50-23-7 Usage
Chemical Properties
crystalline white powder
Originator
Hydrocortone,MSD,US,1952
Uses
Different sources of media describe the Uses of 50-23-7 differently. You can refer to the following data:
1. Principle glucocorticoid hormone produced by adrenal cortex. An anti-inflammatory hormone.
2. glucocorticoid, antiinflammatory
3. Cortisol, or Hydrocortisone, is a steroid hormone, more specifically a glucocorticoid, produced by the zona fasciculata of the adrenal gland. Cortisol is released in response to stress and a low level
of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat, protein and carbohydrate metabolism.
Definition
ChEBI: A C21-steroid that is pregn-4-ene substituted by oxo groups at positions 3 and 20 and hydroxy groups at positions 11, 17 and 21. Cortisol is a corticosteroid hormone or glucocorticoid produced by zona fasciculata of the adrenal cortex,
which is a part of the adrenal gland. It is usually referred to as the "stress hormone" as it is involved in response to stress and anxiety, controlled by corticotropin-releasing hormone (CRH). It increases blood pressure and blood sugar, and reduces immun
responses
Indications
Hydrocortisone (Cortizone, Cortaid, Anusol-HC, Hytone, LactiCare-HC, Sarnol
HC, Penecort, Texacort, and many other branded products) may be purchased as a
generic drug.
Manufacturing Process
The following example from US Patent 2,602,769 illustrates the preparation of
17-hydroxycorticosterone (compound F) from 11-desoxy-17-
hydroxycorticosterone (compound S). A medium was prepared from 0.5%
peptone, 2% dextrose, 0.5% soybean meal, 0.5% KH2PO4, 0.5% sodium
chloride and 0.3% yeast extract in tap water. To 200 ml of this sterilized
medium was added an inoculum of the vegetative mycella of Cunninghamella blakesleeana. The spores had first been transferred from a sport slant to a
broth medium and the broth medium was aerobically incubated at 24°C for 24
to 72 hours in a .reciprocating shaker until the development of vegetative
growth. The inoculated medium containing added vegetative mycella of
Cunninghamella blakesleeana was incubated for 48 hours at 24°C following
which was added 66 mg of compound S, 11-desoxy-17-hydroxycorticosterone
in solution in a minimum of ethanol, and incubation was maintained for 7
hours at 24°C. The beer containing steroid was diluted with 800 ml of
acetone, shaken 1 hour on a reciprocating shaker and filtered. The cake was
suspended in 500 ml of acetone, shaken another hour and again filtered. The
filtrates were combined and the acetone was volatilized under reduced
pressure at 50°C. Acetone was then added, if necessary, to bring the
concentration to 20% acetone and this resulting aqueous acetone solution was
extracted five times each with one-third volume of Skellysolve B petroleum
ether to remove fatty materials. These extracts were back washed two times
with one-tenth volume of 20% aqueous acetone and the washings were added
to the main acetone extract.
The combined acetone extracts were extracted six times with one-fourth
volume of ethylene dichloride and the ethylene dichloride extract was
evaporated under vacuum to leave the steroid residue. This steroid residue
was taken up in a minimum of methylene chloride and applied to the top of a
column packed with 30 grams of silica which had been previously triturated
with 21 ml of ethylene glycol. Then various developing mixtures, saturated
with ethylene glycol, were passed over the column. Cuts were made as each
steroid was eluted as determined by the lowering of the absorption of light at
240 nm on the automatic chromatographic fraction cutter.
Band Solvent Tube No. (60ml) Crude Solids (mg)
1 Cyclohexane 1-4 11
2 Cyclohexane-methylene chloride 3:1 5-13 6.4 compound S
3 Cyclohexane-methylene chloride 1:1 14-16 3.0
4 Cyclohexane-methylene chloride 2:3 17-23 6.0 compound E
5 Cyclohexane-methylene chloride 1:4 24-38 12.2 compound F
6 Methylene chloride 39-59 4.8
A 7.7 mg portion of band 5 was taken up in a minimum of acetone and
refrigerated until crystals separated. This cold acetone mixture was
centrifuged and the supernatant liquid removed by pipette. To the remaining
crystals, a few drops of ice-cold ether-acetone, three to one mixture, were
added, shaken, recentrifuged and the supernatant wash liquid removed by
pipette. The ether-acetone wash was repeated. The resulting crystals were
dried under vacuum yielding 3.3 mg of pure compound F, 17-
hydroxycorticosterone.
