2203-97-6

Basic information

• Product Name: Hydrocortisone 21-hemisuccinate
• Synonyms: cortisolsuccinate;hydrocortisone21-succinate;saxizon;hydrocortisone 21-(hydrogen succinate);hydrocortisone 21-hemisuccinate*free acid;11β,17α,21-trihydroxy-4-pregnene-3,20-dione 21-hemisuccinate;HYDROCORTISONEHEMISUCCINATE(ANHYDROUS);Cortisol, 21-(hydrogen succinate) (8CI)
• CAS NO: 2203-97-6
• Molecular Formula: C₂₅H₃₄O₈
• Molecular Weight: 462.53
• EINECS: 218-612-3
• Product Categories: Steroids;Steroid and Hormone
• Mol File: 2203-97-6.mol

Chemical Properties

• Melting Point: 170～172℃
• Boiling Point: 685.5 °C at 760 mmHg
• Flash Point: 231.1 °C
• Appearance: /
• Density: 1.33 g/cm³
• Refractive Index: 1.587
• Storage Temp.: −20°C
• Solubility: Practically insoluble in water, freely soluble in acetone and in anhydrous ethanol. It dissolves in dilute solutions of alkali carbonates and alkali hydroxides.
• PKA: pKa 5.10/5.64(20% aq EtOH/50% aq EtOH) (Uncertain)
• CAS DataBase Reference: Hydrocortisone 21-hemisuccinate(CAS DataBase Reference)
• NIST Chemistry Reference: Hydrocortisone 21-hemisuccinate(2203-97-6)
• EPA Substance Registry System: Hydrocortisone 21-hemisuccinate(2203-97-6)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• RTECS: TU5010147
• Hazardous Substances Data: 2203-97-6(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Hydrocortisone 21-hemisuccinate is used as a glucocorticoid for its anti-inflammatory and immunosuppressive properties. It is particularly useful in treating various conditions such as rheumatoid arthritis, lupus, and other autoimmune disorders, as well as in managing severe allergies and asthma.
Used in Analytical Chemistry:
Hydrocortisone 21-hemisuccinate is used as an analytical and chromatography reagent due to its specific chemical properties, which make it suitable for various laboratory applications and techniques in the field of analytical chemistry.

InChI:InChI=1/C25H34O8/c1-23-9-7-15(26)11-14(23)3-4-16-17-8-10-25(32,24(17,2)12-18(27)22(16)23)19(28)13-33-21(31)6-5-20(29)30/h11,16-18,22,27,32H,3-10,12-13H2,1-2H3,(H,29,30)/t16-,17-,18-,22?,23-,24-,25-/m0/s1

Synthetic route

succinic acid anhydride (108-30-5) + HYDROCORTISONE (50-23-7) → hydrocortisone hemisuccinate (2203-97-6)

Conditions	Yield
With pyridine at 20℃; for 24h;	98%
With pyridine for 5h; Heating;	94%
Stage #1: succinic acid anhydride; HYDROCORTISONE With dmap In tetrahydrofuran; N,N-dimethyl-formamide at 45℃; for 4h; Stage #2: In tetrahydrofuran; N,N-dimethyl-formamide; acetone at 0 - 10℃; for 2h;	89%

succinic acid anhydride (108-30-5) + HYDROCORTISONE (50-23-7) → hydrocortisone hemisuccinate (2203-97-6)

Conditions	Yield
With pyridine at 20℃; for 24h;	98%
With pyridine for 5h; Heating;	94%
Stage #1: succinic acid anhydride; HYDROCORTISONE With dmap In tetrahydrofuran; N,N-dimethyl-formamide at 45℃; for 4h; Stage #2: In tetrahydrofuran; N,N-dimethyl-formamide; acetone at 0 - 10℃; for 2h;	89%

4-nitro-phenol (100-02-7) + hydrocortisone hemisuccinate (2203-97-6) → hydrocortisone-21-O-β-carbonylpropionic acid p-nitrophenolic ester (147930-86-7)

Conditions	Yield
With dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 24h;	95%
With dicyclohexyl-carbodiimide In tetrahydrofuran at 0 - 20℃; for 26h;	95%

hydrocortisone hemisuccinate (2203-97-6) + prednisolone-21-O-β-carbonylpropionyl-His-Gly-Lys-OH (757954-25-9) → Nα-(prednisolone-21-O-β-carbonylpropionyl)-His-Gly-Nε-(hydrocortisone-21-O-β-carbonyl-propionyl)-Lys-OH

