57333-96-7

Basic information

• Product Name: Tacalcitol
• Synonyms: (1α，3β-5Z，7E，24R)-9，10-Secoholesta-5，7，10(19)-triene-1，3，24-triol;lα，24-Dihydroxycholecalciferol;lα，24R-Dihy-droxyvitamin D3;[5Z,7E,24R,(+)]-9,10-Secocholesta-5,7,10(19)-triene-1α,3β,24-triol;1α,24(R)-Dihydroxyvitamin D3;1α,24R-Dihydroxyvitamin D3;(1a,3b,5Z,7E,24R)-9,10-Secocholesta-5,7,10(19)-triene-1,3,24-triol;C12919
• CAS NO: 57333-96-7
• Molecular Formula: C₂₇H₄₄O₃
• Molecular Weight: 416.63646
• Product Categories: Vitamin D3 analogs
• Mol File: 57333-96-7.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 565 °C at 760 mmHg
• Flash Point: 238.4 °C
• Appearance: /
• Density: 1.06
• Vapor Pressure: 4.05E-15mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: Store at -20°C
• PKA: 14.43±0.40(Predicted)
• CAS DataBase Reference: Tacalcitol(CAS DataBase Reference)
• NIST Chemistry Reference: Tacalcitol(57333-96-7)
• EPA Substance Registry System: Tacalcitol(57333-96-7)

Safety Data

• Hazardous Substances Data: 57333-96-7(Hazardous Substances Data)

Usage

Description

Tacalcitol is a vitamin D analog developed as a topical antipsoriatic medication, specifically designed to treat various skin conditions such as keratosis, psoriasis, ichthyosis, pityriasis rubra pilaris, palmoplantar pustulosis, and keratoderma. It has demonstrated significant improvement in the appearance of skin lesions for psoriasis patients without causing significant side effects. Tacalcitol effectively inhibits keratinocyte growth in patients with psoriasis vulgaris and has shown to suppress interleukin-1-α-induced granulocyte macrophage colony-stimulating-factor mRNA expression in human dermal microvascular endothelial cells, potentially playing a role in mediating angioproliferation in skin inflammation. It is commercially available under the brand name Bonalfa.

Uses

Used in Dermatology:
Tacalcitol is used as a topical antipsoriatic agent for the treatment of various skin conditions, including keratosis, psoriasis, ichthyosis, pityriasis rubra pilaris, palmoplantar pustulosis, and keratoderma. It helps improve the appearance of skin lesions in psoriasis patients and effectively inhibits keratinocyte growth, providing relief from the symptoms of these skin conditions.
Used in Pharmaceutical Industry:
Tacalcitol is used as an active pharmaceutical ingredient in the development of medications for the treatment of skin disorders. Its effectiveness in improving skin lesions and inhibiting keratinocyte growth makes it a valuable component in the formulation of topical antipsoriatic drugs.
Used in Research and Development:
Tacalcitol is used as a research compound for studying the effects of vitamin D analogs on skin health and the underlying mechanisms of various skin conditions. Its ability to inhibit interleukin-1-α-induced granulocyte macrophage colony-stimulating-factor mRNA expression in human dermal microvascular endothelial cells makes it an important tool for understanding the role of angioproliferation in skin inflammation and the potential therapeutic applications of vitamin D analogs in dermatology.

Originator

Teijin (Japan)

Safety Profile

A poison by ingestion, subcutaneous, and intravenous routes. When heated to decomposition it emits acrid smoke and irritating vapors,

InChI:InChI=1/C27H44O3/c1-17(2)25(29)13-8-18(3)23-11-12-24-20(7-6-14-27(23,24)5)9-10-21-15-22(28)16-26(30)19(21)4/h9-10,17-18,22-26,28-30H,4,6-8,11-16H2,1-3,5H3/b20-9+,21-10-/t18-,22-,23-,24+,25-,26+,27-/m1/s1

Synthetic route

((1R,3S,Z)-5-((E)-2-((1R,7aR)-7a-methyl-1((2R,5R)-6-methyl-5-(triethylsilyloxy)heptan-2-yl)dihydro-1H-inden-4(2H,5H,6H,7H,7aH)-ylidene)ethylidene)-4-methylenecyclohexane-1,3-diyl)bis(oxy)bis(tert-butyldimethylsilane) → tacalcitol (57333-96-7)

Conditions	Yield
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; Darkness;	98%
With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 40h; Darkness;	98%

(1R,3S)-5-[2-[(1R,3aS,7aR)-1-((1R,4R)-4-Methoxymethoxy-1,5-dimethyl-hexyl)-7a-methyl-octahydro-inden-(4E)-ylidene]-eth-(Z)-ylidene]-4-methylene-cyclohexane-1,3-diol → tacalcitol (57333-96-7)

