attenuates pain, improves hair growth,promotes bone formation, and prevents muscle damage.SFN treatment reducesDNA damage and mutation rate when cancer-causing chemicals bind DNA.Although an ideal dosage is not known, the dietary addition of 0.1-0.5mg/kg SFN to rats has been noted to be bioactive. This is an estimated human dose of 7-34mg for a 1501b person; 9-45mg for a 2001b person; 11-57mg for a 250lb person.

General Description

An isothiocyanate isolated from broccoli that acts as a potent inducer of phase II detoxifying enzymes in mouse tissues and murine hepatoma cells in culture. It has been shown to be an effective agent in prevention of chemically-induced mammary tumors in rats. It also inhibits the phase I cytochrome P450 isoenzymes 2E1 and IA2 which have been associated with the activation of carcinogens. The induction of phase II enzymes is mediated by mitogen-activated protein kinase (MAPK) pathway.

Biological Activity

Selective inducer of phase II detoxification enzymes with anticarcinogenic properties. Organosulfur compound found in cruciferous vegetables, including broccoli.Sulforaphane is an anti-cancer, anti-microbial and anti-diabetic compound found in cruciferous vegetables. It induces the production of detoxifying enzymes such as quinone reductase and glutathione S-transferase that cause xenobiotic transformation. Sulforaphane also increases the transcription of tumor suppressor proteins and inhibits histone deacetylases. It modulates inflammatory responses by suppressing the LPS-mediated expression of iNOS, COX-2, IL-1β and TNF-α.

Anticancer Research

Sulforaphane is an isothiocyanate compound found in cruciferous vegetables like broccoli,Brussels sprouts, and cabbages. It induces phase II drug metabolism enzymes ofxenobiotic transformation and enhances the transcription of tumor suppressionproteins. It promotes cytotoxicity in p53-deleted colon cancer cells by mitochondriaandlysosome-dependent cell death. Due to the effect of sulforaphane, Bax is alsobeing increased in the presence of inhibition of JNK-induced Bcl-2 followed bymitochondrial cytochrome-C release and activation of apoptosis. Self-renewal Wnt/β-catenin signaling pathway is downregulated by sulforaphane in breast cancer stemcells. It has been reported to inhibit the activity of histone deacetylase (HDAC) andto reduce the number of polyps in Apcmin/+ mouse by inhibiting AKT and ERKsignaling and protein expression of COX-2 and cyclin-D1. Sulforaphane alsoinhibits the growth of SW620 cells by inducing apoptosis (Clarke et al. 2008). Inhuman colon cancer cells (HT-29), sulforaphane showed increased dose-dependentluciferase activity of AP-1, induced JAK activity, and inhibited NF-κB luciferaseactivation induced by LPS. It is also reported to inhibit cellular proliferation and toinduce apoptosis. In HepG2 human hepatoma cells, sulforaphane significantlyinduces the expression of the Nrf-2 protein and activation of ARE-mediatedtranscription, delays Nrf-2 degradation by inhibition of Keap1, and activates theexpression of transcription of the antioxidant HO-1 enzyme. This activation of thetranscription is partially modulated by the signaling pathway of p38 MAPK, whilep38 MAPK phosphorylates Nrf-2 and improves the binding between the proteinsNrf-2 and Keap1. In the PC-3 cells of human prostate cancer, sulforaphanesuppresses the expression regulated by NF-κB and NF-κB signaling pathway by theIκBα and IKK pathways (Wang et al. 2012).

references

[1] gamet-payrastre l, li p, lumeau s, et al. sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in ht29 human colon cancer cells[j]. cancer research, 2000, 60(5): 1426-1433.[2] kansanen e, kuosmanen s m, leinonen h, et al. the keap1-nrf2 pathway: mechanisms of activation and dysregulation in cancer[j]. redox biology, 2013, 1(1): 45-49.

