32222-06-3 Usage
Description
Calcitriol, also known as 1,25-dihydroxyvitamin D3, is the biologically active form of vitamin D3 and a steroid hormone with three hydroxyl groups. It is the most effective form of vitamin D, playing a crucial role in regulating calcium and phosphorus concentrations in the body. Calcitriol is synthesized from 7-dehydrocholesterol in humans through a non-enzymatic photochemical reaction with UV light in the skin, followed by hydroxylation in the liver and kidney. It is involved in various physiological processes, including increasing calcium absorption in the intestine, stimulating osteoblasts for bone mineralization, and regulating bone growth.
Uses
Used in Pharmaceutical Industry:
Calcitriol is used as a calcium regulator for treating and preventing low levels of calcium and bone disease in patients with impaired kidney or parathyroid gland function. It is particularly effective in managing conditions such as hypocalcemia, hypoparathyroidism, osteomalacia, rickets, chronic kidney disease, renal osteodystrophy, and osteoporosis.
Used in Vitamin Medicines:
Calcitriol serves as an essential component in vitamin medicines, specifically for addressing renal bone malnutrition in patients with chronic renal failure.
Used in Oncology:
Calcitriol exhibits antineoplastic properties, making it a potential chemopreventive agent for colon and prostate cancers. It induces cell cycle arrest, cell differentiation, and apoptosis, contributing to the inhibition of tumor growth and progression.
Used in Dermatology:
As an anti-psoriatic agent, Calcitriol is utilized in the treatment of psoriasis, a chronic skin condition characterized by the rapid buildup of skin cells.
Calcitriol is available under various brand names, including Calcijex (Abbott) and Rocaltrol (Roche), and is typically presented as a white crystalline powder. Its production involves a tightly regulated process, starting with the conversion of 7-dehydrocholesterol to cholecalciferol in the skin, followed by hydroxylation in the liver to form calcidiol, and finally, oxidation in the kidney to produce calcitriol.
References
https://pubchem.ncbi.nlm.nih.gov
https://medlineplus.gov
http://flexikon.doccheck.com/en/Calcitriol
https://en.wikipedia.org/wiki/Calcitriol
https://www.webmd.com
Originator
Rocaltrol,Roche,US,1978
Manufacturing Process
1α,25-Dihydroxyprecholecalciferol: A solution of 1α,25-
diacetoxyprecholecalciferol (0.712 g, 1.42 mmols), potassium hydroxide (2.0
g, 35.6 mmols) and methanol (40 ml) was stirred at room temperature under
argon for 30 hours. The reaction mixture was concentrated under reduced
pressure. Water (50 ml) was added to the residue and the mixture was
extracted with methylene chloride (3 x 100 ml). The combined organic
extracts were washed with saturated sodium chloride solution (3 x 50 ml),
dried over anhydrous sodium sulfate, filtered and evaporated under reduced
pressure to give 0.619 g of 1alpha,25-dihydroxyprecholecalciferol as a thick
oil.1α,25-Dihydroxycholecalciferol: A solution of 1α,25-dihydroxyprecholecalciferol
[0.619 g in dioxane (30 ml)] was heated under reflux for 30 minutes under an
atmosphere of argon. The reaction mixture was concentrated under reduced pressure and the residue was purified with a Waters Associates liquid
chromatograph model 202 using a 8 foot * 3/8 inch Porasil A column and a
5:1 mixture of ethyl acetate-n-hexane as the eluent to give 0.474 g (80%
yield based on 1α,25-diacetoxyprecholecalciferol) of pure 1α,25-
dihydroxycholecalciferol. Recrystallization from methyl formate afforded 0.340
g of 1α,25-dihydroxcholecalciferol as colorless crystals, MP 113°-114°C.
Therapeutic Function
Calcium regulator
Biological Activity
Active metabolite of vitamin D 3 that activates the vitamin D receptor (VDR). Displays calcemic actions; stimulates intestinal and renal Ca 2+ absorption and regulates bone Ca 2+ turnover. Exhibits antitumor activity; inhibits in vivo and in vitro cell proliferation in a wide range of cells including breast, prostate, colon, skin and brain carcinomas and myeloid leukemia cells.