Brand name
Acticort (Baker Norton); Ala-Cort (Del
Ray); Cetacort (Healthpoint); Colocort (Paddock); Cort-
Dome (Bayer); Cortef (Pharmacia & Upjohn); Cortenema
(Solvay Pharmaceuticals); Cortril (Pfizer); Dermacort
(Monarch); Dermacort (Solvay Pharmaceuticals); Eldecort
(Valeant); Epicort (Bluline); Flexicort (Westwood-
Squibb); Glycort (Heran); Hi-Cor (C & M); Hydro-Rx (X
Gen); Hydrocortone (Merck); Hytone (Dermik); Hytone
(Sanofi Aventis); Nutracort (Healthpoint); Penecort (Allergan);
Proctocort (Monarch); Stie-Cort (Stiefel); Synacort
(Medicis); Texacort (Sirius).
Therapeutic Function
Glucocorticoid
General Description
Hydrocortisone, 11β,17,21-trihydroxypregn-4-ene-3,20-dione, is the primary natural GCin humans. Despite the large number of synthetic GCs, hydrocortisone,its esters, and its salts remain a mainstay ofmodern adrenocortical steroid therapy and the standard forcomparison of all other GCs and MCs . It isused for all the indications mentioned previously.
Health Hazard
Cortisol Increases (1) protein catabolism (excepting liver) gluconeogenesis; (2) carbohydrate anabolism (liver); (3) blood sugar; (4) glucose absorption; (5) brain excitation; (6) spread of infections; (7)urinary glucose and nitrogen; (8) stress tolerance; (9) lactation; (10) water diuresis.Regulates general adaptation syndrome, water balance, blood pressure, and hormone release.Decreases (1) fat anabolism; (2) growth rate; (3) inflammation; (4) eosinophils; (5) lymphocytes; (6) antigen sensitivity; (7) respiratory quotient; (8) ketosis; (9) wound healing; (10) skin pigmentation; (11)RBC hemolysis.
Biological Activity
hydrocortisone is a main glucocorticoid secreted by the adrenal cortex.
Biochem/physiol Actions
Product does not compete with ATP.
Contact allergens
Hydrocortisone is the principal glucocorticoid hor-
mone produced by the adrenal cortex and is used topi-
cally or systemically. It belongs to the allergenic A
group. Marker of allergy is tixocortol pivalate.
Mechanism of action
Hydrocortisone exhibits anti-shock, anti-allergy, and anti-inflammatory action. It raises
sugar content in the blood, increases potassium secretion, and lowers sodium excretion
from the body. It exhibits anti-metabolic action and reduces histamine synthesis in the
body.
Clinical Use
Hydrocortisone is endogenous, and it has both glucocorticoid and mineralocorticoid activity. It is
the fundamental structure by which the glucocorticoid and mineralocorticoid activities of all other
corticosteroids are judged. Functional groups that are essential for both mineralocorticoid and
glucocorticoid activity include the pregnane skeleton with an all-trans backbone, the ring
A-en-one system (?4
-3-one ring A) and the 17β-ketol side chain (C-20-keto-C-21-hydroxy). The
glucocorticoid activity is enhanced by the C-11 and C-17 hydroxyl groups. Hydrocortisone can be
used to treat severe asthmatic attacks that do not respond to conventional treatment. It is
available as various ester forms.
Safety Profile
Poison by
Synthesis
Hydrocortisone, 11β,17α,21-trihydroxypregn-4-en-3,20-dione
(27.1.8), is synthesized in various ways and from various compounds containing a
steroid skeleton. According to one of them, hydrocortisone is synthesized from dextropregnenolone.