Conditions	Yield
With hydrogen fluoride In water; acetonitrile at 20℃; for 24h;	76%
With methanol; AG 50W-X4 resin at 20℃; methanolysis;	33 mg

C41H74O4Si2 → tacalcitol (57333-96-7)

Conditions	Yield
Stage #1: C41H74O4Si2 With potassium carbonate In methanol at 20℃; for 5h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran for 2h; Reflux;	75%

C46H76O4Si2 → tacalcitol (57333-96-7)

Conditions	Yield
Stage #1: C46H76O4Si2 With potassium carbonate In methanol at 20℃; for 5h; Stage #2: With tetrabutyl ammonium fluoride In tetrahydrofuran for 2h; Reflux;	75%

C39H72O3Si2 → tacalcitol (57333-96-7)

Conditions	Yield
With (1S)-10-camphorsulfonic acid In methanol; chloroform at 20℃; for 2.5h;	65%
Stage #1: C39H72O3Si2 With tetrabutyl ammonium fluoride In tetrahydrofuran at 50 - 55℃; for 2h; Stage #2: With maleic anhydride In ethyl acetate at 30 - 35℃; for 24h;	300 mg

1α,3β,24(R)-trihydroxycholesta-5,7-diene (57701-47-0) → tacalcitol (57333-96-7)

Conditions	Yield
In diethyl ether Irradiation;

(S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate (66774-80-9) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 13 steps 1.1: 91 percent / dimethylsulfoxide / 2 h / 90 °C 2.1: 98 percent / imidazole / dimethylformamide / 12 h / 80 °C 3.1: lithium diisopropylamide / tetrahydrofuran; hexane / 1 h / -78 - 0 °C 3.2: 91 percent / hexamethylphosphoramide / tetrahydrofuran; hexane / 7 h / -60 - 20 °C 4.1: 94 percent / tert-butanol; potassium; hexamethylphosphoramide / diethyl ether / 13 h / 0 - 20 °C 5.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 6.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 7.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 8.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 8.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 9.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 10.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 11.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 12.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 13.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

(8S,20S)-de-A,B-20-(hydroxymethyl)pregnan-8-ol (64190-52-9) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 14 steps 1.1: 93 percent / pyridine / 12 h / 0 °C 2.1: 91 percent / dimethylsulfoxide / 2 h / 90 °C 3.1: 98 percent / imidazole / dimethylformamide / 12 h / 80 °C 4.1: lithium diisopropylamide / tetrahydrofuran; hexane / 1 h / -78 - 0 °C 4.2: 91 percent / hexamethylphosphoramide / tetrahydrofuran; hexane / 7 h / -60 - 20 °C 5.1: 94 percent / tert-butanol; potassium; hexamethylphosphoramide / diethyl ether / 13 h / 0 - 20 °C 6.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 7.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 8.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 9.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 9.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 10.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 11.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 12.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 13.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 14.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme
Multi-step reaction with 11 steps 1: 1H-imidazole; dmap / N,N-dimethyl-formamide / 96 h / 20 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 12 h / 20 °C 3: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 12 h / 0 - 20 °C 4: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 12 h / 0 - 20 °C 5: lithium hexamethyldisilazane / tetrahydrofuran / 15 h / -78 - 20 °C 6: tetrabutyl ammonium fluoride / tetrahydrofuran / 17 h / 65 °C 7: hydrogen; palladium 10% on activated carbon / methanol / 15 h 8: dipyridinium dichromate / dichloromethane / 20 °C 9: n-butyllithium / tetrahydrofuran / 18 h / -78 °C 10: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Darkness 11: hydrogen fluoride / acetonitrile; water / 24 h / 20 °C View Scheme
Multi-step reaction with 10 steps 1.1: 1H-imidazole / N,N-dimethyl-formamide / 50 - 55 °C 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / -5 - 5 °C 3.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; potassium bromide; sodium hypochlorite; sodium hydrogencarbonate / dichloromethane; water / 0.17 h / -5 - 5 °C 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -70 - -60 °C 4.2: -70 - 20 °C 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 55 - 60 °C 6.1: pyridinium chlorochromate / dichloromethane / 20 °C 7.1: palladium 10% on activated carbon; hydrogen / tetrahydrofuran; methanol / 24 h / 2280.15 - 2660.18 Torr 8.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C 9.1: n-butyllithium / tetrahydrofuran / 1 h / -70 - -60 °C 9.2: 1.5 h / -65 - -10 °C 10.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Darkness View Scheme
Multi-step reaction with 10 steps 1.1: 1H-imidazole; ammonium chloride / N,N-dimethyl-formamide / 50 - 55 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere 3.1: 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene / dichloromethane / 4 h / 20 °C / Inert atmosphere 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 0.5 h / -70 °C / Inert atmosphere 4.2: -70 - 20 °C / Inert atmosphere 5.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 60 °C / Inert atmosphere 6.1: dipyridinium dichromate / dichloromethane / 20 °C 7.1: palladium 10% on activated carbon; hydrogen / tetrahydrofuran; methanol / 24 h / 2280.15 - 2660.18 Torr 8.1: 1H-imidazole / N,N-dimethyl-formamide / 2 h / 20 °C / Inert atmosphere 9.1: n-butyllithium / tetrahydrofuran / 1 h / -65 °C / Inert atmosphere 9.2: 1.5 h / -65 - -10 °C / Inert atmosphere 10.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 40 h / 20 °C / Darkness View Scheme

