95975-55-6

Usage

Uses

Used in Pharmaceutical Industry:
(Z)-Guggulsterone is used as a broad-spectrum steroid receptor ligand for its ability to modulate the activity of various steroid receptors, such as farnesoid X receptor (FXR) and pregnane X receptor (PXR). This makes it a potential therapeutic agent for treating a wide range of diseases, including metabolic disorders, inflammation, and cancer.
Used in Antihyperlipidemic Applications:
(Z)-Guggulsterone is used as an antihyperlipidemic drug for its ability to lower serum lipid levels, such as cholesterol and triglycerides. It is believed to exert its hypolipidemic effects through multiple mechanisms, including the activation of FXR, which regulates bile acid synthesis and metabolism, and the inhibition of HMG-CoA reductase, a key enzyme in cholesterol synthesis.
Used in Anti-inflammatory Applications:
(Z)-Guggulsterone is used as an anti-inflammatory agent for its ability to modulate the activity of various inflammatory pathways, such as the NF-κB and MAPK signaling pathways. This makes it a potential therapeutic agent for treating inflammatory diseases, such as arthritis, atherosclerosis, and inflammatory bowel disease.
Used in Anticancer Applications:
(Z)-Guggulsterone is used as an anticancer agent for its ability to inhibit the growth and proliferation of cancer cells, as well as to induce apoptosis. It has been shown to exert its anticancer effects through multiple mechanisms, including the modulation of steroid receptors, inhibition of cell cycle progression, and induction of oxidative stress.
Used in Drug Delivery Systems:
To enhance the bioavailability and therapeutic efficacy of (Z)-Guggulsterone, various drug delivery systems have been developed. These systems aim to improve the solubility, stability, and targeted delivery of (Z)-Guggulsterone, thereby enhancing its pharmacological activity and reducing potential side effects.

Biological Activity

Broad spectrum steroid receptor ligand; binds with high affinity to mineralocorticoid receptors (K i = 39 nM) and lower affinity to progesterone, androgen and glucocorticoid receptors (K i values are 201, 240 and 224 nM respectively). Functions primarily as an antagonist of these receptors, with the exception of the progesterone receptor where it displays partial agonist effects. Also exerts hypolipidemic activity, likely via antagonism of the receptor for bile acids (farnesoid X receptor; FXR).

InChI:InChI=1/C21H28O2/c1-4-16-19(23)12-18-15-6-5-13-11-14(22)7-9-20(13,2)17(15)8-10-21(16,18)3/h4,11,15,17-18H,5-10,12H2,1-3H3/b16-4+/t15-,17+,18+,20+,21-/m1/s1

Synthetic route

5,17(20)-dien-pregna-3,16-diol (672308-23-5) → pregna-4,17-diene-3,16-dione (95975-55-6)

Conditions	Yield
Stage #1: 5,17(20)-dien-pregna-3,16-diol With aluminum isopropoxide In cyclohexanone; toluene for 4h; Heating / reflux; Stage #2: With sulfuric acid In cyclohexane; water; toluene	50%

2-ethyl-2-methyl-1,3-dioxolane (126-39-6) + pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxypregna-5,17(20)-dien-16-one (115040-30-7, 115040-31-8)

Conditions	Yield
With toluene-4-sulfonic acid at 110℃; for 6h;	84%

pregna-4,17-diene-3,16-dione (95975-55-6) → 17α-hydroxy-16α-methylpregn-4-ene-3,20-dione (2868-02-2)

Conditions	Yield
Multi-step reaction with 9 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C 9: 100 percent / p-toluenesulfonic acid / acetone / 15 h / 25 - 30 °C View Scheme
Multi-step reaction with 9 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C 9: 100 percent / p-toluenesulfonic acid / acetone / 15 h / 25 - 30 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16α-methylpregn-5-ene-17α,20ξ-diol (115040-40-9)

Conditions	Yield
Multi-step reaction with 7 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating View Scheme
Multi-step reaction with 7 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16-methylpregna-5,16-dien-20-ol (115040-36-3, 115040-37-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-17,20-epoxy-16α-methylpregna-5-en-16-ol (115040-33-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 40 mg / Jones / acetone / 0.08 h / -15 °C View Scheme
Multi-step reaction with 3 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 40 mg / Jones / acetone / 0.08 h / -15 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16-methylpregna-5,16-dien-20-one (115040-38-5)

