Falecalcitriol

Base Information

• Chemical Name: Falecalcitriol
• CAS No.: 83805-11-2
• Molecular Formula: C27H38F6O3
• Molecular Weight: 524.587
• UNII: G70A8514T8
• ChEMBL ID: CHEMBL2106158
• DSSTox Substance ID: DTXSID601027560
• Metabolomics Workbench ID: 35640
• NCI Thesaurus Code: C80884
• Nikkaji Number: J1.369.083I
• Wikidata: Q5431843
• Wikipedia: Falecalcitriol
• Mol file: 83805-11-2.mol

Synonyms:1,25-dihydroxy-26,27-hexafluorocholecalciferol;26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3;26,27-F6-1,25(OH)2-Vit D3;26,27-F6-1,25-dihydroxyvitamin D3;calcitriol hexafluoride;F(6)-1,25(OH)2 vitamin D3;F6-1,25(OH)2D3;falecalcitriol;hexafluorocalcitriol;ST 630;ST-630

Chemical Property of Falecalcitriol

Chemical Property:

• Vapor Pressure: 1.03E-15mmHg at 25°C
• Refractive Index: 1.504
• Boiling Point: 576.9 °C at 760 mmHg
• Flash Point: 302.7 °C
• PSA: 60.69000
• Density: 1.24 g/cm³
• LogP: 6.78950
• XLogP3: 6.6
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 6
• Exact Mass: 524.27251404
• Heavy Atom Count: 36
• Complexity: 860

Purity/Quality:

98%,99%, ^*data from raw suppliers

Falecalcitriol ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(CCCC(C(F)(F)F)(C(F)(F)F)O)C1CCC2C1(CCCC2=CC=C3CC(CC(C3=C)O)O)C
• Isomeric SMILES: C[C@H](CCCC(C(F)(F)F)(C(F)(F)F)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C
• Recent NIPH Clinical Trials: Effects of falecalcitoriol on post-operative hypoparathyroidism after thyroidectomy
• Description: Falecalcitriol, previously known as flocalcitrol, was launched by several codevelopers in Japan for the treatment of secondary hyperthyroidism (SHPT). This hexafluorinated analog of 1α,25-dihydroxyvitamin D3 (calcitriol), the hormonally active form of vitamin D3, can be obtained by several different synthetic routes from a conveniently protected cholestenol, a key step being an aldol reaction with hexafluoroacetone. Falecalcitriol is several times more active than 1,25(OH)2D3 in regulating the proliferation of parathyroid cells and parathyroid hormone (PTH) synthesis that are believed to be mediated through binding to VDR, a nuclear receptor for vitamin D; furthermore, it was proposed that a bioactive 23S-hydroxylated metabolite, resistant to further metabolism, contributes to the retention of an active compound for longer in cells and so, to significantly lengthen the duration of action. In a comparative clinical study conducted in hemodialysis patients with moderate to severe SHPT, falecalcitriol was found to be more active than alfacalcidol in suppressing parathyroid hormone without triggering hypercalcemia.
• Uses: Hexafluorinated analog of Calcitriol (C144500). A more potent therapeutic agent for secondary hyperparathyroidism.

Technology Process of Falecalcitriol

There total 33 articles about Falecalcitriol 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: 90.0%

26,26,26,27,27,27-hexafluoro-1α,25-dihydroxycholecalciferol triacetate → Falecalcitriol (83805-11-2)

Guidance literature:

With potassium hydroxide; In tetrahydrofuran; methanol; for 14h; Ambient temperature; in the dark;

DOI:10.1248/cpb.30.4297

Reference yield: 56.0%

(5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-25-methoxymethoxy-9,10-seco-5,7,10(19)-cholestatriene (163392-53-8) → Falecalcitriol (83805-11-2)

Guidance literature:

With methanesulfonic acid; In methanol; at 20 ℃; for 2h;

DOI:10.1016/S0968-0896(00)00142-5

Reference yield:

