19356-17-3 Usage
Description
Calcifediol (synonym 25-Hydroxyvitamin D3) is a vitamin D analog and the major metabolite of vitamin D3 (Cholecalciferol) in the liver. Its main function is the regulation of calcium and phosphorus, which is necessary for strong bones. It is used to treat patients with serious kidney diseases to decrease the parathyroid hormone (PTH) level. It is used to treat rickets and osteomalacia, both in azotemic and non-azotemic patient. Calcifediol is sold under RAYALDEE? to treat secondary hyperparathyroidism associated with vitamin D insufficiency in stage 3-4 chronic kidney disease.
Therapeutic drug for bone disease
The natural source of Vitamin D in the body depends on ultraviolet rays of sunlight, making the 7-dehydrocholesterol convert into vitamin D3, at first under the action of vitamin D3 hydroxylase in liver vitamin D3 converts into the Calcifediol, vitamin D3 mainly is present in the form of the Calcifediol in the blood, in the kidney the Calcifediol is further converted to 1,25-dihydroxyvitamin D3 (calcitriol for short) and 24,25-dihydroxyvitamin D3, activity of calcitriol is 2-5 times of the Calcifediol, the two drugs can promote bone re-absorption of calcium and intestinal absorption of Ca2 +. In addition to regulating the body's calcium and phosphorus metabolism, this product can promote the intestinal absorption of calcium and phosphorus, promote calcium and phosphorus deposits in the bone tissue, promote bone formation.
Calcifediol itself has a certain activity, can be used for the treatment of metabolic bone diseases, such as osteoporosis, rickets, osteomalacia, but also for hemodialysis-induced hypocalcemia. Patients with chronic renal failure combined with metabolic bone diseases, engaged during dialysis, can be applied. It can increase the levels of serum calcium, can reduce levels of serum alkaline phosphatase and parathyroid hormone, improve radiological and histological sign of osteitis (with or without osteomalacia). Bone resorption, hyperparathyroidism and osteodystrophy signs of mineralization defects all can be reduced, as for osteomalacia patients and children who are unable to obtain sufficient bone development because of renal osteodystrophy or parathyroid dysfunction, may be more favorable than calcitriol. Such cases can be treated with Calcifediol and calcitriol. But as for osteomalacia accompanied by gastrointestinal diseases, Calcifediol is preferable. If because of liver disease to cause generated obstacles of 25-OHD in vivo, secondary osteomalacia, can also try to use this product. But osteomalacia caused by aluminum poisoning, treatment of vitamin D preparations often is ineffective. Chelator deferoxamine (Desferal) clear aluminum of blood dialysis, can be effective.
Osteomalacia and rickets (in children causing deformities severe osteomalacia) is characterized by obstacle of bone mineralization and non-calcified bone-like tissue or cartilage accumulation. Bone changes of Vitamin D-related bone softening, accompanied with normal or reduced levels of serum calcium and phosphorus, increased serum alkaline phosphatase, and PTH is secondary increased.
Osteoporosis is characterized by reduced bone tissue thereby increasing the likelihood of fractures. Pathological mechanism may be an increased rate of bone resorption, exceeding bone formation; or decreased bone formation, and bone resorption is also still normal or reduced. Bone is progressive missing, can compress and collapse the spine, causing pain, body shorter and kyphosis. Patients are also prone to the outer periphery fracture.
The above information is edited by the lookchem of Liu Yujie.
Side effects and precautions
Like all the vitamin D metabolites, excessive Calcifediol can also cause increased serum calcium, in urine can increase high. Therefore, in the dose adjustment period, serum calcium should be monitored at least once a week, if increased serum calcium was found, it should be discontinued.
Pregnant women use this product, there is no adequately controlled studies, but in experimental animals, teratogenic effects have been found.
The US Food and Drug Administration (FDA) classify the product into pregnancy category C drugs.
People who use digitalis, should be used with caution vitamin D, because increased calcium may induce arrhythmia.
Other side effects and precautions, see "Vitamin D2" (Vita-min D2) that is ergocalciferol.
Action of Vitamin D2 is intense, may cause damage. Increased serum calcium caused by excess, can cause gastrointestinal and central nervous system lesions, soft tissue calcification. Kidney complications can be very serious and even cause death. Such as increased serum calcium persists, after discontinuation, kidney damage likely will continue for a long time. An individual who the amount is not too large, but also because of increased sensitivity to occur adverse reactions.