Biochem/physiol Actions
Biologically active form of vitamin D3 in calcium absorption and deposition. 1α,25-Dihydroxyvitamin D3 has widespread effects on cellular differentiation and proliferation, and can modulate immune responsiveness, and central nervous system function. Recent studies suggest that 1α,25-dihydroxyvitamin D3 acts as a chemopreventive agent against several malignancies including cancers of the prostate and colon and shows synergy with other anticancer compounds.
Clinical Use
Vitamin D analogue:
Promotes intestinal calcium absorption
Suppresses PTH production and release
Veterinary Drugs and Treatments
Calcitriol may be potentially beneficial in the adjunctive treatment
of chronic renal
disease in dogs and cats but its use is somewhat
controversial, particularly the decision on how soon in the course
of chronic renal insufficiency it should employed. It may also be of
benefit in treating some types of dermatopathies (primary idiopathic
seborrhea).
Drug interactions
Potentially hazardous interactions with other drugs
Antiepileptics: the effects of vitamin D may
be reduced in patients taking barbiturates or
anticonvulsants.
Diuretics: increased risk of hypercalcaemia with
thiazides.
Sevelamer: absorption may be impaired by sevelamer
Metabolism
During transport in the blood at physiological
concentrations, calcitriol is mostly bound to a specific
vitamin D binding protein (DBP), but also, to a lesser
degree, to lipoproteins and albumin. At higher blood
calcitriol concentrations, DBP appears to become
saturated, and increased binding to lipoproteins and
albumin occurs.
Calcitriol is inactivated in both the kidney and
the intestine, through the formation of a number
of intermediates including the formation of the
1,24,25-trihydroxy derivatives. It is excreted in the bile
and faeces and is subject to enterohepatic circulation.
Check Digit Verification of cas no
The CAS Registry Mumber 32222-06-3 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,2,2,2 and 2 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 32222-06:
(7*3)+(6*2)+(5*2)+(4*2)+(3*2)+(2*0)+(1*6)=63
63 % 10 = 3
So 32222-06-3 is a valid CAS Registry Number.
InChI:InChI=1/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24?,25+,27-/m1/s1
32222-06-3Relevant articles and documents
Synthesis of β-D-glucopyranosides of some hydroxylated vitamin-D compounds
Furst,Labler,Meier
, p. 2093 - 2102 (1983)
-
Preparation method of 25-hydroxyvitamin D3, 1alpha, 25-dihydroxyvitamin D3 and isotope internal standard compound thereof
-
Paragraph 0102-0103; 0111-0114, (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.
A single mutation at the ferredoxin binding site of P450 Vdh enables efficient biocatalytic production of 25-hydroxyvitamin D3
Yasutake, Yoshiaki,Nishioka, Taiki,Imoto, Noriko,Tamura, Tomohiro
, p. 2284 - 2291 (2013/12/04)
Vitamin D3 hydroxylase (Vdh) from Pseudonocardia autotrophica is a cytochrome P450 monooxygenase that catalyzes the two-step hydroxylation of vitamin D3 (VD3) to produce 25-hydroxyvitamin D 3 (25(OH)VD3) and 1α,25-dihydroxyvitamin D 3 (1α,25(OH)2VD3). These hydroxylated forms of VD3 are useful as pharmaceuticals for the treatment of conditions associated with VD3 deficiency and VD3 metabolic disorder. Herein, we describe the creation of a highly active T107A mutant of Vdh by engineering the putative ferredoxin-binding site. Crystallographic and kinetic analyses indicate that the T107A mutation results in conformational change from an open to a closed state, thereby increasing the binding affinity with ferredoxin. We also report the efficient biocatalytic synthesis of 25(OH)VD3, a promising intermediate for the synthesis of various hydroxylated VD3 derivatives, by using nisin-treated Rhodococcus erythropolis cells containing VdhT107A. The gene-expression cassette encoding Bacillus megaterium glucose dehydrogenase-IV was inserted into the R. erythropolis chromosome and expressed to avoid exhaustion of NADH in a cytoplasm during bioconversion. As a result, approximately 573 μg mL-1 25(OH)VD3 was successfully produced by a 2 h bioconversion. Copyright