The double bond between C16 and C17 of dextropregnenolone is oxidized
using hydrogen peroxide in a base, forming an epoxide 27.1.1. Interacting this with
hydrobromic acid opens the epoxide ring, forming 16-bromo-17-hydroxydextropregnenolone
(27.1.2). The resulting bromo derivative undergoes debromination by hydrogen
using a palladium on carbon catalyst, and then the secondary hydroxyl group
undergoes esterification using formic acid in the presence of p-toluenesulfonic acid, giving
3-formyloxy-17-hydroxydextropregnenolone (27.1.3). The resulting 3-formyloxy-
17-hydroxydextropregnenolone undergoes bromination by bromine, which results in
bromination of the C4–C5 double bond and the methyl group of acetyl moiety, which
forms a tribromo derivative 27.1.4. Reacting the product with sodium iodide results in
dehalogenation of the resulting vicinal dibromide, during which the double bond is
simultaneously shifted into the position between carbon atoms C5 and C6 that gives the
bromoketone 27.1.5. This is reacted with potassium acetate and then with acetic anhydride
in the presence of p-toluenesulfonic acid, forming a diacetate 27.1.6. Taking into
account that unlike acetates, formates are easily oxidized and give exactly the same
products as do the corresponding alcohols, the resulting diacetate is oxidized in an
Oppenauer oxidation reaction, using aluminum isopropoxide and cyclohexanone as a
hydrogen acceptor. During this, isomerization of the double bond into the primary position
between C4 and C5 simultaneously takes place, forming a stable, conjugated
vinylketone, after which the acetyl protection of both hydroxyl groups is hydrolyzed
using potassium hydroxide, giving 17-hydroxy-11-deoxycorticosterone (27.1.7). This
undergoes microbiological oxidation at position C1, forming the desired hydrocortisone
(27.1.8). Side reactions of microbiological oxidation using the very same microorganisms
can cause hydroxylation of steroids in different positions, using easily accessible
progesterone as an initial substance.
Veterinary Drugs and Treatments
Because of its rapid effect and relatively high mineralocorticoid effect,
hydrocortisone sodium succinate (Solu-Cortef?) is the most
commonly used form of this medication when an acute glucocorticoid/
mineralocorticoid effect is desired (e.g., acute adrenal insufficiency).
Corticosteroids have not been shown beneficial in treating
hypovolemic shock, but low dose glucocorticoids probably reduce
mortality associated with septic shock.
Glucocorticoids have been used in an attempt to treat practically
every malady that afflicts man or animal, but there are three broad
uses and dosage ranges for use of these agents. 1) Replacement of
glucocorticoid activity in patients with adrenal insufficiency, 2)
as an antiinflammatory agent, and 3) as an immunosuppressive.
Among some of the uses for glucocorticoids include treatment of:
endocrine conditions (e.g., adrenal insufficiency), rheumatic diseases
(e.g., rheumatoid arthritis), collagen diseases (e.g., systemic
lupus), allergic states, respiratory diseases (e.g., asthma), dermatologic
diseases (e.g., pemphigus, allergic dermatoses), hematologic
disorders (e.g., thrombocytopenias, autoimmune hemolytic anemias),
neoplasias, nervous system disorders (increased CSF pressure),
GI diseases (e.g., ulcerative colitis exacerbations), and renal
diseases (e.g., nephrotic syndrome). Some glucocorticoids are used
topically in the eye and skin for various conditions or are injected
intra-articularly or intra-lesionally. The above listing is certainly
not complete.
Purification Methods
Recrystallise hydrocortisone from EtOH or isoPrOH. It is bitter tasting and has UV with max at 242 nm (log 4.20). Its solubility at 25o is: H2O (0.28%), EtOH (1.5%), MeOH (0.62%), Me2CO (0.93%), CHCl3 (0.16%), propylene glycol (1.3%) and Et2O (0.35%). It gives an intense green colour with conc H2SO4. [Wendler et al. J Am Chem Soc 72 5793 1950, Beilstein 8 IV 3422.]
