Hydrocortisone CAS 50-23-7
Introduction：Basic information about Hydrocortisone CAS 50-23-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Hydrocortisone Basic information
| Product Name: | Hydrocortisone |
| Synonyms: | Hydrocortisone - CAS 50-23-7 - Calbiochem;Hydrocortisone, Chromatographic Standard - CAS 50-23-7 - Calbiochem;Hydrocortisone Acetate Impurity?A;Prednisolone Impurity 1（Prednisolone EP Impurity A）;Prednisolone EP Impurity A;21-Trihydroxypregn-4-ene-3;compoundf(kendall);Cortanal |
| CAS: | 50-23-7 |
| MF: | C21H30O5 |
| MW: | 362.47 |
| EINECS: | 200-020-1 |
| Product Categories: | Pharmaceutical intermediates;Steroids;Veterinaries;Inhibitors;TPI;Intermediates & Fine Chemicals;Pharmaceuticals;Steroid and Hormone;Hormone Drugs;HYDROCORTONE;Isolabel;adrenocortical hormones ' drug;API;50-23-7;APIs |
| Mol File: | 50-23-7.mol |
Hydrocortisone Chemical Properties
| Melting point | 211-214 °C(lit.) |
| alpha | 166 º (c=1, C2H5OH 25 ºC) |
| Boiling point | 414.06°C (rough estimate) |
| density | 1.0812 (rough estimate) |
| refractive index | 1.6120 (estimate) |
| Fp | 220°C |
| storage temp. | -20°C |
| solubility | H2O: 100 mg/mL |
| form | powder |
| color | White |
| PH | 5.0- 7.0 |
| biological source | non-animal source |
| Water Solubility | 319.7mg/L(25 ºC) |
| Decomposition | 220 ºC |
| Merck | 14,4787 |
| BRN | 1354819 |
| Stability: | Stable, but may be light sensitive. Incompatible with strong oxidizing agents. |
| Major Application | clinical testing clinical testing |
| InChIKey | JYGXADMDTFJGBT-VWUMJDOOSA-N |
| SMILES | C[C@]12CCC(=O)C=C1CC[C@H]3[C@@H]4CC[C@](O)(C(=O)CO)[C@@]4(C)C[C@H](O)[C@H]23 |
| LogP | 1.610 |
| CAS DataBase Reference | 50-23-7(CAS DataBase Reference) |
| NIST Chemistry Reference | Hydrocortisone(50-23-7) |
| EPA Substance Registry System | Hydrocortisone (50-23-7) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 62-63 |
| Safety Statements | 36/37 |
| WGK Germany | 3 |
| RTECS | GM8925000 |
| TSCA | TSCA listed |
| HS Code | 29372100 |
| Storage Class | 3 - Flammable liquids |
| Hazard Classifications | Acute Tox. 3 Dermal Acute Tox. 3 Inhalation Acute Tox. 3 Oral Flam. Liq. 2 STOT SE 1 |
| Hazardous Substances Data | 50-23-7(Hazardous Substances Data) |
| Toxicity | LD50 subcutaneous in mouse: > 500mg/kg |
| Chemical Properties | crystalline white powder |
| Originator | Hydrocortone,MSD,US,1952 |
| Uses | Principle glucocorticoid hormone produced by adrenal cortex. An anti-inflammatory hormone. |
| Uses | glucocorticoid, antiinflammatory |
| Uses | 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, SarnolHC, Penecort, Texacort, and many other branded products) may be purchased as ageneric drug. |
| Manufacturing Process | The following example from US Patent 2,602,769 illustrates the preparation of17-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% sodiumchloride and 0.3% yeast extract in tap water. To 200 ml of this sterilizedmedium was added an inoculum of the vegetative mycella of Cunninghamella blakesleeana. The spores had first been transferred from a sport slant to abroth medium and the broth medium was aerobically incubated at 24°C for 24to 72 hours in a .reciprocating shaker until the development of vegetativegrowth. The inoculated medium containing added vegetative mycella ofCunninghamella blakesleeana was incubated for 48 hours at 24°C followingwhich was added 66 mg of compound S, 11-desoxy-17-hydroxycorticosteronein solution in a minimum of ethanol, and incubation was maintained for 7hours at 24°C. The beer containing steroid was diluted with 800 ml ofacetone, shaken 1 hour on a reciprocating shaker and filtered. The cake wassuspended in 500 ml of acetone, shaken another hour and again filtered. Thefiltrates were combined and the acetone was volatilized under