InChI:InChI=1/C6H11NOS2/c1-10(8)5-3-2-4-7-6-9/h2-5H2,1H3

Synthetic route

erucin (4430-36-8) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 0.5h;	100%
With dihydrogen peroxide In methanol	100%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at -5℃; for 3h;	95%

thiophosgene (463-71-8) + (+/-)-1-amino-4-(methylsulfinyl)butane (84104-30-3) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With sodium hydroxide In chloroform; water for 1h;	85.7%
With sodium hydroxide In chloroform for 0.583333h;	57%
With sodium hydroxide In chloroform at 20℃; for 1h;	52%
With sodium hydrogencarbonate In dichloromethane

carbon disulfide (75-15-0) + (+/-)-1-amino-4-(methylsulfinyl)butane (84104-30-3) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Stage #1: carbon disulfide; (+/-)-1-amino-4-(methylsulfinyl)butane With triethylamine In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: With dmap; di-tert-butyl dicarbonate In ethanol at 0 - 20℃; for 2.25h;	79%

3-Chloropropyl isothiocyanate (2799-72-6) + sodium methylsulfinylmethanide (15590-23-5) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
In tetrahydrofuran at -30℃; for 3h; Solvent; Temperature;	64.7%

4-methylsulfinylbutyl glucosinolate → D-Glucose (2280-44-6) + D,L-sulforaphane (4478-93-7)

Conditions	Yield
With myrosinase; buffer pH = 6.5 at 37℃;

methyl-<4-amino-butyl>-sulfoxide → D,L-sulforaphane (4478-93-7)

sulforaphane cysteine → L-Cysteine (52-90-4) + D,L-sulforaphane (4478-93-7)

Conditions	Yield
In water; dimethyl sulfoxide at 37℃; pH=7.4; Kinetics; Product distribution; Further Variations:; pH-values;

C11H20N2O5S3 → D,L-sulforaphane (4478-93-7) + N-acetyl-L-cysteine

Conditions	Yield
In water; dimethyl sulfoxide at 37℃; pH=7.4; Kinetics; Product distribution; Further Variations:; pH-values;

(11R,16S)-16-amino-11-((carboxymethyl)carbamoyl)-13-oxo-8-methylsulfinyl-2,9-dithia-7,12-diazaheptadecan-17-oic acid → D,L-sulforaphane (4478-93-7) + GLUTATHIONE (70-18-8)

Conditions	Yield
In water; dimethyl sulfoxide at 37℃; pH=7.4; Kinetics; Product distribution; Further Variations:; pH-values;

4-methylsulfinylbutyl glucosinolate → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With phosphate buffer; myrosinase at 37℃; pH=6.5;

4-(methylthio)-1-butylamine (55021-77-7) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 12.5 mmol / sodium hydroxide / CHCl3 2: 100 percent / m-chloroperbenzoic acid / CH2Cl2 / 0.5 h View Scheme
Multi-step reaction with 2 steps 1: 64 percent / aq. H2O2; H2SO4; i-PrOH / methanol / 2 h / 20 °C 2: 57 percent / aq. NaOH / CHCl3 / 0.58 h View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid; dihydrogen peroxide / methanol; water; isopropyl alcohol / 3 h / 20 °C 2: sodium hydroxide / chloroform / 1 h / 20 °C View Scheme

2-<2-(Methylthio)butyl>-1H-isoindole-1,3(2H)-dione (52096-68-1) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 21.1 mmol / hydrazine monohydrate; hydrogen chloride / ethanol / 2 h / 75 °C 2: 12.5 mmol / sodium hydroxide / CHCl3 3: 100 percent / m-chloroperbenzoic acid / CH2Cl2 / 0.5 h View Scheme
Multi-step reaction with 3 steps 1.1: hydrazine hydrate / methanol / 70 °C 2.1: triethylamine / tetrahydrofuran / 0 - 20 °C 2.2: 0.5 h / 0 - 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.08 h / -10 - 0 °C View Scheme
Multi-step reaction with 3 steps 1: hydrazine hydrate / ethanol / 3 h / Reflux 2: sodium hydroxide / dichloromethane / 3.5 h / 0 - 20 °C / Inert atmosphere 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 2 h / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: acetic acid; dihydrogen peroxide 2: hydrazine hydrate / ethanol / Reflux 3: sodium hydrogencarbonate / dichloromethane View Scheme