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 40h;	74%

hydrocortisone hemisuccinate (2203-97-6) + 6--amino-2,3-dihydrophthalazine-1,4-dione (78544-61-3) → cortisol-aminopentyl ethyl isoluminol conjugate (76773-85-8)

Conditions	Yield
With 1-hydroxy-pyrrolidine-2,5-dione; carbodiimide 1.) DMF, r.t., 2.) DMF, 4 h, r.t.; Multistep reaction;

hydrocortisone hemisuccinate (2203-97-6) → HYDROCORTISONE (50-23-7)

Conditions	Yield
With tetramethyl ammoniumhydroxide; tetrazolium blue In ethanol Rate constant; Ambient temperature; reaction of corticosteroids and their hemisuccinate esters with blue tetrazolium under USP assay conditions, hydrolysis of esters, effect of water content, kinetic study by HPLC;

monophenylsulfonylfuroxan + hydrocortisone hemisuccinate (2203-97-6) → 4-(4-benzenesulfonyl-5-oxy-furazan-3-yl)-4-oxo-butyric acid 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

4-(2-hydroxyethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-N-oxide + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 2-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-ethyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

1-methyl-3-[2-oxido-3-(phenylsulfonyl)-1,2,5-oxadiazol-4-yloxy]propan-1-ol + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 3-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-1-methyl-propyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

4-(4-hydroxybutoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 4-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-butyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

4-(2-(2-hydroxyethoxy)ethoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 2-[2-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-ethoxy]-ethyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

4-(4-(hydroxymethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 4-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-benzyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

4-(4-(2-hydroxyethyl)phenoxy)-3-(phenylsulfonyl)-1,2,5-oxadiazole 2-oxide + hydrocortisone hemisuccinate (2203-97-6) → succinic acid 2-[4-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-phenyl]-ethyl ester 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

hydrocortisone hemisuccinate (2203-97-6) + 4-(2-aminoethoxy)-3-(benzenesulfonyl)-1,2,5-oxadiazole-2-oxide (186408-95-7) → N-[2-(4-benzenesulfonyl-5-oxy-furazan-3-yloxy)-ethyl]-succinamic acid 2-(11,17-dihydroxy-10,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl)-2-oxo-ethyl ester

Conditions	Yield
With dmap; dicyclohexyl-carbodiimide

hydrocortisone hemisuccinate (2203-97-6) → hydrocortisone-21-O-β-carbonylpropionyl-Glu-Asp-Gly-OH

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / DCC / tetrahydrofuran / 26 h / 0 - 20 °C 2: 79 percent / N-hydroxysuccinimide; DCC / tetrahydrofuran / 40 h / 20 °C View Scheme

hydrocortisone hemisuccinate (2203-97-6) → hydrocortisone-21-O-β-carbonylpropionyl-His-Gly-Glu-OH

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / DCC / tetrahydrofuran / 26 h / 0 - 20 °C 2: 80 percent / N-hydroxysuccinimide; DCC / tetrahydrofuran / 40 h / 20 °C View Scheme

hydrocortisone hemisuccinate (2203-97-6) → hydrocortison-21-O-succinyl-tyrosyl-arginine

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / DCC / tetrahydrofuran / 24 h / 20 °C 2: 51 percent / HOBt; N-methyl morpholine / dimethylformamide / 48 h / 20 °C / pH 9 View Scheme

Upstream product

• 108-30-5 succinic acid anhydride 
• 50-23-7 HYDROCORTISONE 

Downstream Products

• 147930-86-7 hydrocortisone-21-O-β-carbonylpropionic acid p-nitrophenolic ester 
• 50-23-7 HYDROCORTISONE 
• 76773-85-8 cortisol-aminopentyl ethyl isoluminol conjugate 

Relevant articles and documents

Preparation method of hydrocortisone sodium succinate

The invention discloses a preparation method of hydrocortisone sodium succinate. The method comprises the steps of preparing hydrocortisone succinic acid monoester by using succinic anhydride and hydrocortisone as raw materials; and performing a reaction by using the hydrocortisone succinic acid monoester as a raw material at a low temperature, and after the reaction is completed, performing treatment on the reaction liquid by adopting acetone with a temperature of about -20 DEG C to obtain the hydrocortisone sodium succinate. The process conditions adopted in the method provided by the invention are as follows: the sodium salt is generated at the low temperature, then the reaction liquid is added into a large amount of acetone, filtering is performed, the filter cake is washed by using the acetone and water, and finally vacuum drying is performed to remove the acetone; the process of high-temperature steaming is avoided, so that the product is stable, and has a high yield and a good state; the purity can reach 97% or more during reaction, and after purification, the product is in full compliance with the Chinese Pharmacopoeia standard; and the acetone can be recycled, so that theproduction costs are saved; therefore, the solution is suitable for industrial production, and the product quality is good.