Check Digit Verification of cas no
The CAS Registry Mumber 50-23-7 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 50-23:
(4*5)+(3*0)+(2*2)+(1*3)=27
27 % 10 = 7
So 50-23-7 is a valid CAS Registry Number.
InChI:InChI=1/C21H30O5/c1-19-7-5-13(23)9-12(19)3-4-14-15-6-8-21(26,17(25)11-22)20(15,2)10-16(24)18(14)19/h9,14-16,18,22,24,26H,3-8,10-11H2,1-2H3/t14-,15+,16+,18+,19+,20-,21+/m1/s1
50-23-7Relevant articles and documents
Evidence for a new biologic pathway of androstenedione synthesis from 11-deoxycortisol
Auzeby, Andre,Bogdan, Andre,Touitou, Yvan
, p. 33 - 36 (1991)
17-Hydroxyprogesterone is a well-known precursor of androstenedione in adrenal biosynthesis.This study using sheep adrenal incubations demonstrates that 11-deoxycortisol, the precursor of cortisol synthesis, also can be a precursor of androstenedione.Indeed, our data shown that androstenedione synthesis is negatively correlated to the synthesis of cortisol and cortisone.This fact allowed us to infer that this new pathway is closely related to the activity of the 11β-hydroxylase that is responsible for the synthesis of cortisol.Indeed, when the activity of this enzyme is impaired, 11-deoxycortisol follows the pathway that leads to androstenedione synthesis in the adrenals.This pathway could explain, at least in part, the marked increase of androstenedione observed in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.
ADRENAL 11-HYDROXYLASE ACTIVITY IN A HYPERCORTISOLEMIC NEW WORLD PRIMATE: ADAPTIVE INTRA-ADRENAL CHANGES
Albertson, Barry D.,Brandon, David D.,Chrousos, George P.,Loriaux, D. Lynn
, p. 497 - 506 (1987)
The squirrel monkey, a representative New World primate, has high plasma cortisol and aldosterone concentrations when compared to Old World primates.We measured adrenal mitochondrial 11-hydroxylase (11-OHase) activity in squirrel monkeys and in two representative Old World species (cynomolgus and rhesus macaques) in an effort to explain these elevated plasma glucocorticoid and mineralocorticoid levels.The activity of 11-OHase was 5-fold higher in the squirrel monkey than in the Old World species tested.Calculated 11-OHase Vmax was different in the squirrel monkey and the cynomolgus.However, the Km values were similar in the New World primate when compared to cynomolgus.The ability of metyrapone to block 11-OHase was less in the former than in the latter.The data are consistent with the hypothesis that the squirrel monkey adrenal cortex possesses an increased number of 11-hydroxylase enzyme units compared to that of Old World primate species, and is therefore more efficient in producing cortisol.This difference in 11-OHase activity in the squirrel monkey, in addition to other previously reported adrenal steroidogenic enzyme alterations, may be adaptive in nature, favoring increased cortisol and aldosterone production in this and possibly other New World primate species.
Hydrocortisone compound with 1/10 water
-
Paragraph 0035; 0037-0038; 0039; 0041-0042; 0043; 0045-0046, (2020/01/14)
The invention discloses a hydrocortisone compound with 1/10 water and a preparation method of the hydrocortisone compound. According to powder X-ray diffraction measurement of the compound, characteristic diffraction peaks are shown at positions with 2theta+/-0.2 degree diffraction angles of 5.6 degrees, 14.1 degrees, 16.0 degrees, 17.2 degrees and 18.5 degrees. The prepared hydrocortisone compound with 1/10 water has the advantages of good photostability and high purity, and the preparation method is simple in process, high in yield and high in repeatability, and is suitable for industrial production.