4-(methylthio)butyronitrile (59121-24-3) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 63 percent / BH3 / tetrahydrofuran / 20 °C 2: 64 percent / aq. H2O2; H2SO4; i-PrOH / methanol / 2 h / 20 °C 3: 57 percent / aq. NaOH / CHCl3 / 0.58 h View Scheme
Multi-step reaction with 3 steps 1: lithium aluminium tetrahydride / diethyl ether / 0.5 h / Reflux 2: sulfuric acid; dihydrogen peroxide / methanol; water; isopropyl alcohol / 3 h / 20 °C 3: sodium hydroxide / chloroform / 1 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: lithium aluminium tetrahydride / diethyl ether / 3 h / Inert atmosphere; Reflux 2.1: dihydrogen peroxide / 2,2,2-trifluoroethanol / 1.33 h / 0 - 20 °C / Inert atmosphere 3.1: triethylamine / ethanol / 0.5 h / 20 °C / Inert atmosphere 3.2: 2.25 h / 0 - 20 °C View Scheme

thiophosgene (463-71-8) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Stage #1: 4-(methylthio)-1-butylamine With dihydrogen peroxide In water; acetone at 50℃; Stage #2: thiophosgene With sodium hydroxide In dichloromethane; water; acetone for 0.5h;

4-(methylsulfinyl)butyl-glucosinolate (21414-41-5) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With myrosinase; water

tert-butyl [4-(methylsulfanyl)butyl]carbamate (1350472-27-3) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: hydrogenchloride / dichloromethane / 2 h / 20 °C 2.1: triethylamine / tetrahydrofuran / 1.5 h / 0 - 20 °C 2.2: 0.5 h / 0 - 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.42 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride / dichloromethane / 2 h / 20 °C 2: triethylamine / dichloromethane / 12 h / 0 - 20 °C 3: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.42 h / 0 °C View Scheme

4-(methylsulfanyl)butan-1-amine hydrochloride → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triethylamine / tetrahydrofuran / 1.5 h / 0 - 20 °C 1.2: 0.5 h / 0 - 20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.42 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine / dichloromethane / 12 h / 0 - 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 1.42 h / 0 °C View Scheme

(R,S)S-glucoraphanin → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With myrosinase In aq. phosphate buffer pH=7.2; Enzymatic reaction;

1-[5-(methylsulfinyl)-N-(sulfonatooxy)pentanimidoyl]-1-thio-β-D-glucopyranose → D,L-sulforaphane (4478-93-7)

Conditions	Yield
With ascorbic acid at 38℃; for 0.5h; pH=7.5; Reagent/catalyst; Enzymatic reaction;	120.16 μmol

S-methyltetrahydrothiophenium fluoroborate → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium azide / N,N-dimethyl-formamide / 16 h / 60 °C / Green chemistry 2.1: triphenylphosphine / diethyl ether / 3 h / 20 °C / Green chemistry 2.2: 1 h / 20 °C / Green chemistry 3.1: dihydrogen peroxide; acetic acid / 1 h / 20 °C / Green chemistry View Scheme
Multi-step reaction with 3 steps 1.1: sodium azide / N,N-dimethyl-formamide / 16 h / 60 °C 2.1: triphenylphosphine / diethyl ether / 3 h / 20 °C 2.2: 1 h / 20 °C 3.1: dihydrogen peroxide; acetic acid / 1 h / 20 °C View Scheme

1-azido-(4-methylsulfenyl)butane (57775-01-6) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: triphenylphosphine / diethyl ether / 3 h / 20 °C / Green chemistry 1.2: 1 h / 20 °C / Green chemistry 2.1: dihydrogen peroxide; acetic acid / 1 h / 20 °C / Green chemistry View Scheme