Calcifediol is rapidly absorbed, at 4 to 8 hours up to serum peak concentration. Transport shall bind with protein, half-life is about 16 days.
References
https://pubchem.ncbi.nlm.nih.gov
https://de.wikipedia.org/wiki/Calcidiol
https://www.webmd.com
https://www.drugbank.ca
Chemical Properties
White Solid
Originator
Dedrogyl,Roussel,France,1976
Uses
Different sources of media describe the Uses of 19356-17-3 differently. You can refer to the following data:
1. 25-Hydroxyvitamin D3-23,24,25,26,27-13C5?can be used as a stable isotope internal standard for data interpretation in specific biological samples by mass spectrometry.
2. A metabolite of Vitamin D. The principal circulating form of vitamin D3, formed in the liver by hydroxylation at C-25. Calcium regulator.
3. This product may be used as an analytical standard.
Definition
ChEBI: A hydroxycalciol that is calciol in which the hydrogen at position 25 has been replaced by a hydroxy group. A prehormone resulting from the oxidation of calciol in the liver, it is further hydroxylated in the kidney to give calcitriol, the active form of v
tamin D3.
Manufacturing Process
A solution of 125 mg of cholesta-5,7-diene-3β,25-diol in 125 ml of benzene
and 10 ml of absolute ethanol is placed in a photo reactor equipped with a
quartz lamp well cooled with water and a nitrogen inlet. The reaction mixture
is cooled to about 16°C, and purged with N2. A Hanovia 8A36, 100-watt lamp,
centered in the lampwell 2.5 cm from the internal surface of the reaction
mixture, is turned on for 15 minutes, including the 5-6 minutes required for
the lamp to reach full brilliance. The lamp is a typical actinic energy source
suitable for the irradiation step in the known synthesis of Vitamin D, and can
be replaced by any such available lamp. The specific lamp used is a 100-watt
high-pressure quartz mercury-vapor lamp, producing approximately 11.5
watts total radiated energy distributed over the range of 220-1400 nm. A fast
stream of water is necessary to keep the outlet water temperature below
20°C. The reaction mixture is concentrated to dryness in a rotary evaporator
below room temperature. The semisolid residue is triturated with 5 ml of 35%
ethyl acetate-65% Skellysolve B hexanes mixture and filtered and another 5
ml of the same solvent is used for wash. The solid contains unreacted starting
material and the liquor contains the product. The liquor is poured onto a 40 g
column containing TLC grade Florisil, 150-200 mesh packed wet with 35%
ethyl acetate-Skellysolve B hexanes, and the products are eluted with the
same solvent mixture collecting 10 ml fractions. The fractions containing the
product, located by spotting on a TLC plate, are combined and evaporated to
dryness below room temperature to give an oily residue. A few drops of
absolute ether are added and removed under vacuum to give 25-
hydroxyprecholecalciferol as a fluffy foam; yield 60 mg.A solution of about 300 mg of 25-hydroxyprecholecalciferol prepared as
described above in 5 ml of chloroform is heated for 3.5 hours at 70°-75°C
under N2 in a sealed flask. The solvent is evaporated and the residue is
chromatographed through a 60 g column containing TLC grade Florisil, 150-
200 mesh packed wet with 35% ethyl acetate in Skellysolve B hexanes. The
column is eluted with the same solvent mixture, collecting 10 ml fractions.
The fractions which crystallize on trituration with aqueous methanol are
combined and recrystallized twice from aqueous methanol to give 25-
hydroxycholecalciferol hydrate; yield 120 mg, MP 81°-83°C (sinters 75°C).A solution of 20 mg of 25-hydroxycholecalciferol hydrate, prepared as
described above, in 20 ml of methylene chloride is dried with 200 mg of
anhydrous sodium sulfate. The solution is filtered and the filtrate is
evaporated to yield 25-hydroxycholecalciferol essentially anhydrous as an
amorphous oil.
Brand name
Calderol (Organon).
Therapeutic Function
Calcium regulator
General Description
25-Hydroxyvitamin D3 (calcifediol) is a prohormone produced via hydroxylation of vitamin D3 (cholecalciferol) in the liver. It is a precursor for the synthesis of calcitriol {1,25-dihydroxyvitamin D3 or [1,25(OH)2D3]}. It is used as a biomarker to determine the status of vitamin D in the body.25-Hydroxyvitamin D3-23,24,25,26,27-13C5?is an isotope of vitamin D3 wherein C-23, C-24, C-25, C-26, C-27 carbons are replaced by 13C6 isotope.