Preparation method of high-purity hydrocortisone
-
Paragraph 0026; 0029; 0030; 0033; 0034; 0037, (2020/08/30)
The invention discloses a preparation method of high-purity hydrocortisone, and belongs to the technical field of preparation and processing of medicines. According to the method, 17alpha-hydroxypregna-4, 9 (11)-diene-3, 20-diketone-21-acetate is used as a starting material, and the high-purity hydrocortisone is prepared through three steps of bromo-hydroxyl, debromination and hydrolysis. According to the preparation method of the high-purity hydrocortisone disclosed by the invention, the reaction process can be effectively shortened by improving the defects of a traditional process, the generation of impurities during the reaction process is controlled, the use of iodine with characteristics of high toxicity and environmental unfriendliness is avoided, the environmental pollution is reduced, and the method has characteristics of high overall conversion rate, simple operation and wide market prospect, and is suitable for industrial production.
Dehalogenation methodof 9-halogenated steroid compound and application
-
Paragraph 0161-0163, (2021/01/11)
The invention provides a dehalogenation method of a 9-halogenated steroid compound and application, and relates to the technical field of chemical synthesis. The dehalogenation method of the 9-halogenated steroid compound comprises the following steps: reacting a compound I with a hydrogen donor and an azo radical initiator to obtain a 9-dehalogenated product compound II of the 9-halogenated steroid compound. According to the dehalogenation method of the 9-halogenated steroid compound, a hydrogen donor adopts one or a combination of more of hypophosphorous acid and hypophosphite, formic acid and formate, organic silicon hydride, hydrazine compounds or cyclohexene, and an initiator adopts an azo free radical initiator. Reagents such as chromium, divalent chromium salt, trivalent chromium salt or tributyltin hydride which are high in toxicity and cause serious pollution to the environment are not used in the reaction, the method is green and environmentally friendly, the synthesis process is simple, convenient and easy to implement, and the production applicability is improved.
A biocatalytic hydroxylation-enabled unified approach to C19-hydroxylated steroids
Wang, Junlin,Zhang, Yanan,Liu, Huanhuan,Shang, Yong,Zhou, Linjun,Wei, Penglin,Yin, Wen-Bing,Deng, Zixin,Qu, Xudong,Zhou, Qianghui
, (2019/08/02)
Steroidal C19-hydroxylation is pivotal to the synthesis of naturally occurring bioactive C19-OH steroids and 19-norsteroidal pharmaceuticals. However, realizing this transformation is proved to be challenging through either chemical or biological synthesis. Herein, we report a highly efficient method to synthesize 19-OH-cortexolone in 80% efficiency at the multi-gram scale. The obtained C19-OH-cortexolone can be readily transformed to various synthetically useful intermediates including the industrially valuable 19-OH-androstenedione, which can serve as a basis for synthesis of C19-functionalized steroids as well as 19-nor steroidal drugs. Using this biocatalytic C19-hydroxylation method, the unified synthesis of six C19-hydroxylated pregnanes is achieved in just 4 to 9 steps. In addition, the structure of sclerosteroid B is revised on the basis of our synthesis.
(Poly)cationic λ3-Iodane-Mediated Oxidative Ring Expansion of Secondary Alcohols
Walters, Jennifer C.,Tierno, Anthony F.,Dubin, Aimee H.,Wengryniuk, Sarah E.
supporting information, p. 1460 - 1464 (2018/04/06)
Herein, a simplified approach to the synthesis of medium-ring ethers through the electrophilic activation of secondary alcohols with (poly)cationic λ3-iodanes (N-HVIs) is reported. Excellent levels of selectivity are achieved for C–O bond migration over established α-elimination pathways, enabled by the unique reactivity of a novel 2-OMe-pyridine-ligated N-HVI. The resulting hexafluoroisopropanol (HFIP) acetals are readily derivatized with a range of nucleophiles, providing a versatile functional handle for subsequent manipulations. The utility of this methodology for late-stage natural product derivatization was also demonstrated, providing a new tool for diversity-oriented synthesis and complexity-to-diversity (CTD) efforts. Preliminary mechanistic investigations reveal a strong effect of alcohol conformation on the reactive pathway, thus providing a predictive power in the application of this approach to complex molecule synthesis.