<1R-<1β(R*),3aα,4β,7aβ>>-octahydro-4-hydroxy-β,7a-dimethyl-1H-indene-1-propanenitrile (93489-60-2) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 12 steps 1.1: 98 percent / imidazole / dimethylformamide / 12 h / 80 °C 2.1: lithium diisopropylamide / tetrahydrofuran; hexane / 1 h / -78 - 0 °C 2.2: 91 percent / hexamethylphosphoramide / tetrahydrofuran; hexane / 7 h / -60 - 20 °C 3.1: 94 percent / tert-butanol; potassium; hexamethylphosphoramide / diethyl ether / 13 h / 0 - 20 °C 4.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 5.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 6.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 7.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 7.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 8.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 9.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 10.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 11.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 12.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

De-A,B-(24R)-8β-[(tert-butyldimethylsilyl)oxy]-cholestan-24-ol (145223-31-0) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 9 steps 1.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 2.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 3.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 4.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 4.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 5.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 6.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 7.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 8.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 9.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

(R)-3-((1R,3aR,4S,7aR)-4-((tert-butyldimethylsilyl)oxy)-7a-methyloctahydro-1H-inden-1-yl)butanenitrile (145223-29-6) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 11 steps 1.1: lithium diisopropylamide / tetrahydrofuran; hexane / 1 h / -78 - 0 °C 1.2: 91 percent / hexamethylphosphoramide / tetrahydrofuran; hexane / 7 h / -60 - 20 °C 2.1: 94 percent / tert-butanol; potassium; hexamethylphosphoramide / diethyl ether / 13 h / 0 - 20 °C 3.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 4.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 5.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 6.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 6.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 7.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 8.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 9.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 10.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 11.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

De-A,B-(24R,22ξ)-8β-[(tert-butyldimethylsilyl)oxy]-24-hydroxy-cholestane-22-carbonitrile (145223-30-9) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 10 steps 1.1: 94 percent / tert-butanol; potassium; hexamethylphosphoramide / diethyl ether / 13 h / 0 - 20 °C 2.1: 93 percent / N,N-diisopropylethylamine / CH2Cl2 / 0 - 20 °C 3.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 4.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 5.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 5.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 6.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 7.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 8.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 9.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 10.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

De-A,B-(24R)-24-[(methoxymethyl)oxy]-cholestan-8-one (188949-00-0) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 1.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 2.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 3.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 4.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 5.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 6.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran / 18 h / -78 °C 2: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Darkness 3: hydrogen fluoride / acetonitrile; water / 24 h / 20 °C View Scheme

De-A,B-(24R)-8β-hydroxy-cholestan-24-ol methoxymethyl ether (188948-99-4) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 2.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 2.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 3.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 4.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 5.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 6.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 7.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme
Multi-step reaction with 4 steps 1: dipyridinium dichromate / dichloromethane / 20 °C 2: n-butyllithium / tetrahydrofuran / 18 h / -78 °C 3: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Darkness 4: hydrogen fluoride / acetonitrile; water / 24 h / 20 °C View Scheme

De-A,B-(24R)-24-[(methoxymethyl)oxy]-cholest-8-en-8-yl trifluoromethanesulfonate (188948-96-1) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 2: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 3: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 4: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 5: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

De-A,B-(24R)-8β-[(tert-butyldimethylsilyl)oxy]-cholestan-24-ol methoxymethyl ether (188948-98-3) → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 8 steps 1.1: 97 percent / tetrabutylammonium fluoride / tetrahydrofuran / 18 h / Heating 2.1: 96 percent / pyridinium dichromate; pyridinium p-toluenesulfonate / CH2Cl2 / 40 h / 0 °C 3.1: lithium diisopropylamide / hexane; tetrahydrofuran / 2 h / -78 - 20 °C 3.2: 76 percent / tetrahydrofuran; hexane / -78 - 20 °C 4.1: 92 percent / Et3N / bis-triphenylphosphine palladium dichloride / dimethylformamide / 2 h / 70 °C 5.1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 6.1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 7.1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 8.1: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