4-(methylthio)-1-butanol (20582-85-8) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 1 h / -10 - 20 °C 2.1: sodium azide; tetrabutylammomium bromide / acetone; water / 6 h / Reflux; Inert atmosphere 3.1: triphenylphosphine / toluene / 4 h / 0 - 20 °C / Inert atmosphere 3.2: 24 h / 20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / -5 °C View Scheme

4-methylthio-1-butyl methanesulfonate → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: sodium azide; tetrabutylammomium bromide / acetone; water / 6 h / Reflux; Inert atmosphere 2.1: triphenylphosphine / toluene / 4 h / 0 - 20 °C / Inert atmosphere 2.2: 24 h / 20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 3 h / -5 °C View Scheme

N-(4-methanesulfinyl-butyl)-phthalimide (163956-72-7) → D,L-sulforaphane (4478-93-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / Reflux 2: sodium hydrogencarbonate / dichloromethane View Scheme

tyrosamine (51-67-2) + D,L-sulforaphane (4478-93-7) → C14H22N2O2S2

Conditions	Yield
In N,N-dimethyl-formamide at 20℃; for 10h; Inert atmosphere;	98.62%

(+/-)-1-amino-4-(methylsulfinyl)butane (84104-30-3) + D,L-sulforaphane (4478-93-7) → N,N’-di-(4-methylsulfinylbutyl)thiourea

Conditions	Yield
In dichloromethane for 1h; Reflux;	97%

1-methyl-piperazine (109-01-3) + D,L-sulforaphane (4478-93-7) + dichloromethane (75-09-2) → 4-methyl-N-(4-(methylsulfinyl)-butyl)piperazine-1-carbothioamide (1356472-66-6)

Conditions	Yield
In dichloromethane for 1h; Reflux;	97%

morpholine (110-91-8) + D,L-sulforaphane (4478-93-7) → N-(4-(methylsulfinyl)butyl)-morpholine-4-carbothioamide (1356346-82-1)

Conditions	Yield
In dichloromethane for 1h; Reflux;	95%

4-amino-1-benzylpiperidine (50541-93-0) + D,L-sulforaphane (4478-93-7) → 1-(1-benzyl-piperidin-4-yl)-3-4-(methylsulfinyl)butyl thiourea (1356346-85-4)

Conditions	Yield
In dichloromethane for 1h; Reflux;	93%

D,L-sulforaphane (4478-93-7) + p-methoxybenzylmercaptan (6258-60-2) → 4-methoxybenzyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	91.9%

D,L-sulforaphane (4478-93-7) + (4-chlorophenyl)methanethiol (6258-66-8) → p-chlorobenzyl N-[4-(methylsulfinyl)butyl]carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	91.8%

D,L-sulforaphane (4478-93-7) + vanillylamine hydrochloride (7149-10-2) → C14H22N2O3S2

Conditions	Yield
Stage #1: vanillylamine hydrochloride With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.166667h; Inert atmosphere; Stage #2: D,L-sulforaphane In N,N-dimethyl-formamide at 20℃; for 10h;	89%

D,L-sulforaphane (4478-93-7) + C8H17NO2S → C14H28N2O3S3

Conditions	Yield
With dmap In dichloromethane at 20℃; for 10h; Inert atmosphere;	88.7%

D,L-sulforaphane (4478-93-7) + ethanethiol (75-08-1) → ethyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; for 5h;	87.5%
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	87.5%

ethanol (64-17-5) + D,L-sulforaphane (4478-93-7) → O-ethyl 4-(methylsulfinyl)butylcarbamothioate (1356472-67-7)

Conditions	Yield
Reflux; Inert atmosphere;	84%

D,L-sulforaphane (4478-93-7) + para-thiocresol (106-45-6) → p-tolyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	83.3%

2-mercaptophenylethane (4410-99-5) + D,L-sulforaphane (4478-93-7) → phenethyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	81.1%

D,L-sulforaphane (4478-93-7) + L-lysine-[(13)C6(15)N2] hydrochloride → N6-({[3-(methylsulfinyl)butyl]amino}carbonothioyl)[(13)C6(15)N2]lysine