(5Z,7E,20R)-1α,3β-bis<(tert-butyldimethylsilyl)oxy>-20-formylmethyl-9,10-seco-5,7,10(19)-pregnatriene (143884-26-8) → Falecalcitriol (83805-11-2)

Guidance literature:

Multi-step reaction with 10 steps

1.1: 91 percent / tetrahydrofuran; diethyl ether / 0.5 h / 0 °C

2.1: 92 percent / NMO; 4 Angstroem MS / tetrapropylammonium perrutenate / CH₂Cl₂ / 0.25 h / 20 °C

3.1: 82 percent / LiN(TMS)2 / tetrahydrofuran / 0.5 h / -70 °C

4.1: 52 percent / NaBH₄ / tetrahydrofuran; methanol / 0.17 h / -10 °C

5.1: 97 percent / pyridine / 12 h / 20 °C

6.1: 89 percent / iPr₂NEt / CHCl₃ / 1 h / Heating

7.1: 94 percent / 5 percent KOH / methanol / 1 h / 0 °C

8.1: NaH; imidazole / tetrahydrofuran / 20 °C

8.2: 80 percent / 2 h / 20 °C

9.1: 97 percent / nBu₃SnH / toluene / 1 h / Heating

10.1: 56 percent / MsOH / methanol / 2 h / 20 °C

With 1H-imidazole; potassium hydroxide; sodium tetrahydroborate; N-methyl-2-indolinone; methanesulfonic acid; 4 Angstroem MS; tri-n-butyl-tin hydride; sodium hydride; N-ethyl-N,N-diisopropylamine; lithium hexamethyldisilazane; tetrapropylammonium perruthennate; In tetrahydrofuran; pyridine; methanol; diethyl ether; dichloromethane; chloroform; toluene; 1.1: Grignard reaction / 2.1: Oxidation / 3.1: Condensation / 4.1: Reduction / 5.1: Acetylation / 6.1: Alkylation / 7.1: Deacetylation / 8.1: thiocarbonylation / 8.2: Methylation / 9.1: Reduction / 10.1: Hydrolysis;

DOI:10.1016/S0968-0896(00)00142-5

upstream raw materials:

(5Z,7E)-(1S,3R)-1,3-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-25-methoxymethoxy-9,10-seco-5,7,10⁽¹⁹⁾-cholestatriene

(5Z,7E,20R)-1α,3β-bis<(tert-butyldimethylsilyl)oxy>-20-formylmethyl-9,10-seco-5,7,10(19)-pregnatriene

1α,3β-bis[(t-butyldimethylsilyl)oxy]-20(S)-(n-propyl-23-oxo)-9,10-secopregna-5(Z),7(E),10(19)-triene

1α,3β-bis[(t-butyldimethylsilyl)oxy]-26,26,26,27,27,27-hexafluoro-23-oxo-9,10-secocholesta-5(Z),7(E),10(19)-trien-25-ol

Downstream raw materials:

(6Z)-(1R,3R)-26,26,26,27,27,27-hexafluoro-9,10-seco-5(10),6,8-cholestatriene-1β,3β,25-triol

(6Z)-(3R)-26,26,26,27,27,27-hexafluoro-9,10-seco-5⁽¹⁰⁾,6,8-cholestatriene-3,25-diol-1-one

Refernces

• 1、 Igarashi, Jun-Etsu,Ikeda, Masahiko,Sunagawa, Makoto. "Kinetics of thermal [1,7A]-sigmatropic shift of hexafluoro vitamin D3 and vitamin D3 derivatives. Evaluation of conformations of the A ring affected by 1-OH and 3-OH groups". . p. 1431 - 1436. Retrieved 2007/10/03.
• 2、 Kobayashi,Taguchi,Mitsuhashi,et al.. "Studies on organic fluorine compounds. XXXIX. Studies on steroids. LXXIX. Synthesis of 1α,25-dihydroxy-26,26,26,27,27,27-hexafluorovitamin D3". . p. 4297 - 4303. Retrieved 2007/10/02.