(24R)-1α-[(tert-butyldimethylsilyl)oxy]-6,7-didehydro-24-[(methoxymethyl)oxy]-previtamin D3 tert-butyldimethylsilyl ether (188948-95-0) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: 83 percent / hydrogen; quinoline / Lindlar catalyst / hexane / 0.5 h 2: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 3: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 4: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

1α-[(tert-butyldimethylsilyl)oxy]-24R-[(methoxymethyl)oxy]-previtamin D3 tert-butyldimethylsilyl ether (188949-01-1) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / 2,2,4-trimethyl-pentane / 4 h / Heating 2: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 3: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme

1α-[(tert-butyldimethylsilyl)oxy]-24R-[(methoxymethyl)oxy]-vitamin D3 tert-butyldimethylsilyl ether (188949-02-2) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrabutylammonium fluoride / tetrahydrofuran / 20 h / 20 °C 2: 33 mg / AG 50W-X4 resin; methanol / 20 °C View Scheme
Multi-step reaction with 2 steps 1: tetrabutyl ammonium fluoride / tetrahydrofuran / 20 °C / Darkness 2: hydrogen fluoride / acetonitrile; water / 24 h / 20 °C View Scheme

1α, 3β, 24-trihydroxycholest-5-ene (59780-19-7) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: Py 3: diethyl ether / Irradiation View Scheme

1α, 2α-epoxy-24-keto-cholesta-4,6-dien-3-one (57701-42-5) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: Li, NH4Cl, liq. NH3 2: Py 4: diethyl ether / Irradiation View Scheme

1α-Hydroxy-3β,24(R)-dibenzoyloxy-cholest-5-ene (57333-97-8) → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 2 steps 2: diethyl ether / Irradiation View Scheme

C24H46O2Si → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: dichloromethane / 4 h / 0 - 20 °C / Inert atmosphere 2.1: palladium on activated charcoal; hydrogen / methanol / 760.05 Torr 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 4.1: pyridinium dichromate; aluminum oxide / dichloromethane / 20 h / 20 °C 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 5.2: 2 h / 20 °C 6.1: potassium carbonate / methanol / 5 h / 20 °C 6.2: 2 h / Reflux View Scheme

C34H50O2Si → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 6 steps 1.1: pyridine / dichloromethane / 5 h / 0 - 20 °C / Inert atmosphere 2.1: palladium on activated charcoal; hydrogen / methanol / 760.05 Torr 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 4.1: pyridinium dichromate / dichloromethane / 20 h / 20 °C / Inert atmosphere 5.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 5.2: 2 h / 20 °C 6.1: potassium carbonate / methanol / 5 h / 20 °C 6.2: 2 h / Reflux View Scheme

C26H48O3Si → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: palladium on activated charcoal; hydrogen / methanol / 760.05 Torr 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 3.1: pyridinium dichromate; aluminum oxide / dichloromethane / 20 h / 20 °C 4.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 4.2: 2 h / 20 °C 5.1: potassium carbonate / methanol / 5 h / 20 °C 5.2: 2 h / Reflux View Scheme

C41H54O3Si → tacalcitol (57333-96-7)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: palladium on activated charcoal; hydrogen / methanol / 760.05 Torr 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 3.1: pyridinium dichromate / dichloromethane / 20 h / 20 °C / Inert atmosphere 4.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 4.2: 2 h / 20 °C 5.1: potassium carbonate / methanol / 5 h / 20 °C 5.2: 2 h / Reflux View Scheme

C26H50O3Si → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 2.1: pyridinium dichromate; aluminum oxide / dichloromethane / 20 h / 20 °C 3.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 3.2: 2 h / 20 °C 4.1: potassium carbonate / methanol / 5 h / 20 °C 4.2: 2 h / Reflux View Scheme

C41H56O3Si → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 10 h / Reflux 2.1: pyridinium dichromate / dichloromethane / 20 h / 20 °C / Inert atmosphere 3.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 3.2: 2 h / 20 °C 4.1: potassium carbonate / methanol / 5 h / 20 °C 4.2: 2 h / Reflux View Scheme

C20H36O3 → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium dichromate; aluminum oxide / dichloromethane / 20 h / 20 °C 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 2.2: 2 h / 20 °C 3.1: potassium carbonate / methanol / 5 h / 20 °C 3.2: 2 h / Reflux View Scheme