reducedpressure at 50°C. Acetone was then added, if necessary, to bring theconcentration to 20% acetone and this resulting aqueous acetone solution wasextracted five times each with one-third volume of Skellysolve B petroleumether to remove fatty materials. These extracts were back washed two timeswith one-tenth volume of 20% aqueous acetone and the washings were addedto the main acetone extract. The combined acetone extracts were extracted six times with one-fourthvolume of ethylene dichloride and the ethylene dichloride extract wasevaporated under vacuum to leave the steroid residue. This steroid residuewas taken up in a minimum of methylene chloride and applied to the top of acolumn packed with 30 grams of silica which had been previously trituratedwith 21 ml of ethylene glycol. Then various developing mixtures, saturatedwith ethylene glycol, were passed over the column. Cuts were made as eachsteroid was eluted as determined by the lowering of the absorption of light at240 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 andrefrigerated until crystals separated. This cold acetone mixture wascentrifuged and the supernatant liquid removed by pipette. To the remainingcrystals, a few drops of ice-cold ether-acetone, three to one mixture, wereadded, shaken, recentrifuged and the supernatant wash liquid removed bypipette. The ether-acetone wash was repeated. The resulting crystals weredried under vacuum yielding 3.3 mg of pure compound F, 17-hydroxycorticosterone. |
| Brand name | Acticort (Baker Norton); Ala-Cort (DelRay); 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 (XGen); 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 Agroup. Marker of allergy is tixocortol pivalate. |
| Mechanism of action | Hydrocortisone exhibits anti-shock, anti-allergy, and anti-inflammatory action. It raisessugar content in the blood, increases potassium secretion, and lowers sodium excretionfrom the body. It exhibits anti-metabolic action and reduces histamine synthesis in thebody. |
| Clinical Use | Hydrocortisone is endogenous, and it has both glucocorticoid and mineralocorticoid activity. It isthe fundamental structure by which the glucocorticoid and mineralocorticoid activities of all othercorticosteroids are judged. Functional groups that are essential for both mineralocorticoid andglucocorticoid activity include the pregnane skeleton with an all-trans backbone, the ringA-en-one system (?4-3-one ring A) and the 17β-ketol side chain (C-20-keto-C-21-hydroxy). Theglucocorticoid activity is enhanced by the C-11 and C-17 hydroxyl groups. Hydrocortisone can beused to treat severe asthmatic attacks that do not respond to conventional treatment. It isavailable as various ester forms. |
| Safety Profile | Poison by |
| Synthesis | Hydrocortisone, 11|?,17|á,21-trihydroxypregn-4-en-3,20-dione(27.1.8), is synthesized in various ways and from various compounds containing asteroid skeleton. According to one of them, hydrocortisone is synthesized from dextropregnenolone.The double bond between C16 and C17 of dextropregnenolone is oxidizedusing hydrogen peroxide in a base, forming an epoxide 27.1.1. Interacting this withhydrobromic acid opens the epoxide ring, forming 16-bromo-17-hydroxydextropregnenolone(27.1.2). The resulting bromo derivative undergoes debromination by hydrogenusing a palladium on carbon catalyst, and then the secondary hydroxyl groupundergoes esterification using formic acid in the presence of p-toluenesulfonic acid, giving3-formyloxy-17-hydroxydextropregnenolone (27.1.3). The resulting 3-formyloxy-17-hydroxydextropregnenolone undergoes bromination by bromine, which results inbromination of the C4¨CC5 double bond and the methyl group of acetyl moiety, whichforms a tribromo derivative 27.1.4. Reacting the product with sodium iodide results