522-17-8

Basic information

• Product Name: DEGUELIN
• Synonyms: (7as-cis)-oxy-;3h-bis(1)benzopyrano(3,4-b:6’,5’-e)pyran-7(7ah)-one,13,13a-dihydro-9,10-dimeth;(-)-DEGUELIN;DEGUELIN;(7AS,13AS)-13,13A-DIHYDRO-9,10-DIMETHOXY-3,3-DIMETHYL-3H-BIS[1]BENZOPYRANO[3,4-B:6',5'-E]PYRAN-7(7AH)-ONE;(7aS,13aS)-13,13a-Dihydro-9,10-dimethoxy-3,3-dimethyl-(3H)-bis[1]benzopyrano[3.4-b.6'.5'-e]pyran-7(7aH)-one;12a-DEOXYTEPHROSIN;(7aS)-3,3-Dimethyl-9,10-dimethoxy-7,7aα,13,13aα-tetrahydro-3H-bis[1]benzopyrano[3,4-b:6',5'-e]pyran-7-one
• CAS NO: 522-17-8
• Molecular Formula: C₂₃H₂₂O₆
• Molecular Weight: 394.42
• EINECS: 200-258-5
• Product Categories: Miscellaneous Natural Products;Antitumour
• Mol File: 522-17-8.mol

Chemical Properties

• Melting Point: 85-87 °C(lit.)
• Boiling Point: 560.127 °C at 760 mmHg
• Flash Point: 244.739 °C
• Appearance: white to yellow/solid
• Density: 1.255 g/cm³
• Vapor Pressure: 1.41E-12mmHg at 25°C
• Refractive Index: 1.583
• Storage Temp.: −20°C
• Solubility: DMSO: >10 mg/mL
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 3 months.
• CAS DataBase Reference: DEGUELIN(CAS DataBase Reference)
• NIST Chemistry Reference: DEGUELIN(522-17-8)
• EPA Substance Registry System: DEGUELIN(522-17-8)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: DX1500000
• Hazardous Substances Data: 522-17-8(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
Deguelin is used as an antineoplastic agent for its chemopreventive and chemosensitizing effects in models of skin, mammary, colon, and lung carcinogenesis. It inhibits cell growth, blocks PI3K/Akt activation, suppresses COX-2 expression, and induces apoptosis in premalignant and squamous human bronchial epithelial (HBE) cells without affecting normal HBE cells.
Used in Antiviral Applications:
Deguelin is used as an antiviral compound to study its inhibitory effects on human cytomegalovirus (HCMV)-infected human foreskin fibroblast (HFF) cells.
Used in Insecticide Applications:
Originally isolated to be used as an insecticide and fish poison, deguelin is employed in the agricultural industry for pest control.
Used in Drug Delivery Systems:
Deguelin is used as a nicotinamide adenine dinucleotide hydrogen (NADH) dehydrogenase (Complex I) inhibitor to study its effects on mitochondrial respiratory inhibition in human hepatocarcinoma cells (HepG2) and human renal proximal tubule epithelial cells (RPTECs).
Used in Analytical Chemistry:
Deguelin serves as an analytical standard in high-performance liquid chromatography (HPLC) for accurate and precise measurements in various chemical analyses.
Used in Parkinson's Disease Research:
At 6 mg/kg, deguelin induces Parkinson’s disease-like symptoms in rats after six days of subcutaneous infusion, making it a useful model for Parkinson’s disease research.

Biological Activity

Anticancer and antiviral agent; chemopreventive and pro-apoptotic. Inhibits phorbol ester-induced ornithine decarboxylase and NADH:ubiquinone oxidoreductase activities (IC 50 values are 11 and 6.9 nM respectively). Inhibits PI 3-kinase and reduces pAkt levels in pre-malignant and malignant human bronchial epithelial cells. Active in vivo .

Biochem/physiol Actions

Deguelin is a natural rotenoid compound present abundantly in barks, leaves, seeds, and roots of the plants belonging to the Leguminosae family. Deguelin has been studied as a therapeutic agent against the skin, lung cancer, and mammary tumorigenesis.