Conditions	Yield
Stage #1: L-lysine-[(13)C6(15)N2] hydrochloride With copper(II) carbonate; sodium hydroxide In water at 100℃; for 0.333333h; Stage #2: D,L-sulforaphane In 1,4-dioxane; water at 20℃; for 4h; Stage #3: With sodium sulfide In 1,4-dioxane; water at 20℃; for 0.166667h;	81%

D,L-sulforaphane (4478-93-7) + alpha cyclodextrin (10016-20-3) → sulforaphane-cyclodextrin complex (1498229-87-0)

Conditions	Yield
Stage #1: alpha cyclodextrin In water at 55℃; Inert atmosphere; Cooling with ice; Stage #2: D,L-sulforaphane In water at 20℃; for 16h;	78.5%

D,L-sulforaphane (4478-93-7) + 3-(perfluorophenyl)-1,4,2-dioxazole-5-one → C13H11F5N2O2S2

Conditions	Yield
With carbonyl(5,10,15,20-tetraphenylporphyrinato)ruthenium(II) In toluene at 20℃; for 4h;	76%

1-methyl-1-propanethiol (513-53-1) + D,L-sulforaphane (4478-93-7) → sec-butyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	75%

D,L-sulforaphane (4478-93-7) + 4-t-butylbenzenethiol (2396-68-1) → 4-(tert-butyl)phenyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	72.8%

D,L-sulforaphane (4478-93-7) + 4-methylbenzylthiol (4498-99-1) → 4-methylbenzyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	72.3%

D,L-sulforaphane (4478-93-7) + Methyl 3-mercaptopropionate (2935-90-2) → methyl 3-(((4-(methylsulfinyl)butyl)carbamothioyl)thio)propanoate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	70.8%

D,L-sulforaphane (4478-93-7) + N-acetylcystein (616-91-1) → N-acetyl-S-{N-[4-(methylsulfinyl)butyl]thiocarbamoyl}-L-cysteine

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water	69.5%
With sodium hydroxide In ethanol; water at 23℃; for 2h; pH=7 - 8;	36%

D,L-sulforaphane (4478-93-7) → erysolin (504-84-7)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at -20 - 20℃; for 3h; Inert atmosphere;	66%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane for 2h;	60%

D,L-sulforaphane (4478-93-7) + C8H19NO2S → C14H30N2O3S3

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 10h; Inert atmosphere;	64.5%
With triethylamine In dichloromethane at 20℃; for 10h; Inert atmosphere;	64.5%

D,L-sulforaphane (4478-93-7) + 2-mercapto-pentan-3-one (17042-24-9) → 3-oxopentan-2-yl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	63.6%

4-Methoxybenzenethiol (696-63-9) + D,L-sulforaphane (4478-93-7) → 4-methoxyphenyl (4-(methylsulfinyl)butyl)carbamodithioate

Conditions	Yield
With sodium hydrogencarbonate In ethanol; water at 20℃; Inert atmosphere;	63.2%

Upstream product

• 463-71-8 thiophosgene 
• 84104-30-3 (+/-)-1-amino-4-(methylsulfinyl)butane 
• 21414-41-5 4-(methylsulfinyl)butyl-glucosinolate 
• 1350472-27-3 tert-butyl [4-(methylsulfanyl)butyl]carbamate 
• 163956-72-7 N-(4-methanesulfinyl-butyl)-phthalimide 
• 2799-72-6 3-Chloropropyl isothiocyanate 
• 15590-23-5 sodium methylsulfinylmethanide 
• 20582-85-8 4-(methylthio)-1-butanol 
• 57775-01-6 1-azido-(4-methylsulfenyl)butane 
• 75-15-0 carbon disulfide 
• 59121-24-3 4-(methylthio)butyronitrile 
• 52096-68-1 2-<2-(Methylthio)butyl>-1H-isoindole-1,3(2H)-dione 
• 55021-77-7 4-(methylthio)-1-butylamine 
• 4430-36-8 erucin 

