38462-04-3

Basic information

• Product Name: ascofuranone
• Synonyms: ascofuranone;2-Methyl-3-chloro-4,6-dihydroxy-5-[(2E,6E)-3-methyl-7-[(2S)-4-oxo-5,5-dimethyltetrahydrofuran-2-yl]-2,6-octadienyl]benzaldehyde;3-Chloro-4,6-dihydroxy-2-methyl-5-[(2E,6E)-3-methyl-7-[(S)-tetrahydro-5,5-dimethyl-4-oxofuran-2-yl]-2,6-octadienyl]benzaldehyde;Ascofranone;Ascofuranon
• CAS NO: 38462-04-3
• Molecular Formula: C₂₃H₂₉ClO₅
• Molecular Weight: 420.93
• Mol File: 38462-04-3.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 581.2°C at 760 mmHg
• Flash Point: 305.3°C
• Appearance: /
• Density: 1.207g/cm³
• Vapor Pressure: 4.18E-14mmHg at 25°C
• Refractive Index: 1.577
• CAS DataBase Reference: ascofuranone(CAS DataBase Reference)
• NIST Chemistry Reference: ascofuranone(38462-04-3)
• EPA Substance Registry System: ascofuranone(38462-04-3)

Safety Data

• Hazardous Substances Data: 38462-04-3(Hazardous Substances Data)

Usage

Description

(-)-Ascofuranone is a naturally occurring compound with antibiotic and antitumor properties. It is known for its ability to suppress gene activation related to matrix metalloproteinase-9 and has demonstrated effectiveness in treating Trypanosoma brucei brucei infection in mice.

Uses

Used in Pharmaceutical Applications:
(-)-Ascofuranone is used as an antibiotic for its antitumor activity, targeting and suppressing PMA-mediated matrix metalloproteinase-9 gene activation through the Ras/Raf/MEK/ERKand Ap1-dependent mechanisms. This makes it a potential candidate for the development of new cancer treatments.
Used in Infectious Disease Treatment:
In the field of infectious diseases, (-)-Ascofuranone is used as a therapeutic agent for treating Trypanosoma brucei brucei infection in mice, showcasing its potential in combating parasitic infections.

Safety Profile

Moderately toxic byintraperitoneal route. Whenheated to decomposition it emits toxic fumes of Cl-.

InChI:InChI=1/C23H29ClO5/c1-13(7-6-8-14(2)18-11-19(26)23(4,5)29-18)9-10-16-21(27)17(12-25)15(3)20(24)22(16)28/h8-9,12,18,27-28H,6-7,10-11H2,1-5H3/b13-9+,14-8+/t18-/m0/s1

Synthetic route

(1''S,4''S)-(-)-ascofuranol (51759-79-6) → Ascofuranone (38462-04-3)

Conditions	Yield
With pyridinium chlorochromate In dichloromethane for 3h; Ambient temperature;	22.2%

(2E,6E,1'S,4'S)-(+)-7-(4'-hydroxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate (99529-56-3) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 9 steps 1: imidazole / dimethylformamide / 6 h / Ambient temperature 2: 92.9 percent / K2CO3 / methanol; H2O / 48 h / Ambient temperature 3: 1.26 g / n-BuLi, Ph3CH, p-TsCl, LiCl / diethyl ether; hexamethylphosphoric acid triamide; hexane / 0.42 h / 0 °C 4: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 5: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 6: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 7: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 8: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 9: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2E,6E,1'S*,4'S*)-7-(4'-hydroxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate (99477-55-1, 99529-54-1, 99529-56-3, 99529-57-4) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 11 steps 1: 5.14 g / 14 h / 80 °C 2: 76.3 percent / Et3N, HSiCl3 / benzene / 96 h / Ambient temperature 3: imidazole / dimethylformamide / 6 h / Ambient temperature 4: 92.9 percent / K2CO3 / methanol; H2O / 48 h / Ambient temperature 5: 1.26 g / n-BuLi, Ph3CH, p-TsCl, LiCl / diethyl ether; hexamethylphosphoric acid triamide; hexane / 0.42 h / 0 °C 6: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 7: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 8: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 9: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 10: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 11: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2E,6E,1'S,4'S)-(+)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadien-1-ol (99477-58-4) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 7 steps 1: 1.26 g / n-BuLi, Ph3CH, p-TsCl, LiCl / diethyl ether; hexamethylphosphoric acid triamide; hexane / 0.42 h / 0 °C 2: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 3: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 4: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 5: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 6: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 7: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2E,6E,1'S,4'S)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl chloride (99477-59-5) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 6 steps 1: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 2: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 3: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 4: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 5: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 6: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2E,6E,1'S,4'S)-(+)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate (99477-57-3, 99529-58-5) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 8 steps 1: 92.9 percent / K2CO3 / methanol; H2O / 48 h / Ambient temperature 2: 1.26 g / n-BuLi, Ph3CH, p-TsCl, LiCl / diethyl ether; hexamethylphosphoric acid triamide; hexane / 0.42 h / 0 °C 3: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 4: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 5: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 6: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 7: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 8: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2'E,6'E,1''S,4''S)-(+)-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>-2,4-dimethoxy-6-methyl-1,4-cyclohexadiene (99477-60-8) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 5 steps 1: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 2: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 3: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 4: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 5: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2'E,6'E,1''S,4''S)-4-chloro-2-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>orcinol (99477-62-0) → Ascofuranone (38462-04-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 2: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 3: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2'E,6'E,1''S,4''S)-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>-1,5-dichloro-6-methyl-2,4-cyclohexanedione (99477-61-9) → Ascofuranone (38462-04-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 2: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 3: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 4: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