indehalogenation of the resulting vicinal dibromide, during which the double bond issimultaneously shifted into the position between carbon atoms C5 and C6 that gives thebromoketone 27.1.5. This is reacted with potassium acetate and then with acetic anhydridein the presence of p-toluenesulfonic acid, forming a diacetate 27.1.6. Taking intoaccount that unlike acetates, formates are easily oxidized and give exactly the sameproducts as do the corresponding alcohols, the resulting diacetate is oxidized in anOppenauer oxidation reaction, using aluminum isopropoxide and cyclohexanone as ahydrogen acceptor. During this, isomerization of the double bond into the primary positionbetween C4 and C5 simultaneously takes place, forming a stable, conjugatedvinylketone, after which the acetyl protection of both hydroxyl groups is hydrolyzedusing potassium hydroxide, giving 17-hydroxy-11-deoxycorticosterone (27.1.7). Thisundergoes microbiological oxidation at position C1, forming the desired hydrocortisone(27.1.8). Side reactions of microbiological oxidation using the very same microorganismscan cause hydroxylation of steroids in different positions, using easily accessibleprogesterone 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 mostcommonly 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 treatinghypovolemic shock, but low dose glucocorticoids probably reducemortality associated with septic shock. Glucocorticoids have been used in an attempt to treat practicallyevery malady that afflicts man or animal, but there are three broaduses and dosage ranges for use of these agents. 1) Replacement ofglucocorticoid 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., systemiclupus), allergic states, respiratory diseases (e.g., asthma), dermatologicdiseases (e.g., pemphigus, allergic dermatoses), hematologicdisorders (e.g., thrombocytopenias, autoimmune hemolytic anemias),neoplasias, nervous system disorders (increased CSF pressure),GI diseases (e.g., ulcerative colitis exacerbations), and renaldiseases (e.g., nephrotic syndrome). Some glucocorticoids are usedtopically in the eye and skin for various conditions or are injectedintra-articularly or intra-lesionally. The above listing is certainlynot complete. |
| target | TNF-α | IL Receptor | AP-1 | MMP(e.g.TIMP) | NF-kB | IkB | IKK |
| storage | Store at RT |
| 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.] |
Hydrocortisone Preparation Products And Raw materials
| Raw materials | Potassium borohydride-->Isopropyl acetate-->Semicarbazide-->Cortisone acetate-->Saponin-->CORTEXOLONE |
| Preparation Products | Deprodone propionate-->6,9-Difluoro-11,16,17,21-tetrahydroxypregna-1,4-diene-3,20-dione 21-acetate-->6alpha,9-difluoro-11beta,21-dihydroxypregna-1,4,16-triene-3,20-dione 21-acetate-->Triamcinolone 21-acetate-->Prednisone-->9-fluoro-11beta,21-dihydroxypregna-1,4,16-triene-3,20-dione 21-acetate-->9-Fluoropregna-1,4-diene-11,17,21-triol-3,20-dione17,21-diacetate-->3,17,21-Trihydroxypregna-3,5,9(11)-trien-20-one 3,17,21-triacetate-->Prednisolone-->6alpha,9-difluoro-11beta,17,21-trihydroxypregna-1,4-diene-3,20-dione 17,21-di(acetate)-->Anecortave Acetate-->6,9-Difluoropregn-4-ene-11,17,21-triol-3,20-dione17,21-diacetate-->Hydrocortisone acetate-->9,11-Epoxypregn-4-ene-17,21-diol-3,20-dione 21-acetate-->Pregna-4,9(11)-diene-17,21-diol-3,20-dione17,21-diacetate-->9,11-Epoxy-6-fluoro-17,21-dihydroxypregn-4-ene-3,20-dione-17,21-diacetate-->17,21-Diacetyloxy-9,11-epoxypregn-4-ene-3,20-dione-->Hydrocortisone Butyrate Propionate-->9-Bromo-11,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate-->9-Bromo-11,17,21-trihydroxypregn-4-ene-3,20-dione17,21-diacetate-->6-Fluoro-17,21-dihydroxypregna-4,9(11)-diene-3,20-dione 17,21-diacetate-->11alpha,17,21-trihydroxypregn-4-ene-3,20-dione 21-acetate |