References

1) Chun et al. (2003), Effects of deguelin on the phosphatidylinositol 3- kinase/Akt pathway and apoptosis in premalignant human bronchial epithelial cells; J. Natl. Cancer Inst., 95 291 2) Kang et al. (2012), Deguelin, an AKT Inhibitor, Down-Regulates NFκB Signaling and Induces Apoptosis in Colon Cancer Cells and Inhibits Tumor Growth in Mice; Dig. Dis. Sci.,?57 2873 3) Lee et al. (2004), Molecular mechanisms of deguelin-induced apoptosis in transformed human bronchial epithelial cells; Biochem. Pharmacol., 68 1119 4) Ito et al. (2004), Cancer chemopreventive activity of rotenoids from Derris trifoliata; Planta Med., 70 8

InChI:InChI=1/C23H22O6/c1-23(2)8-7-12-15(29-23)6-5-13-21(24)20-14-9-17(25-3)18(26-4)10-16(14)27-11-19(20)28-22(12)13/h5-10,19-20H,11H2,1-4H3/t19-,20+/m1/s1

Upstream product

• 186581-53-3 diazomethane 
• 147807-70-3 (7aS,13aS)-10-hydroxy-13,13a-dihydro-9-methoxy-3,3-dimethyl-3H-chromeno[3,4-b]pyrano[2,3-h]chromen-7(7aH)-one 
• 522-17-8 (-)-deguelin 
• 70191-71-8 rotenonic acid 
• 3466-23-7 7a,13a-dehydrodeguelin 
• 2033-89-8 3,4-dimethoxyphenol 
• 79571-17-8 5-(methoxy)-2,2-dimethyl-2H-chromene-6-carbaldehyde 
• 616207-45-5 4-(3,4-dimethoxy-phenoxy)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-but-2-yn-1-one 
• 139006-28-3 amorphispironone 
• 124571-94-4 (6aS,12S,12aR)-2,3-Dimethoxy-8-(3-methyl-but-2-enyl)-6,6a,12,12a-tetrahydro-chromeno[3,4-b]chromene-9,12-diol 
• 124571-93-3 (6aS,12S,12aS,5'S)-12-deoxo-12-hydroxy-5'-phenylthio-4',5'-dihydrodeguelin 
• 76-80-2 tephrosin 
• 83-79-4 rotenone 
• 58277-58-0 (6aS,12aS,5’R)-rotenone hydrobromide 

Downstream Products

• 522-17-8 cis-deguelin 
• 124571-92-2 (1S,2R,7aS,13aS)-1-Chloro-9,10-dimethoxy-3,3-dimethyl-2-phenylsulfanyl-2,3,13,13a-tetrahydro-1H,7aH-pyrano[2,3-c;6,5-f']dichromen-7-one 
• 522-17-8 (+/-)-trans-deguelin 
• 1386350-03-3 (7S,7aR,3aS)-7-benzyloxy-9,10-dimethoxy-3,3-dimethyl-7,7a,13,13a-tetrahydro-3H-chromeno[3,4-b]pyrano[2,3-h]chromene 
• 1386350-15-7 (7aR,13aS)-9,10-dimethoxy-3,3-dimethyl-13,13a-dihydro-3H-chromeno[3,4-b]pyrano[2,3-h]chro men-7(7aH)-one O-benzyloxime 
• 76-80-2 tephrosin 
• 76-80-2 (+/-)-tephrosin 
• 207597-97-5 12aα-hydroxydeguelin 
• 76-80-2 (±)-12a-epi-tephrosin 

Relevant articles and documents

General Synthetic Approach to Rotenoids via Stereospecific, Group-Selective 1,2-Rearrangement and Dual S N Ar Cyclizations of Aryl Fluorides

A general synthetic approach to rotenoids is described, featuring 1) stereospecific, group-selective 1,2-rearrangements of epoxy alcohols, and 2) S N Ar oxy-cyclizations of aryl fluorides. The common intermediate epoxyketone, en route to (-)-rotenone and (-)-deguelin, was prepared from d -araboascorbic acid in five steps. Also described is the conversion of (-)-deguelin into oxidized congeners, (-)-tephrosin and (+)-12a- epi -tephrosin.

Concise Total Synthesis of (±)-Deguelin and (±)-Tephrosin Using a Vinyl Iodide as a Key Building Block

A concise and protecting-group-free total synthesis of the antiproliferative natural product (±)-deguelin (2) was accomplished in four steps and 62% overall yield from commercially available precursors. The key transformation employed a vinyl iodide as the pivotal building block to construct the 4-acylchromene substructure present in deguelin. Subsequent Cu2O-mediated α-hydroxylation of deguelin (2) afforded tephrosin (3) in 90% yield.

Stereocontrolled semi-syntheses of deguelin and tephrosin

We describe stereocontrolled semi-syntheses of deguelin and tephrosin, anti-cancer rotenoids isolated from Tephrosia vogelii. Firstly, we present a new two-step transformation of rotenone into rot-2′-enonic acid via a zinc-mediated ring opening of rotenone hydrobromide. Secondly, following conversion of rot-2′-enonic acid into deguelin, a chromium-mediated hydroxylation provides tephrosin as a single diastereoisomer. An étard-like reaction mechanism is proposed to account for the stereochemical outcome. Our syntheses of deguelin and tephrosin are operationally simple, scalable and high yielding, offering considerable advantages over previous methods.

NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a novel compound inhibiting Hsp 90 and to a pharmaceutical composition including same as an active ingredient. Compounds of formula 1 and formula 2 according to the present invention inhibit the accumulation of HIF-1α protein, which is an Hsp90 client protein, by suppressing Hsp90 expression, and effectively inhibit the activity of vascular endothelial growth factor (VEGF). Furthermore, said compounds have low cytotoxicity and can thus be used as an active ingredient for the treatment of diabetic retinopathy and arthritis.

NOVEL COMPOUND OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF, AND PHARMACEUTICAL COMPOSITION CONTAINING SAME AS ACTIVE INGREDIENT

The present invention relates to a compound inhibiting Hsp90 and a pharmaceutical composition comprising the same as an active ingredient. The compounds represented by formula 1 and formula 2 of the present invention suppress the expression of Hsp90 so that they can inhibit the accumulation of HIF-1α, the Hsp90 client protein, and also efficiently inhibit the activation of VEGF. In addition, these compounds display low cytotoxicity, so that they can be effectively used as an active ingredient of an anti-cancer agent, a diabetic retinopathy treating agent, and an anti-arthritic agent.

Total synthesis of (-)-deguelin via an iterative pyran-ring formation strategy

Enantioselective synthesis of (-)-deguelin was accomplished via an iterative pyran-ring formation approach. The key features involve the anionic addition of a chromene unit to aryloxy alkyl aldehyde for the double cyclization precursor and iterative pyran ring formation by Pd-catalyzed O-arylation and C-arylation, respectively. This journal is

A concise enantioselective synthesis and cytotoxic evaluation of the anticancer rotenoid deguelin enabled by a tandem Knoevenagel/conjugate addition/decarboxylation sequence

(-)-Deguelin is a rotenoid natural product that possesses significant potential as a chemopreventive and chemotherapeutic agent. While several racemic syntheses of deguelin have been reported, a formal evaluation of the anticancer activity of both the natural and unnatural enantiomers remains lacking. We describe herein the successful application of a flexible and selective thiourea-catalyzed cyclization strategy toward the enantioselective total synthesis of deguelin, which allows access to either stereoisomer for biological studies. The synthesis was completed in six steps (longest linear) with no protecting groups. The evaluation of both enantiomers of the natural product demonstrated potent inhibition of several cancer cell lines by these compounds, but interestingly showed that the unnatural (+)-deguelin preferentially inhibited the growth of MCF-7 breast cancer and HepG2 liver carcinoma cells when compared to the natural product.

Design, synthesis, and biological evaluation of novel deguelin-based heat shock protein 90 (HSP90) inhibitors targeting proliferation and angiogenesis

Deguelin exhibits potent apoptotic and antiangiogenic activities in a variety of transformed cells and cancer cells. Deguelin also exhibits potent tumor suppressive effects in xenograft tumor models for many human cancers. Our initial studies confirmed that deguelin disrupts ATP binding to HSP90 and consequently induces destabilization of its client proteins such as HIF-1α. Interestingly, a fluorescence probe assay revealed that deguelin and its analogues do not compete with ATP binding to the N-terminus of HSP90, unlike most HSP90 inhibitors. To determine the key parts of deguelin that contribute to its potent HSP90 inhibition, as well as its antiproliferative and antiangiogenic activities, we have established a structure-activity relationship (SAR) of deguelin. In the course of these studies, we identified a series of novel and potent HSP90 inhibitors. In particular, analogues 54 and 69, the B- and C-ring-truncated compounds, exhibited excellent antiproliferative activities with IC50 of 140 and 490 nM in the H1299 cell line, respectively, and antiangiogenic activities in zebrafish embryos in a dose dependent manner (0.25-1.25 μM).

Concise modular asymmetric synthesis of deguelin, tephrosin and investigation into their mode of action

(Figure Presented) The concise nature and modularity of the synthesis described for deguelin and tephrosin (retrosynthetic analysis depicted) should facilitate access to labeled analogues to dissect the mechanism of action of this important pharmacophore.

Contrast agents for myocardial perfusion imaging

The present disclosure is directed, in part, to compounds and methods for imaging myocardial perfusion, comprising administering to a patient a contrast agent which comprises a compound that binds MC-1, and an imaging moiety, and scanning the patient using diagnostic imaging.