Conditions	Yield
Multi-step reaction with 5 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C View Scheme
Multi-step reaction with 5 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-17α-hydroxy-16α-methylpregn-5-en-20-one (115040-41-0)

Conditions	Yield
Multi-step reaction with 8 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C View Scheme
Multi-step reaction with 8 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16α,17α-epoxy-16β-methylpregn-5-en-20-one (115040-39-6)

Conditions	Yield
Multi-step reaction with 6 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C View Scheme
Multi-step reaction with 6 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 1-((8R,9S,10R,13S,14S,16R,17R)-17-Hydroxy-10,13,16-trimethyl-3-pyrrolidin-1-yl-2,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)-ethanone (96764-60-2)

Conditions	Yield
Multi-step reaction with 10 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C 9: 100 percent / p-toluenesulfonic acid / acetone / 15 h / 25 - 30 °C 10: 92 percent / propan-2-ol / 1 h / Heating View Scheme
Multi-step reaction with 10 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C 4: 5percent KOH / ethanol / 4 h / Heating 5: 197 mg / pyridinium chlorochromate / CH2Cl2 / 1 h / 30 °C 6: 96 percent / 30percent aq H2O2, 10percent aq NaOH / CH2Cl2; aq. ethanol / 48 h / 25 - 32 °C 7: 75 percent / LAH / tetrahydrofuran / 7 h / Heating 8: 0.95 g / 1) oxalyl chloride, DMSO, 2) triethylamine / CH2Cl2 / 2 h / -60 °C 9: 100 percent / p-toluenesulfonic acid / acetone / 15 h / 25 - 30 °C 10: 92 percent / propan-2-ol / 1 h / Heating View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16-methylpregna-5,16-diene-20-acetate (115040-34-1, 115040-35-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C View Scheme
Multi-step reaction with 3 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature 3: 80 percent / p-toluenesulfonic acid, acetic acid / CH2Cl2 / 0.33 h / -10 °C View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 3,3-ethylenedioxy-16α-methylpregna-5,17(20)-dien-16-ol (115059-20-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 40 percent / tetrahydrofuran / 24 h / Heating View Scheme
Multi-step reaction with 2 steps 1: 84 percent / p-toluenesulfonic acid / 6 h / 110 °C 2: 90 percent / TMEDA / diethyl ether / 3 h / Ambient temperature View Scheme

pregna-4,17-diene-3,16-dione (95975-55-6) → 4,17(20)-pregnadiene-3,16-diol (1283145-94-7)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 25℃; for 4.5h;	30.26 g

Upstream product

• 3347-58-8 5,17(20)-E-pregnadiene-3β,16α-diol 
• 39025-23-5 E-guggulsterone 
• 672308-23-5 5,17⁽²⁰⁾-dien-pregna-3,16-diol 

Downstream Products

• 39025-23-5 Z-guggulsterone 
• 2868-02-2 17α-hydroxy-16α-methylpregn-4-ene-3,20-dione 
• 61391-01-3 16β-hydroxy-4-pregnen-3-one 
• 61391-01-3 guggulsterol-VI 

Relevant academic research and scientific papers

Process for the synthesis of pharmacologically active (z/e)-guggulsterones

The invention relates to an improved process for producing pharmacologically active synthetic stereoisomeric mixture of guggulsterones (4) in the three steps. The mixture of gugguisterones consists of Z-guggulsterone [4,17(20)-trans-pregnadiene-3,16-dione] and E-guggulsterone [4,17(20)-cis-pregnadiene-3,16-dione] and could be in any relative ratio. This improved process comprises (a) epoxidation of 16-dehydropregnanolone acetate (1) with hydrogen peroxide (b) reduction of the so obtained epoxide (2) with hydrazine hydrate and (c) oxidation of the diol (3).

PROCESS FOR PREPARING GUGGULSTERONES AND GUGGULSTEROL

The present invention relates to a method for selective preparing 4,17 (20)-E-pregnadiene-3,16-dione (E-guggulsterone) of the formula (III) and 4,17 (20)-Z-pregnadiene-3,16-dione (Z-guggulsterone) of the formula (IV) having an effect of lowering the elevated low density lipoprotein (LDL) and high levels of the cholesterol effectively, and elevating the low levels of the high density lipoprotein (HDL) from a easy-available steroid of the following formula (I). Also, the present invention provides a method for preparation of the compound of the above formula (II).