(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

Base Information

• Chemical Name: (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol
• CAS No.: 112965-21-6
• Molecular Formula: C27H40O3
• Molecular Weight: 412.613
• Hs Code.: 2906195000
• European Community (EC) Number: 601-218-4
• Wikipedia: Calcipotriol
• Mol file: 112965-21-6.mol

Synonyms:112965-21-6;SCHEMBL9360339;AKOS005146500;AC-4696;(1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

Chemical Property of (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

Chemical Property:

• Appearance/Colour: white crystalline solid
• Vapor Pressure: 5.74E-16mmHg at 25°C
• Melting Point: 166-168 ºC
• Refractive Index: 1.579
• Boiling Point: 582 ºC at 760 mmHg
• PKA: 14.29±0.20(Predicted)
• Flash Point: 250.6 ºC
• PSA: 60.69000
• Density: 1.12 g/cm³
• LogP: 5.09060
• Storage Temp.: Desiccate at -20°C
• Solubility.: DMSO: soluble15mg/mL, clear
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 412.29774513
• Heavy Atom Count: 30
• Complexity: 743

Purity/Quality:

99% ^*data from raw suppliers

Calcipotriene ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Canonical SMILES: CC(C=CC(C1CC1)O)C2CCC3C2(CCCC3=CC=C4CC(CC(C4=C)O)O)C
• Isomeric SMILES: C[C@H](/C=C/C(C1CC1)O)[C@H]2CC[C@@H]\3[C@@]2(CCC/C3=C\C=C/4\C[C@H](C[C@@H](C4=C)O)O)C
• Recent EU Clinical Trials: Exploratory study of the efficacy and safety of topical bimiralisib in an inflammatory and hyperproliferative skin condition
• Description: Calcipotriene also known as Calcipotriol, is a topical vitaminD3 derivative effective in the treatment of psoriasis vulgaris. The drug acts by binding to vitamin D3 receptors in the skin keratinocytes, producing an elevation in cell differentiation and a reduction in cell proliferation. Although its efficacy is comparable to calcitriol, calcipotriol exhibits at least 100 times less effect on calcium metabolism in rats.
• Uses: Calcipotriene is an antipsoriatic that is a vitamin D3 analogue with low calcemic activity. It works by regulating the production and growth of skin cells. In the United States, this drug was first marketed under the trade name Dovonex and is used mainly for the treatment of psoriasis. It is one of the most effective non glucocorticoid topical drugs for the treatment of localized psoriasis.This drug has many off-label applications that are alternative therapies for many dermatologic diseases.
• Indications: Calcipotriene (Dovonex), a synthetic vitamin D3 derivative, is indicated for the treatment of moderate plaque psoriasis. Its mechanism of action is unknown, although it competes for calcitriol receptors on keratinocytes and normalizes differentiation. It also has a variety of immunomodulatory effects in the skin. Although the drug can cause local irritation, the most serious toxicities are hypercalciuria and hypercalcemia, which are usually reversible.
• Therapeutic Function: Antipsoriatic

Technology Process of (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol

There total 46 articles about (1R,3S,5Z)-5-[(2E)-2-[(1R,3aS,7aR)-1-[(E,2R)-5-cyclopropyl-5-hydroxypent-3-en-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 87.0%

(1S,3R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10(19)-triene (112875-61-3,134523-61-8,910133-69-6,910133-34-5) → calcipotriene (112965-21-6)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20 ℃;

DOI:10.1016/j.jsbmb.2010.03.074

Reference yield:

→ betamethasone dipropionate (5593-20-4) + calcipotriene (112965-21-6)

Guidance literature:

Reference yield:

(5Z,7E,22E)-(1S,3R)-1,3-bis(tert-butyldimethylsilyloxy)-24S-cyclopropyl ethyl carbonate benzyl ester-9,10-secochola-5,7,10(19),22-tetraene → calcipotriene (112965-21-6)

Guidance literature:

(5Z,7E,22E)-(1S,3R)-1,3-bis(tert-butyldimethylsilyloxy)-24S-cyclopropyl ethyl carbonate benzyl ester-9,10-secochola-5,7,10⁽¹⁹⁾,22-tetraene; With anthracene; triethylamine; In toluene; for 1.5h; UV-irradiation;

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 60 ℃; for 1h;

With palladium 10% on activated carbon; hydrogen; In tetrahydrofuran; at 20 ℃; for 3h; under 760.051 Torr;

upstream raw materials:

(1S,3R)-bis(tert-butyldimethylsilyloxy)-20(R)-(3'(S)-cyclopropyl-3'-hydroxyprop-1'(E)-enyl)-9,10-secopregna-5(Z),7(E),10⁽¹⁹⁾-triene

Cyclopropyl methyl ketone

2-bromo-1-cyclopropylethan-1-one

1-cyclopropyl-2-(triphenyl-λ⁵-phosphanylidene)ethan-1-one

Downstream raw materials:

calci-dioxole

calcipotriol monohydrate

Refernces

• 1、 Rumbo, Antonio,Perez-Garcia, Xenxo,Mourino, Antonio. "Stereoselective synthesis of C24-hydroxylated vitamin D3 analogs: A practical and expeditius route to calcipotriol". scheme or table. p. 68 - 70. Retrieved 2011/11/14.
• 2、 -. "ISOMERISATION OF PHARMACEUTICAL INTERMEDIATES". Page/Page column 20-21. . Retrieved 2008/06/13.