156722-18-8

Basic information

• Product Name: (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol
• Synonyms: (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol;Rostafuroxin;PST2238;(3β,5β,14β)-21,23-Epoxy-24-Norchola-20,22-diene-3,14,17-triol;Rostafuroxin (PST-2238);(3beta,5beta,14beta)-21,23-Epoxy-24-norchola-20,22-diene-3,14,17-triol;Rostafuroxin PST2284;(3beta,5beta,14beta)-21,23-Epoxy-24-norchola-20,22-diene-3,14,17-triol Rostafuroxin (PST 2238)
• CAS NO: 156722-18-8
• Molecular Formula: C₂₃H₃₄O₄
• Molecular Weight: 374.51366
• Product Categories: Inhibitors
• Mol File: 156722-18-8.mol

Chemical Properties

• Boiling Point: 451.3°Cat760mmHg
• Flash Point: 226.7°C
• Appearance: /
• Density: 1.226g/cm³
• Vapor Pressure: 6.24E-09mmHg at 25°C
• Refractive Index: 1.59
• Storage Temp.: Sealed in dry,Store in freezer, under -20°C
• Solubility: insoluble in H2O; insoluble in EtOH; ≥12.05 mg/mL in DMSO
• PKA: 14.02±0.70(Predicted)
• CAS DataBase Reference: (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol(CAS DataBase Reference)
• NIST Chemistry Reference: (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol(156722-18-8)
• EPA Substance Registry System: (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol(156722-18-8)

Safety Data

• Hazardous Substances Data: 156722-18-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol is used as a receptor blocker for the treatment of hypertension. It potently inhibits the binding of endogenous ouabain to the Na+/K+ ATPase, blocking the ouabain-dependent increase in Na+/K+ ATPase activity. (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7, 8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol has shown promise in normalizing mRNA levels and Na+/K+ ATPase activity in cultured renal cells with upregulated or increased activity. Additionally, it has demonstrated efficacy in decreasing the development of hypertension in Milan-hypertensive rats at very low doses.
However, in a Phase II clinical study, (3S,5R,8R,9S,10S,13R,14S,17R)-17-(3-furyl)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,15,16-dodecahydro-1H-cyclopenta[a]phenanthrene-3,14,17-triol did not reduce blood pressure in human patients at doses of 0.05-5.0 mg/d, indicating that further research and development may be necessary to optimize its therapeutic potential in the treatment of hypertension.

in vitro

at molecular level, in the kidney, rostafuroxin antagonizes eo by triggering of the src-epidermal growth factor receptor (egfr)-dependent signaling pathway leading to renal na+-k+ pump, and erk tyrosine phosphorylation and activation. in the vasculature, it normalizes the increased myogenic tone caused by nanomolar ouabain [1].

in vivo

rostafuroxin reduces blood pressure without affecting heart rate, and restores the normal activity of the renal na+-k+-atpase in mhs rats when orally treated at doses from 1 to 100 μg/kg/day. similarly, nua rats have their blood pressure normalized by rostafuroxin [1].

IC 50

2 μm for na+-k+-atpase

references

[1] ferrari p, ferrandi m, valentini g, bianchi g. rostafuroxin: an ouabain antagonist that corrects renal and vascular na+-k+-atpase alterations in ouabain and adducin-dependent hypertension. am j physiol regul integr comp physiol. 2006 mar;290(3):r529-35.

InChI:InChI=1/C23H34O4/c1-20-8-5-17(24)13-15(20)3-4-19-18(20)6-9-21(2)22(25,10-11-23(19,21)26)16-7-12-27-14-16/h7,12,14-15,17-19,24-26H,3-6,8-11,13H2,1-2H3/t15-,17+,18+,19-,20+,21-,22+,23+/m1/s1

Synthetic route

17α-hydroxydigitoxigenin (26629-41-4) → (3S,5R,8R,9S,10S,13S,14S,17S)-17-((E)-3-Hydroxy-1-hydroxymethyl-propenyl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,14,17-triol + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8)

Conditions	Yield
With diisobutylaluminium hydride In tetrahydrofuran; hexane at -65℃; for 5h;	A 5% B 56%

17α-hydroxydigitoxigenin (26629-41-4) → (3S,5R,8R,9S,10S,13S,14S,17S)-17-(2,5-Dihydro-furan-3-yl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,14,17-triol + (3S,5R,8R,9S,10S,13S,14S,17S)-17-((E)-3-Hydroxy-1-hydroxymethyl-propenyl)-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthrene-3,14,17-triol + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8)

Conditions	Yield
With diisobutylaluminium hydride In tetrahydrofuran for 2h; Ambient temperature; Yield given. Yields of byproduct given;

17α-hydroxydigitoxigenin (26629-41-4) → 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8)