Production process of hydrocortisone hemisuccinate

The invention discloses a production process of hydrocortisone hemisuccinate. The production process comprises a step of enabling hydrocortisone to react with succinic anhydride in an acetone solventby using triethylamine as a catalyst, wherein a mass ratio of the hydrocortisone and the succinic anhydride is 1 to (0.7 to 1.1), a mass ratio of the hydrocortisone and the acetone is 1 to (3 to 5), and a mass ratio of the hydrocortisone and the triethylamine is 1 to (0.2 to 0.5). According to the production process of the hydrocortisone hemisuccinate disclosed by the invention, the effects that the yield is greatly increased and the environment is friendly are also achieved while the hydrocortisone hemisuccinate uses pyridine or dimethyl sulfoxide as the solvent at the same time.

Magnetic particle-based hydrocortisone chemiluminescence immune assay method and kit

The invention discloses a fully-automatic magnetic particle-based hydrocortisone chemiluminescence immune assay method and application thereof. Immunomagnetic beads are coated by goat anti rabbit, antigen is detected by a chemiluminescent marker, a specific antibody of hydrocortisone is applied, a competitive response mode is established, a fully-automatic chemiluminescence immune assay serves asa detection tool, and the hydrocortisone is quantitatively detected according to the measured luminous value. According to the established method, the maximal detection range of the hydrocortisone reaches to 0.42 to 72.27 ng/mL, the detection limit is 0.12 ng/mL, the sensitivity can reach to 5.57 ng/mL and the recovery rate is 84.3 to 102.3 percent. According to the method, the detection process can realize full automation, the influence by professional testing personnel is not considered, the whole detection process is rapid and can be completed only by about 40 minutes, the detection limit is low, the sensitivity is high, the linear range is wide, the market requirement is met and good market application prospect is achieved.

Design and synthesis of furoxan-based nitric oxide-releasing glucocorticoid derivatives with potent anti-inflammatory activity and improved safety

A series of furoxan-based nitric oxide-releasing glucocorticoid derivatives was synthesized. The pharmacological assays indicated that three compounds, including I4, I5, and I6, had anti-inflammatory activity. Furthermore compared with the leading compound hydrocortisone the safety of I6 was greatly improved. Due to releasing NO in vivo the side effects of glucocorticoids, including hypertension and osteoporosis, were effectively avoided.

The synthesis and immunosuppressive activities of steroid-urotoxin linkers

The urotoxins (Glu-Asp-Gly-OH, His-Gly-Glu-OH, His-Gly-Lys-OH, and His-Gly-Lys-NHNH2) were introduced into the convenient sites of hydrocortisone and prednisolone via the amidation or condensation reactions to form the corresponding linkers 7a-d, 8a-d, 9a,b, and 10a,b in acceptable yields. The bioassays such as prolongation of heterotopic transplanted cardiac tissue survival in vivo, inhibitory effects on phagocytosis of mouse peritoneal macrophages and concanavalin (ConA) or lipopolysaccharide (LPS) induced proliferation of mouse spleen lymphocytes in vitro show that at the comparable concentrations the immunosuppressive activities of the steroid-urotoxin linkers 7a-d, 8a-d, 9a,b, and 10a,b were higher than that of hydrocortisone, prednisolone, and the urotoxins alone, as well as significantly higher than that of the mixture of hydrocortisone and urotoxins or prednisolone and urotoxins. The so-called 'permissive action' may be responsible for the enhancement of the mentioned bioactivities of the steroid-urotoxin linkers 7a-d, 8a-d, 9a,b, and 10a,b.

Preparation of europium-labeled derivatives of cortisol for time-resolved fluoroimmunoassays

Cortisol 3-(O-carboxymethyl)oxime, 6- and 21-hemisuccinoxycortisol, and Cortisol 7-carboxyethyl thioether were synthesized. These carboxyl derivatives were labeled using a described general labeling method with a europium chelate. The labeled steroids were tested in a competitive time-resolved fluoroimmunoassay using antibodies raised against cortisol. Only the site-homologous antigen-antibody pairs underwent immunoreaction and gave satisfactory calibration curves.