1343403-10-0

Basic information

• Product Name: (3R,3As,3Bs,6As,8As,9Ar)-Octahydro-3-Hydroxy-3,8A-DiMethyl-6-Methylene-1H-Oxireno[8,8A]Azuleno[4,5-B]Furan-5(6H)-One
• Synonyms: (3R,3As,3Bs,6As,8As,9Ar)-Octahydro-3-Hydroxy-3,8A-DiMethyl-6-Methylene-1H-Oxireno[8,8A]Azuleno[4,5-B]Furan-5(6H)-One;Epoxymicheliolide;1b,10b-Epoxymicheliolide;Epoxy costus lactone
• CAS NO: 1343403-10-0
• Molecular Formula: C₁₅H₂₀O₄
• Molecular Weight: 264.32
• Mol File: 1343403-10-0.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 451.6±45.0 °C(Predicted)
• Appearance: /
• Density: 1.28±0.1 g/cm3(Predicted)
• PKA: 14.65±0.40(Predicted)
• CAS DataBase Reference: (3R,3As,3Bs,6As,8As,9Ar)-Octahydro-3-Hydroxy-3,8A-DiMethyl-6-Methylene-1H-Oxireno[8,8A]Azuleno[4,5-B]Furan-5(6H)-One(CAS DataBase Reference)
• NIST Chemistry Reference: (3R,3As,3Bs,6As,8As,9Ar)-Octahydro-3-Hydroxy-3,8A-DiMethyl-6-Methylene-1H-Oxireno[8,8A]Azuleno[4,5-B]Furan-5(6H)-One(1343403-10-0)
• EPA Substance Registry System: (3R,3As,3Bs,6As,8As,9Ar)-Octahydro-3-Hydroxy-3,8A-DiMethyl-6-Methylene-1H-Oxireno[8,8A]Azuleno[4,5-B]Furan-5(6H)-One(1343403-10-0)

Safety Data

• Hazardous Substances Data: 1343403-10-0(Hazardous Substances Data)

Usage

Uses

(1aS,3aS,6aS,6bS,7R,9aR)-7-Hydroxy-1a,7-dimethyl-4-methyleneoctahydro-1aH-oxireno[2'',3'':8,8a]azuleno[4,5-b]furan-5(6aH)-one is a reactant in the sysnthesis of Arglabin (A769750), a sesquiterpene lactone used in the inhibition of glucose induced NF-kB activation and MCP-1/TGF-β1 expression treating diabetic nephropathy. Cytocoxic.

Synthetic route

micheliolide → (1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0)

Conditions	Yield
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; for 6h;	91%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 20℃; Solvent; Reagent/catalyst; Temperature;	85%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane	75%

micheliolide → (1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) + (3aS,5S,9R,9aS,9bS)-5,9-dihydroxy-6,9-dimethyl-3-methylene-3a,4,5,7,8,9,9a,9b-octahydroazuleno[4,5-b]furan-2(3H)-one + (3aS,6R,9R,9aS,9bS)-6,9-dihydroxy-6,9-dimethyl-3-methylene-3a,4,5,6,8,9,9a,9b-octahydroazuleno[4,5-b]furan-2(3H)-one

Conditions	Yield
With tert.-butylhydroperoxide; selenium(IV) oxide In dichloromethane; water for 3h;	A 14% B 53% C 7%

parthenolide (503551-53-9) → (1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 23 h / 20 °C / Large scale reaction 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 20 °C 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 20 °C View Scheme

5β-epoxy-germacra-1-(10),11-(13)-dien-12,6α-olide → (1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane 2: 3-chloro-benzenecarboperoxoic acid / dichloromethane View Scheme

parthenolide (503551-53-9) → (1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) + (3aS,5S,9R,9aS,9bS)-5,9-dihydroxy-6,9-dimethyl-3-methylene-3a,4,5,7,8,9,9a,9b-octahydroazuleno[4,5-b]furan-2(3H)-one + (3aS,6R,9R,9aS,9bS)-6,9-dihydroxy-6,9-dimethyl-3-methylene-3a,4,5,6,8,9,9a,9b-octahydroazuleno[4,5-b]furan-2(3H)-one