Conditions	Yield
With sulfuric acid; diisobutylaluminium hydride In tetrahydrofuran; dichloromethane; cyclohexane; ethyl acetate

1H-imidazole (288-32-4) + dimethyltertiary butyl silyl chloride + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 17β-(3-furyl)-17α-methoxy-5β-androstane-3β,14 β-diol (158066-42-3) + 3β-(dimethyl-tert-butylsilyloxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol

Conditions	Yield
In N-methyl-acetamide; ethyl acetate; cyclohexene

Bromoacetaldehyde diethyl acetal (2032-35-1) + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2,2-diethoxyethoxy)-17β-(furan-3-yl)-5β-androstane-14β,17α-diol + 3β-(2-hydroxyethoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158066-27-4)

Conditions	Yield
With NaH In tetrahydrofuran; water; mineral oil

allyl bromide (106-95-6) + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(3-aminopropoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158066-29-6) + 3β-(prop-2-enoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158067-99-3)

Conditions	Yield
With NaH In tetrahydrofuran; hexane; ethyl acetate; mineral oil

N-(2-chloroethyl)-pyrrolidine (5050-41-9) + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2-(1-pyrrolidinyl)ethoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158066-31-0)

Conditions	Yield
With NaH In tetrahydrofuran; methanol; dichloromethane; water; mineral oil

3β-(2-(1-pyrrolidinyl)ethoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158066-31-0) + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β,17α-Bis(2-(1-pyrrolidinyl)ethoxy)-17β-(furan-3-yl)-5β-androstan-14β-ol

3β,17α-dihydroxy-14β,15β-epoxy-5β-card-20(22)-enolide (158068-08-7) + 17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 14β,15β-epoxy-17β-(3-furyl)-5β-androstane-3β,17α-diol (158066-60-5)

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2,3-ditosyloxypropoxy)-17β-(furan-3-yl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 3 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: hexane; water; ethyl acetate; acetone; tert-butyl alcohol 3: pyridine; hexane; water; ethyl acetate View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2-methylaminoethoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 3 steps 1: NaH / tetrahydrofuran; water; mineral oil 2: pyridine; water; ethyl acetate 3: methylamine / methanol View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(3-hydroxypropoxy)-17β-(furan-3-yl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: sodium hydroxide; dihydrogen peroxide; potassium carbonate / tetrahydrofuran; ethanol; hexane; water; ethyl acetate View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(3-aminopropoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158066-29-6)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: sodium hydroxide; dihydrogen peroxide; potassium carbonate / tetrahydrofuran; ethanol; hexane; water; ethyl acetate 3: triphenylphosphine / tetrahydrofuran; hexane; ethyl acetate 4: hydrazine hydrate / methanol; ethanol; dichloromethane; water View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2,3-dihydroxypropoxy)-17β-(furan-3-yl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: hexane; water; ethyl acetate; acetone; tert-butyl alcohol View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2-(1-pyrrolidinyl)ethoxy)-17β-(3-furyl)-17α-methoxy-5β-androstan-14β-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; methanol; dichloromethane; water; mineral oil View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(3-guanidinopropoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: ethanol View Scheme
Multi-step reaction with 5 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: sodium hydroxide; dihydrogen peroxide; potassium carbonate / tetrahydrofuran; ethanol; hexane; water; ethyl acetate 3: triphenylphosphine / tetrahydrofuran; hexane; ethyl acetate 4: hydrazine hydrate / methanol; ethanol; dichloromethane; water 5: ethanol View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(2-(2-(1-pyrrolidinyl)ethoxy)ethoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; water; mineral oil 2: pyridine; water; ethyl acetate View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β,17α-bis(2-(1-pyrrolidinyl)ethoxy)-17β-(3-furl)-5β-androstan-14β-ol

Conditions	Yield
Multi-step reaction with 3 steps 1: NaH / tetrahydrofuran; methanol; dichloromethane; water; mineral oil View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β,17α-Bis(2-(1-pyrrolidinyl)ethoxy)-17β-(furan-3-yl)-5β-androstan-14β-ol

Conditions	Yield
Multi-step reaction with 2 steps 1: NaH / tetrahydrofuran; methanol; dichloromethane; water; mineral oil View Scheme

17-β-(3-furyl)-5-β-androstane-3-β, 14-β, 17-α-triol (156722-18-8) → 3β-(3-phthalimidopropoxy)-17β-(3-furyl)-5β-androstane-14β,17α-diol (158068-01-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: NaH / tetrahydrofuran; hexane; ethyl acetate; mineral oil 2: sodium hydroxide; dihydrogen peroxide; potassium carbonate / tetrahydrofuran; ethanol; hexane; water; ethyl acetate 3: triphenylphosphine / tetrahydrofuran; hexane; ethyl acetate View Scheme

Upstream product

• 26629-41-4 17α-hydroxydigitoxigenin 

Relevant articles and documents

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