Downstream Products

• 289-16-7 1,2,4-trithiolane 
• 2949-92-0 methanethiosulfonic acid S-methyl ester 
• 13882-12-7 S-methyl methanethiosulfinate 
• 51598-96-0 4-methylsulfanyl-3-butenyl isothiocyanate 
• 334829-66-2 sulforaphane-N-acetyl-cysteine 
• 504-84-7 erysolin 
• 3386-97-8 4-isothiocyanato-1-butene 
• 289711-21-3 (11R,16S)-16-amino-11-((carboxymethyl)carbamoyl)-13-oxo-8-methylsulfinyl-2,9-dithia-7,12-diazaheptadecan-17-oic acid 

Relevant articles and documents

Anti-inflammatory and anti-apoptotic effects of (RS)- glucoraphanin bioactivated with myrosinase in murine sub-acute and acute MPTP-induced Parkinson's disease

This study was focused on the possible neuroprotective role of (R S)-glucoraphanin, bioactivated with myrosinase enzyme (bioactive RS-GRA), in an experimental mouse model of Parkinson's disease (PD). RS-GRA is one of the most important glucosinolates, a thiosaccharidic compound found in Brassicaceae, notably in Tuscan black kale seeds. R S-GRA was extracted by one-step anion exchange chromatography, further purified by gel-filtration and analyzed by HPLC. Following, pure R S-GRA was characterized by 1H and 13C NMR spectrometry and the purity was assayed by HPLC analysis of the desulfo-derivative according to the ISO 9167-1 method. The obtained purity has been of 99%. To evaluate the possible pharmacological efficacy of bioactive RS-GRA (administrated at the dose of 10 mg/kg, ip +5 μl/mouse myrosinase enzyme), C57BL/6 mice were used in two different sets of experiment (in order to evaluate the neuroprotective effects in different phases of the disease), according to an acute (2 injections·40 mg/kg MPTP) and a sub-acute (5 injections·20 mg/kg MPTP) model of PD. Behavioural test, body weight changes measures and immunohistochemical localization of the main PD markers were performed and post-hoc analysis has shown as bioactive R S-GRA is able to reduce dopamine transporter degradation, tyrosine hydroxylase expression, IL-1β release, as well as the triggering of neuronal apoptotic death pathway (data about Bax/Bcl-2 balance and dendrite spines loss) and the generation of radicalic species by oxidative stress (results focused on nitrotyrosine, Nrf2 and GFAP immunolocalization). These effects have been correlated with the release of neurotrophic factors, such as GAP-43, NGF and BDNF, that, probably, play a supporting role in the neuroprotective action of bioactive RS-GRA. Moreover, after PD-induction mice treated with bioactive RS-GRA are appeared more in health than animals that did not received the treatment both for phenotypic behaviour and for general condition (movement coordination, presence of tremors, nutrition). Overall, our results suggest that bioactive RS-GRA can protect neurons against the neurotoxicity involved in PD via an anti-apoptotic/anti-inflammatory action.

A new and effective approach to the synthesis of sulforaphane

Background: Sulforaphane [1-isothiocyanato-(4-methylsulfinyl)butane] identified from appears to possess health benefits such as activities against breast, skin and prostate cancer and diabetes. and studies provide evidence that it can provide protection at every stage of cancer progression. Sulforaphane was firstly synthesized by Von Schmidt and P.Karrer in 1948 via phthalimide route but after Zhang and co-worker reported its bioactivity in 1992, the chemical synthesis of sulforaphane by alternate route has attracted several research groups in the past 20 years . Methods: The synthesis started with the preparation of-methylthiolanium tetrafluoroborate by sonication of thiolane (1) with methyl iodide followed by anionic metathesis with NaBF4 in-butanol to give thiolanium tetrafluorborate (2). The ring opening of 2 by SN2 is conducted in 16 hours at 60 oC (as indicated by TLC) to obtain 1-Azido-(4-methylsulfinyl)butane (3). Conversion 3 into Erucin (4) was successfully obtained by Staudinger reaction, followed by oxidation of 4 in transition metal-free condition (H2O2/ glacial acetic acid) to give sulforaphane in racemic form. Results: Sulforaphane was obtained with 41% yield overall via only four steps with high purity without column chromatography. The approach not only opened up a new synthetic pathway to this naturally occurring isothiocyanate and its analogues, but also suggested a possible solution for converting by-products in petroleum refining processes into useful compounds. Conclusion: Sulforaphane was successfully synthesized from thiolane, a waste product in petroleum processing in a simpler and more efficient fashion, eco-friendy approach. All products were obtained in high yield and high purity. In comparison with previously reported strategies, this new approach is believed to be the shortest and the most efficient synthetic route to date.