Biochem/physiol Actions
Ergocalciferol (vitamin D2) and 25-Hydroxycholecalciferol (vitamin D3) are the two form of vitamin D which are activated in vivo by hydroxylation. Vitamin D2 and D3 may be used in a wide range of studies to assess their effects on function such as immune function and calcium homeostasis.
Check Digit Verification of cas no
The CAS Registry Mumber 19356-17-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,9,3,5 and 6 respectively; the second part has 2 digits, 1 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 19356-17:
(7*1)+(6*9)+(5*3)+(4*5)+(3*6)+(2*1)+(1*7)=123
123 % 10 = 3
So 19356-17-3 is a valid CAS Registry Number.
InChI:InChI=1/C27H44O2.H2O/c1-19-10-13-23(28)18-22(19)12-11-21-9-7-17-27(5)24(14-15-25(21)27)20(2)8-6-16-26(3,4)29;/h11-12,20,23-25,28-29H,1,6-10,13-18H2,2-5H3;1H2/b21-11+,22-12-;/t20-,23+,24-,25+,27-;/m1./s1
19356-17-3Relevant articles and documents
Optimization of bioconversion conditions for vitamin D3 to 25-hydroxyvitamin D using Pseudonocardia autotrophica CGMCC5098
Luo, Jinqi,Jiang, Fang,Fang, Weizhen,Lu, Qun
, p. 11 - 18 (2017)
The optimal culture conditions for bioconversion of vitamin D3 to calcifediol (25(OH)D3) were investigated by varying carbon and nitrogen sources, metal salt concentrations, initial pH, temperature, solvents, surfactants, and agitation speed. In the process of this microbial hydroxylation, the timing of the addition of vitamin D3, which is dissolved in ethanol, is of critical importance. Besides, the concentration of ethanol in zymotic fluid is the key factor to get high conversion ratio of vitamin D3. In particular, the optimal culture conditions were 1.5% glucose, 1.5% soybean cake meal, 0.5% yeast extract, 0.5% corn steep liquor, 0.3% CaCO3, 0.1% NaCl, 0.2% KH2PO4, pH 7.2 at 27 °C and the timing of the addition of vitamin D3 dissolved in 5% (v/v) ethanol was 48 h followed by the inoculation of seed culture broth. Under the optimized conditions, the conversion of vitamin D3 (1 g/L) by Pseudonocardia autotrophica CGMCC5098 in 50 L fermenter resulted in about 61.31% bioconversion ratio (639 mg/L) of 25(OH)D3 on the 5th day.
Isolation and identification of 2α,25-dihydroxyvitamin D3, a new metabolite from Pseudonocardia autotrophica 100U-19 cells incubated with Vitamin D3
Takeda, Koji,Kominato, Kaichiro,Sugita, Atsuko,Iwasaki, Yukiko,Shimazaki, Mika,Shimizu, Masato
, p. 736 - 744 (2006)
Pseudonocardia autotrophica converted Vitamin D3 to 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3. The hydroxylation of Vitamin D3 with P. autotrophica was enhanced by the addition of cyclodextrin. In this microbial hydroxylation, a new Vitamin D3 metabolite was observed in the reaction mixture of P. autotrophica and Vitamin D3, and was isolated in a pure form by several steps of chromatography. The structure of the new metabolite was determined to be 2α,25-dihydroxyvitamin D3 by UV, NMR and mass spectroscopic analyses. Biological evaluation of the new metabolite was conducted by means of several experiments.
25-HydroxyvitaminD3 Synthesis by Enzymatic Steroid Side-Chain Hydroxylation with Water
Warnke, Markus,Jung, Tobias,Dermer, Juri,Hipp, Karin,Jehmlich, Nico,Von Bergen, Martin,Ferlaino, Sascha,Fries, Alexander,Müller, Michael,Boll, Matthias
, p. 1881 - 1884 (2016)
The hydroxylation of vitaminD3 (VD3, cholecalciferol) side chains to give 25-hydroxyvitaminD3 (25OHVD3) is a crucial reaction in the formation of the circulating and biologically active forms of VD3. It is usually catalyzed by cytochrome P450 monooxygenases that depend on complex electron donor systems. Cell-free extracts and a purified Mo enzyme from a bacterium anaerobically grown with cholesterol were employed for the regioselective, ferricyanide-dependent hydroxylation of VD3 and proVD3 (7-dehydrocholesterol) into the corresponding tertiary alcohols with greater than 99 % yield. Hydroxylation of VD3 strictly depends on a cyclodextrin-assisted isomerization of VD3 into preVD3, the actual enzymatic substrate. This facile and robust method developed for 25OHVD3 synthesis is a novel example for the concept of substrate-engineered catalysis and offers an attractive alternative to chemical or O2 /electron-donor-dependent enzymatic procedures.