C25H38O3 → tacalcitol (57333-96-7)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: pyridinium dichromate / dichloromethane / 20 h / 20 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 0.5 h / -60 °C / Inert atmosphere 2.2: 2 h / 20 °C 3.1: potassium carbonate / methanol / 5 h / 20 °C 3.2: 2 h / Reflux View Scheme

tacalcitol (57333-96-7) → 1α,24(R)-dihydroxy-6,19-dihydro-6,19-epidioxyvitamin D3

Conditions	Yield
With oxygen; rose bengal In ethanol for 1h; Irradiation; Yield given;

Upstream product

• 57701-47-0 1α,3β,24(R)-trihydroxycholesta-5,7-diene 
• 66774-80-9 (S)-2-((3R,3aR,7S,7aR)-octahydro-7-hydroxy-3a-methyl-1H-inden-3-yl)propyl 4-methylbenzenesulfonate 
• 64190-52-9 (8S,20S)-de-A,B-20-(hydroxymethyl)pregnan-8-ol 
• 93489-60-2 <1R-<1β(R*),3aα,4β,7aβ>>-octahydro-4-hydroxy-β,7a-dimethyl-1H-indene-1-propanenitrile 
• 145223-31-0 De-A,B-(24R)-8β-[(tert-butyldimethylsilyl)oxy]-cholestan-24-ol 
• 145223-29-6 (R)-3-((1R,3aR,4S,7aR)-4-((tert-butyldimethylsilyl)oxy)-7a-methyloctahydro-1H-inden-1-yl)butanenitrile 
• 145223-30-9 De-A,B-(24R,22ξ)-8β-[(tert-butyldimethylsilyl)oxy]-24-hydroxy-cholestane-22-carbonitrile 
• 188949-00-0 De-A,B-(24R)-24-[(methoxymethyl)oxy]-cholestan-8-one 
• 188948-99-4 De-A,B-(24R)-8β-hydroxy-cholestan-24-ol methoxymethyl ether 
• 188948-96-1 De-A,B-(24R)-24-[(methoxymethyl)oxy]-cholest-8-en-8-yl trifluoromethanesulfonate 
• 188948-98-3 De-A,B-(24R)-8β-[(tert-butyldimethylsilyl)oxy]-cholestan-24-ol methoxymethyl ether 
• 188948-95-0 (24R)-1α-[(tert-butyldimethylsilyl)oxy]-6,7-didehydro-24-[(methoxymethyl)oxy]-previtamin D₃ tert-butyldimethylsilyl ether 
• 188949-01-1 1α-[(tert-butyldimethylsilyl)oxy]-24R-[(methoxymethyl)oxy]-previtamin D₃ tert-butyldimethylsilyl ether 
• 188949-02-2 1α-[(tert-butyldimethylsilyl)oxy]-24R-[(methoxymethyl)oxy]-vitamin D₃ tert-butyldimethylsilyl ether 

Relevant articles and documents

Process Development of Tacalcitol

A highly convergent, gram-scale synthesis of vitamin D3 analogue tacalcitol 1 is disclosed, starting from L-valine and Inhoffen-Lythgoe diol. Key features of the synthesis include modified Julia olefination reaction of β-oxybenzothiazol-2-yl sulfone with C/D ring containing aldehyde to access decagrams of fully functionalized C/D ring synthon. The Horner-Wadsworth-Emmons (HWE) reaction between the C/D ring fragment and commercially available phosphonate completes the carbo-skeleton, which is elaborated into tacalcitol 1 in a gram-scale synthesis.

Process for Preparing Tacalcitol and Intermediate Therefor

The present invention relates to a process for preparing tacalcitol and an intermediate body used therefor. According to the preparation method of the present invention, tacalcitol can be effectively and economically prepared without a complex and long preparation process.COPYRIGHT KIPO 2018

A he cassie is mellow method for the preparation of

The invention discloses a method for preparing tacalcitol. The method comprises the following steps: with a compound I as a starting raw material, carrying out Wittig reaction, CBS catalytic asymmetric reduction, hydroxy protection, hydrogenation reduction, desilication ether protection and oxidation reaction to prepare a compound VIII, carrying out Wittig Horner reaction on the compound VIII and a known compound IX for coupling, and carrying out dehydroxylation protection to obtain the target compound, namely tacalcitol. With cheap raw materials as the starting point, the method disclosed by the invention is simple, convenient and safe, steps unfavorable to amplification, such as illumination reaction and sodium amalgam reduction reaction, are avoided, and industrial production is facilitated.