(2'E,6'E,1''S,4''S)-5-chloro-2,4-dihydroxy-6-methyl-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>benzaldehyde (99477-63-1) → Ascofuranone (38462-04-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 2: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

Acetic acid (2E,6E)-7-[(2S,4S)-5,5-dimethyl-4-((R)-1-naphthalen-1-yl-ethylcarbamoyloxy)-tetrahydro-furan-2-yl]-3-methyl-octa-2,6-dienyl ester (99477-56-2) → Ascofuranone (38462-04-3)

Conditions

Yield

Multi-step reaction with 10 steps 1: 76.3 percent / Et3N, HSiCl3 / benzene / 96 h / Ambient temperature 2: imidazole / dimethylformamide / 6 h / Ambient temperature 3: 92.9 percent / K2CO3 / methanol; H2O / 48 h / Ambient temperature 4: 1.26 g / n-BuLi, Ph3CH, p-TsCl, LiCl / diethyl ether; hexamethylphosphoric acid triamide; hexane / 0.42 h / 0 °C 5: n-BuLi, HMPA / tetrahydrofuran; hexane / 0.75 h / -70 °C 6: 50.2 percent / CaCO3, NCS / H2O; dimethylformamide / Ambient temperature 7: 57 percent / DBU / tetrahydrofuran / 6 h / Heating 8: 1) EtMgBr / 1) ether, room temp., 1 h. 10 min.; 2) ether evaporated; 100 degC, 10 min. 9: 71 percent / HF / acetonitrile; H2O / 1 h / Ambient temperature 10: 22.2 percent / pyridinium chlorochromate / CH2Cl2 / 3 h / Ambient temperature View Scheme

acetic anhydride (108-24-7) + Ascofuranone (38462-04-3) → 2,4-O-di-acetylascofuranone

Conditions	Yield
With pyridine at 20℃; Product distribution / selectivity;	100%

Ascofuranone (38462-04-3) + dimethyl sulfate (77-78-1) → 4-O-Methyl-ascofuranone

Conditions	Yield
With potassium carbonate In acetone for 1h; Heating / reflux;	93%

ethyl bromoacetate (105-36-2) + Ascofuranone (38462-04-3) → ethyl {2-chloro-6-[(2E,6E)-7-((S)-2,2-dimethyl-3-oxotetrahydrofuran-5-yl)-3-methyl-2,6-octadienyl]-4-formyl-5-hydroxy-3-methylphenoxy}acetate

Conditions	Yield
Stage #1: Ascofuranone With sodium hydride In N,N-dimethyl-formamide at 20℃; for 0.166667h; Stage #2: ethyl bromoacetate In N,N-dimethyl-formamide at 40℃; for 5.5h;	88%

Ascofuranone (38462-04-3) + methyl iodide (74-88-4) → 4-O-Methyl-ascofuranone

Conditions	Yield
With potassium carbonate In acetone for 1h; Heating;	87%

acetic anhydride (108-24-7) + Ascofuranone (38462-04-3) → 4-O-Acetyl-ascofuranone (60217-09-6)

Conditions	Yield
With pyridine at 20℃;	68%

pyridine-3-carbonyl chloride hydrochloride (20260-53-1) + Ascofuranone (38462-04-3) → 4-O-Nicotinoyl-ascofuranone

Conditions	Yield
With pyridine at 20℃;	67%

isonicotinoyl chloride hydrochloride (39178-35-3) + Ascofuranone (38462-04-3) → 4-O-Isonicotinoyl-ascofuranone

Conditions	Yield
In pyridine at 20℃; for 1h;	54%
Stage #1: isonicotinoyl chloride hydrochloride; Ascofuranone With pyridine at 20℃; for 1h; Stage #2: With water at 20℃; for 0.5h;	54%

glutaric anhydride, (108-55-4) + Ascofuranone (38462-04-3) → 4-O-(4-Carboxybutanoyl)ascofuranone