Preparation method of hydrocortisone
-
Paragraph 0059; 0060, (2018/09/21)
The invention relates to a preparation method of a steroidal compound, in particular to a preparation method of hydrocortisone. The preparation method includes: sequentially subjecting chloride serving as the initiator to 9, 11-bromine hydroxyl preparation, 9, 11-reduction, 21-site esterification and 21-site hydrolysis to obtain the hydrocortisone. The preparation method has the advantages that the new preparation method has an industrialization value and can effectively control side reaction and increase reaction yield and quality; the design of the preparation does not involve with high-riskreaction, and industrialization can be achieved easily; the preparation method does not have high-pollution reaction, and environmental protection treatment pressure is relieved.
Facile synthesis of corticosteroids prodrugs from isolated hydrocortisone acetate and their quantum chemical calculations
Sethi, Arun,Singh, Ranvijay Pratap,Prakash, Rohit,Amandeep
, p. 860 - 866 (2016/12/18)
In the present research paper corticosteroids prodrugs of hydrocortisone acetate (1) have been synthesized, which was isolated from the flowers of Allamanda Violacea. The hydrocortisone acetate (1) was hydrolyzed to hydrocortisone (2) which was subsequently converted to prednisolone (3). Both the hydrocortisone (1) and prednisolone (2) underwent Steglich esterification with naproxen and Ibuprofen yielding compounds 11, 17 dihydroxy-21-(2-(6-methoxynaphthalene-2yl) propionoxy)-pregn-4-ene-3, 20-dione (4), 11, 17-dihydroxy-21-(2-(4-isobutylphenyl) propionoxy)-pregn-4-ene-3, 20-dione (5), 21-(2-(6-methoxynaphthalene-2-yl) propionoxy) 11,17-di-hydroxy-3,20-diketo-pregn-1,4-diene (6) and 11,17-di-hydroxy-3,20-diketo-pregn-1,4-diene-21-yl-2-(4-isobutylphenyl) propanoate (7). The synthesized compounds have been characterized with the help of spectroscopic techniques like 1H, 13C NMR, FT-IR spectroscopy and mass spectrometry. Density functional theory (DFT) with B3LYP functional and 6-31G (d, p) basis set has been used for the Quantum chemical calculations. The electronic properties such as frontier orbitals and band gap energies were calculated by TD-DFT approach. Intramolecular interactions have been identified by AIM (Atoms in Molecule) approach and vibrational wavenumbers have been calculated using DFT method. The reactivity and reactive site within the synthesized prodrugs have been examined with the help of reactivity descriptors. Dipole moment, polarizability and first static hyperpolarizability have been calculated to get a better insight of the properties of synthesized prodrugs. The molecular electrostatic potential (MEP) surface analysis has also been carried out.
A from the butyric acid of hydrocortisone in the mother liquor recovery of hydrocortisone method
-
Paragraph 0027; 0028; 0029; 0030; 0031; 0032, (2017/08/25)
The invention discloses a method for recycling hydrocortisone in hydrocortisone butyrate mother liquor. The method comprises the steps of adding refined hydrocortisone butyrate mother liquor into methyl alcohol to obtain a mixture, concentrating the mixture until the mixture is sticky, adding a mixed solvent for stirring and dissolving, and performing cooling; under the protection of inert gas, dropping alkaline liquid, performing heat preservation reaction after the alkaline liquid is added; performing neutralization, concentration, freezing filtration and drying to obtain hydrocortisone. By a reaction mode combining inert gas protection and the mixed solvent, the phenomenon that materials cannot be recycled because of decomposition of compounds due to breakage of the D-ring structure of steroid nucleus is effectively avoided. The method disclosed by the invention is easy to operate, short in treatment time, low in production cost and high in production safety and material stability, and the environment cannot be polluted; the recycling rate is high, so that the purity of recycled hydrocortisone is high; after being dried, hydrocortisone can be directly used as a raw material for producing hydrocortisone butyrate.