Antioxidant activity of two edible isothiocyanates: Sulforaphane and erucin is due to their thermal decomposition to sulfenic acids and methylsulfinyl radicals

Sulforaphane (SFN) and erucin (ERN) are isothiocyanates (ITCs) bearing, respectively, methylsulfinyl and methylsulfanyl groups. Their chemopreventive and anticancer activity is attributed to ability to modulate cellular redox status due to induction of Phase 2 cytoprotective enzymes (indirect antioxidant action) but many attempts to connect the bioactivity of ITCs with their radical trapping activity failed. Both ITCs are evolved from their glucosinolates during food processing of Cruciferous vegetables, therefore, we studied antioxidant behaviour of SFN/ERN at elevated temperature in two lipid systems. Neither ERN nor SFN inhibit the oxidation of bulk linolenic acid (below 100 °C) but both ITCs increase oxidative stability of soy lecithin (above 150 °C). On the basis of GC-MS analysis we verified our preliminary hypothesis (Antioxidants 2020, 9, 1090) about participation of sulfenic acids and methylsulfinyl radicals as radical trapping agents responsible for the antioxidant effect of edible ITCs during thermal oxidation of lipids at elevated temperatures (above 140 °C).

Conversion synthetic method of sulforaphane

The invention relates to a conversion synthetic method of sulforaphane and belongs to the field of organic compound synthesis technology. In order to solve the problem that existing sulforaphane preparation methods have disadvantages of low yield, high cost, toxic raw materials, etc., the invention provides a conversion synthetic method of sulforaphane. The method of the invention comprises the following steps: dimethyl sulfoxide and sodium hydride react according to a certain molar ratio to synthesize methylsulfinyl sodium; 1-bromo-3-chloropropane and thiocyanate react according to a certainmolar ratio to synthesize 3-chloroisothiocyanopropane; and 3-chloroisothiocyanopropane and methylsulfinyl sodium react according to a certain molar ratio to synthesize sulforaphane. By directly bridging two intermediates, one-step synthesis of sulforaphane is realized. The raw materials are safe and stable, and yield is higher. In addition, reaction conditions in the sulforaphane synthesis steps are mild; the reactions can be rapidly carried out in a normal-temperature or low-temperature environment; the synthetic product is avoided from being decomposed by heating; and purity and environmental stability of the product are enhanced. The above beneficial effects are all beneficial to practical application of sulforaphane.

Chemical synthesis method for sulforaphane

The invention discloses a chemical synthesis method for sulforaphane. The method is characterized by including the steps of: (a) taking sodium iodide as the catalyst, reacting 4-chloro-1-butanol with sodium methyl mercaptide to obtain 4-methylthio-1-butanol; (b) in the presence of alkali, reacting 4-methylthio-1-butanol with methylsufonyl chloride to obtain 4-methylthio-1-butylmethysulfonate; (c) reacting4-methylthio-1-butylmethysulfonate with sodium azide in the presence of a phase transfer catalyst to obtain 1-azido-4-methylthiobutane; (d) reacting 1-azido-4-methylthiobutane with triphenylphosphine, and then carrying out reaction with carbon disulfide under a room temperature condition to obtain 1-isothiocyano-4-methylthiobutane; and (e) oxidizing1-isothiocyano-4-methylthiobutane with m-CPBA under a low temperature condition to obtain sulforaphane. The method provided by the invention has the advantages of simple technological process, easy treatment and high total yield (75%), and can achieve effective large-scale production of sulforaphane.