Functional interactions of adrenodoxin with several human mitochondrial cytochrome P450 enzymes
Barckhausen, Ian R.,Child, Stella A.,Glass, Sarah M.,Goldfarb, Margo H.,Guengerich, F. Peter,Reddish, Michael J.
, (2020)
Seven of the 57 human cytochrome P450 (P450) enzymes are mitochondrial and carry out important reactions with steroids and vitamins A and D. These seven P450s utilize an electron transport chain that includes NADPH, NADPH-adrenodoxin reductase (AdR), and adrenodoxin (Adx) instead of the diflavin NADPH-P450 reductase (POR) used by the other P450s in the endoplasmic reticulum. Although numerous studies have been published involving mitochondrial P450 systems, the experimental conditions vary considerably. We compared human Adx and bovine Adx, a commonly used component, and found very similar catalytic activities in reactions catalyzed by human P450s 11B2, 27A1, and 27C1. Binding constants of 6–200 nM were estimated for Adx binding to these P450s using microscale thermophoresis. All P450 catalytic reactions were saturated at 10 μM Adx, and higher concentrations were not inhibitory up to at least 50 μM. Collectively these studies demonstrate the tight binding of Adx (both human and bovine) to AdR and to several mitochondrial P450s and provide guidance for optimization of Adx-dependent P450 reactions.
Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases
Aiba, Isamu,Yamasaki, Tomoaki,Shinki, Toshimasa,Izumi, Shunsuke,Yamamoto, Keiko,Yamada, Sachiko,Terato, Hiroaki,Ide, Hiroshi,Ohyama, Yoshihiko
, p. 849 - 856 (2006)
vitamin D is 25-hydroxylated in the liver, before being activated by 1α-hydroxylation in the kidney. Recently, the rat cytochrome P450 2J3 (CYP2J3) has been identified as a principal vitamin D 25-hydroxylase in the rat [Yamasaki T, Izumi S, Ide H, Ohyama Y. Identification of a novel rat microsomal vitamin D3 25-hydroxylase. J Biol Chem 2004;279(22):22848-56]. In this study, we examine whether human CYP2J2 that exhibits 73% amino acid homology to rat CYP2J3 has similar catalytic properties. Recombinant human CYP2J2 was overexpressed in Escherichia coli, purified, and assayed for vitamin D 25-hydroxylation activity. We found significant 25-hydroxylation activity toward vitamin D3 (turnover number, 0.087 min-1), vitamin D2 (0.16 min-1), and 1α-hydroxyvitamin D3 (2.2 min-1). Interestingly, human CYP2J2 hydroxylated vitamin D2, an exogenous vitamin D, at a higher rate than it did vitamin D3, an endogenous vitamin D, whereas, rat CYP2J3 hydroxylated vitamin D3 (1.4 min-1) more efficiently than vitamin D2 (0.86 min-1). Our study demonstrated that human CYP2J2 exhibits 25-hydroxylation activity as well as rat CYP2J3, although the activity of human CYP2J2 is weaker than rat CYP2J3. CYP2J2 and CYP2J3 exhibit distinct preferences toward vitamin D3 and D2.
Preparation method of 25-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3 and isotope internal standard compound thereof
-
Paragraph 0065-0066; 0074-0077, (2020/08/27)
The invention discloses a preparation method of 25-hydroxyvitamin D3 and 1alpha, 25-dihydroxyvitamin D3 and an isotope internal standard compound thereof. The preparation method comprises the following steps: a compound III is subjected to SO2 conjugate protection, O3 oxidation, NaBH4 reduction, iodination ring opening, conjugate addition with acrylate, and reaction with a methyl Grignard reagentor isotope labeled methyl Grignard reagent, a silicon protecting group is removed under the action of TBAF, and a product is obtained through ultraviolet irradiation configuration inversion under thecatalysis of 9-acetyl anthracene. The method is good in reaction selectivity, high in total yield, simple and convenient to operate and short in isotope introduction step, and the isotope utilizationrate is greatly increased.