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / dichloromethane / 20 °C 2: selenium(IV) oxide; tert.-butylhydroperoxide / water; dichloromethane / 3 h View Scheme

(1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) + dimethyl amine (124-40-3) → C17H27NO4

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water at 20℃;	96%

(1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) + d6-dimethylamine hydrochloride (53170-19-7) → C17H21(2)H6NO4

Conditions	Yield
With potassium carbonate In tetrahydrofuran at 20℃;	90%

(1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) → 1β,10β-Epoxyguaia-3,11(13)-dien-12,6α-olide (137624-14-7, 84692-91-1)

Conditions	Yield
With Martins sulfurane In dichloromethane at 20℃; for 24h; Inert atmosphere;	67%
With Martins sulfurane In dichloromethane for 24h; Solvent; Reagent/catalyst; Inert atmosphere;	65%
With pyridine; trichlorophosphate at 0℃; for 2h;	45%

(1R,3aR,4aS,6aS,9aS,9bS)-1-hydroxy-1,4a-dimethyl-7-methyleneoctahydro-1H-oxireno[2',3':8,8a]azuleno[4,5-b]furan-8(4aH)-one (1343403-10-0) → C17H19(2)H6NO3

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine; trichlorophosphate / 2 h / 0 °C 2: potassium carbonate / tetrahydrofuran / 20 °C View Scheme

Upstream product

• 503551-53-9 parthenolide 
• 68370-47-8 (3aS,9R,9aS,9bS)-9-hydroxy-6,9-dimethyl-3-methylene-3a,4,5,7,8,9,9a,9b-octahydroazuleno[4,5-b]furan-2(3H)-one 

Downstream Products

• 137624-14-7 1β,10β-Epoxyguaia-3,11(13)-dien-12,6α-olide 

Relevant articles and documents

Design, synthesis and in vivo anticancer activity of novel parthenolide and micheliolide derivatives as NF-κB and STAT3 inhibitors

Parthenolide and micheliolide have attracted great attention in anticancer research due to their unique activities. In this study, thirteen parthenolide derivatives and twenty-three micheliolide derivatives were synthesized. Most synthesized compounds showed higher cytotoxicity than parthenolide or micheliolide. The in vivo anticancer activity of several representative compounds was evaluated in mice. One micheliolide derivative, 9-oxomicheliolide (43), showed promising in vivo antitumor activity compared with clinical drugs cyclophosphamide or temozolomide. Compound 43 was particularly effective against glioblastoma, with its tumor inhibition rate in mice comparable to the drug temozolomide. The discovery of compound 43 also demonstrates the feasibility of developing anticancer micheliolide derivatives by modification at C-9 position. Anticancer mechanism studies revealed that 9-oxomicheliolide exhibited inhibition effect against NF-κB and STAT3 signaling pathways, as well as induction effects of cell apoptosis. It is postulated that 9-oxomicheliolide is likely to be a modulator of the immune system, which regulates the anticancer immune responses.

Process for the preparation of Arglabin

The present invention relates to the preparation method of arglabin, comprising reacting micheliolide with epoxidation reagent to obtain 1,10-epoxy micheliolide and dehydration of 4-hydroxy and 3-hydrogen of 1,10-epoxy micheliolide to obtain arglabin. The character of the method is that arglabin is prepared from micheliolide through the crucial intermediate of 1,10-epoxy micheliolide.

USES OF SESQUITERPENE LACTONE COMPOUNDS AND THEIR DERIVATIVES IN DRUGS PREPARATION

The present invention relates to the uses of sesquiterpene lactone compounds and their derivatives in preparing drugs. It belongs to the field of drug technology, specifically relates to the uses of the compounds of Formula (I) in preparing the drugs, especially the uses in preparing the drugs to treat rheumatoid arthritis and treat cancers through inhibiting cancer stem cells.