Conditions	Yield
With pyridine; dmap at 50℃;	32%

Ascofuranone (38462-04-3) → 3-chloro-4,6-dihydroxy-2-methyl-5-[3-methyl-7-(tetrahydro-5,5-dimethyl-4-oxo-2-furanyl)octyl]-benzaldehyde (1027952-60-8)

Conditions	Yield
With hydrogen; 5%-palladium/activated carbon In ethanol at 0℃; for 3h;	25%

Ascofuranone (38462-04-3) → Dehydroascofuranone

Conditions	Yield
With sodium hydroxide; silver nitrate In 1,4-dioxane at 20℃; for 3h;	24%
With sodium hydroxide; silver nitrate In 1,4-dioxane; water at 20℃; for 3h;	24%

Ascofuranone (38462-04-3) → 5-[(E,E)-7-(3-chloro-2,6-dihydroxy-5-hydroxyiminomethyl-4-methylphenyl)-1,5-dimethyl-1,5-heptadienyl]-4,5-dihydro-2,2-dimethyl-3(2H)-furanone

Conditions	Yield
With pyridine; hydroxylamine hydrochloride at 20 - 25℃; for 3.5h;	20%

Ascofuranone (38462-04-3) → 2-O-Methyl-ascofuranone

Conditions	Yield
Multi-step reaction with 3 steps 1: 68 percent / pyridine / 20 °C 2: 24 percent / K2CO3 / acetone / 2 h / Heating 3: 90 percent / aq. NaOH / methanol / 4 h / 20 °C View Scheme

Ascofuranone (38462-04-3) → 4-O-Acetyl-2-O-methyl-ascofuranone (290361-56-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: 68 percent / pyridine / 20 °C 2: 24 percent / K2CO3 / acetone / 2 h / Heating View Scheme

Ascofuranone (38462-04-3) → 4-O-Carboxymethyl-ascofuranone

Conditions	Yield
Multi-step reaction with 2 steps 1.1: NaH / dimethylformamide / 0.17 h / 20 °C 1.2: 88 percent / dimethylformamide / 5.5 h / 40 °C 2.1: 91 percent / aq. K2CO3 / methanol / 2 h / 20 °C View Scheme

Upstream product

• 51759-79-6 (1''S,4''S)-(-)-ascofuranol 
• 99529-56-3 (2E,6E,1'S,4'S)-(+)-7-(4'-hydroxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate 
• 99477-55-1 (2E,6E,1'S*,4'S*)-7-(4'-hydroxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate 
• 99477-58-4 (2E,6E,1'S,4'S)-(+)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadien-1-ol 
• 99477-59-5 (2E,6E,1'S,4'S)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl chloride 
• 99477-57-3 (2E,6E,1'S,4'S)-(+)-7-(4'-t-butyldimethylsilyloxy-3',3'-dimethyl-2'-oxacyclopentyl)-3,7-dimethyl-2,6-heptadienyl acetate 
• 99477-60-8 (2'E,6'E,1''S,4''S)-(+)-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>-2,4-dimethoxy-6-methyl-1,4-cyclohexadiene 
• 99477-62-0 (2'E,6'E,1''S,4''S)-4-chloro-2-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>orcinol 
• 99477-61-9 (2'E,6'E,1''S,4''S)-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>-1,5-dichloro-6-methyl-2,4-cyclohexanedione 
• 99477-63-1 (2'E,6'E,1''S,4''S)-5-chloro-2,4-dihydroxy-6-methyl-3-<7'-(4''-t-butyldimethylsilyloxy-3'',3''-dimethyl-2''-oxacyclopentyl)-3',7'-dimethyl-2',6'-heptadienyl>benzaldehyde 
• 99477-56-2 Acetic acid (2E,6E)-7-[(2S,4S)-5,5-dimethyl-4-((R)-1-naphthalen-1-yl-ethylcarbamoyloxy)-tetrahydro-furan-2-yl]-3-methyl-octa-2,6-dienyl ester 

Downstream Products

• 1027952-60-8 3-chloro-4,6-dihydroxy-2-methyl-5-[3-methyl-7-(tetrahydro-5,5-dimethyl-4-oxo-2-furanyl)octyl]-benzaldehyde 
• 290361-56-7 4-O-Acetyl-2-O-methyl-ascofuranone 
• 60217-09-6 4-O-Acetyl-ascofuranone 

Relevant articles and documents

SYNTHESIS OF THE NATURAL ENANTIOMERS OF ASCOCHLORIN, ASCOFURANONE AND ASCOFURANOL

Three fungal metabolites with a common structural feature as prenylated phenols were synthesized in their naturally occuring and optically active forms: ascochlorin benzaldehyde>, ascofuranone and ascofuranol benzaldehyde>. (+)-Ascofuranone and (+)-ascofuranol were also synthesized.By the present synthesis the absolute configuration of the natural (-)-ascofuranol was established as (1''S,4''S).