Eldecalcitol

Base Information

• Chemical Name: Eldecalcitol
• CAS No.: 104121-92-8
• Molecular Formula: C30H50O5
• Molecular Weight: 490.724
• UNII: I2JP8UE90H
• Wikipedia: Eldecalcitol
• NCI Thesaurus Code: C87291
• Pharos Ligand ID: UTYAZWAWL8XU
• Metabolomics Workbench ID: 36020
• ChEMBL ID: CHEMBL4297608
• Mol file: 104121-92-8.mol

Synonyms:2-(3-hydroxypropoxy)-1,25-dihydroxyvitamin D3;2-(3-hydroxypropoxy)calcitriol;20-epi-1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3;20-epi-ED-71;20-epi-eldecalcitol;ED 71;ED-71;eldecalcitol

Chemical Property of Eldecalcitol

Chemical Property:

• Vapor Pressure: 5.68E-20mmHg at 25°C
• Melting Point: 126-128 °C
• Refractive Index: 1.55
• Boiling Point: 655.656 °C at 760 mmHg
• PKA: 13.80±0.60(Predicted)
• Flash Point: 350.328 °C
• PSA: 90.15000
• Density: 1.105 g/cm³
• LogP: 5.08220
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 4
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 10
• Exact Mass: 490.36582469
• Heavy Atom Count: 35
• Complexity: 784

Purity/Quality:

99%min ^*data from raw suppliers

Eldecalcitol ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC(CCCC(C)(C)O)C1CCC2C1(CCCC2=CC=C3CC(C(C(C3=C)O)OCCCO)O)C
• Isomeric SMILES: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H]([C@H]([C@@H](C3=C)O)OCCCO)O)C
• Recent ClinicalTrials: Comparison of Efficacy of Denosumab With Eldecalcitol or Native Vitamin D in Postmenopausal Women With Osteoporosis.
• Recent NIPH Clinical Trials: The combination therapy with Eldecalcitol and Ibandronate sodium
• Description: Eldecalcitol (Edirol) was approved in January 2011 by the Japanese Ministry of Health, Labor, and Welfare for the treatment of osteoporosis. Because of vitamin D’s central role in the bone health, vitamin D and analogs of vitamin D have been used to treat patients diagnosed with osteoporosis. Eldecalcitol is an analog of the active form of vitamin D, calcitriol, in which the lower cyclohexane ring contains a hydroxypropyl group. The synthesis of eldecalcitol involves the assembly of two units, a fully protected (3S,4S,5R)-oct-1-en-7-yne-3,4,5-triol and a fused bicyclic system, (R)-6- ((1R,3aR,7aR,E)-4-(bromomethylene)-7a-methyloctahydro-1H-inden-1- yl)-2-methylheptan-2-ol, through a Diels-Alder reaction to give fully protected eldecalcitol. The hydroxyl groups are then deprotected to give the parent molecule. Eldecalcitol binds to the vitaminDreceptor 2.7-fold more potently than calcitriol, while only weakly inhibiting serum parathyroid hormone.
• Uses: Eldecalcitol is a derivative of vitamin D3 (V676045) which is the vitamin that mediates intestinal calcium absorbtion, bone calcium metabolism and probably, muscle activity.
• Clinical Use: Eldecalcitol is a vitamin D3 analog approved in Japan for the treatment of osteoporosis. Itwasdiscoveredby Chugai and co-developed with Taisho. Eldecalcitol, a hormonally active calcitrol analog, regulates calcium and bone metabolism. The drug was approved on the basis of results from randomized, double-blinded, parallelgroup, phase III studies taking place over three years that showed eldecalcitol to significantly lower incidence of new vertebral fractures compared to those receiving the comparator drug alfacalcidol. Discovery and SAR studies of vitamin D3 analogs leading to the identification of eldecalcitol have been reported. In addition, multiple syntheses, including parallel approaches, have been reported in publications and patents.

Technology Process of Eldecalcitol

There total 93 articles about Eldecalcitol 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: 96.0%

(1β,2α,3α,5Z,7E)-1,3-bis[(1,1-dimethylethyl)dimethylsilyloxy]-2-[3-[(1,1-dimethylethyl)dimethylsilyloxy]propoxy]-25-trimethylsilyloxy-9,10-secocholesta-5,7,10(19)-triene (342645-84-5) → Eldecalcitol (104121-92-8)

Guidance literature:

With pyridine; hydrogen fluoride; In tetrahydrofuran; at 20 ℃;

DOI:10.1021/ja003976k

Reference yield: 89.0%

C54H106O5Si4 → Eldecalcitol (104121-92-8)

Guidance literature:

With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 25 ℃;

Reference yield: 80.0%

((1R,2R,3R,Z)-2-(3-(tert-butyldiphenylsilyloxy)propoxy)-5-((E)-2-((1R,3aS,7aR)-7a-methyl-1-((R)-6-methyl-6-(trimethylsilyloxy)heptan-2-yl)dihydro-1H-indene-4(2H,5H,6H,7H,7aH)-ylidene)ethylidene)-4-methylene cyclohexane-1,3-diyl)bis(oxy)bis(tert-butyldimethylsilane) → Eldecalcitol (104121-92-8)

Guidance literature:

With toluene-4-sulfonic acid; In methanol; dichloromethane; at 20 ℃; for 5h; Inert atmosphere;

DOI:10.1021/acs.oprd.0c00436

upstream raw materials:

25-[(triethylsilyl)oxy]de-A,B-cholestan-8-one

[3R-(1Z,3β,4α,5α)]-[2-[3,5-bis[(1,1-dimethylethyl)dimethylsilyloxy]-4-[3-[(1,1-dimethylethyl)dimethylsilyloxy]propoxy]-2-methylenecyclohexylidene]ethyl]diphenylphosphine oxide

(1β,2α,3α,5Z,7E)-1,3-bis[(1,1-dimethylethyl)dimethylsilyloxy]-2-[3-[(1,1-dimethylethyl)dimethylsilyloxy]propoxy]-25-trimethylsilyloxy-9,10-secocholesta-5,7,10(19)-triene

(5Z,7E)-(1R,2R,3R)-1,3-bis(tert-butyldimethylsilyloxy)-2-(3-tert-butyldimethylsilyloxypropoxy)-25-triethylsilyloxy-9,10-secocholesta-5,7,10⁽¹⁹⁾-triene

Refernces

• 1、 -. "PROCESS AND INTERMEDIATES FOR THE PREPARATION OF ELDECALCITOL". . . Retrieved 2020/12/01.
• 2、 Zhao, Guo-Dong,Liu, Zhao-Peng. "Structural revisions of the reported A-ring phosphine oxide synthon for ED-71 (Eldecalcitol) and a new synthesis". . p. 8033 - 8040. Retrieved 2015/12/31.