382-67-2

Basic information

• Product Name: Desoximetasone
• Synonyms: 9-FLUORO-11BETA,21-DIHYDROXY-16ALPHA-METHYLPREGNA-1,4-DIENE-3,20-DIONE;9-fluoro-11b,21-dihydroxy-16a-methylpregna-1,4-diene-3,20-dione;21-desoxybetamethasone;1,4-PREGNADIEN-9-ALPHA-FLUORO-16-ALPHA-METHYL-11-BETA, 21-DIOL-3,20-DIONE;DESOXIMETASONE;DESOXYMETASONE;17-deoxymethansone;17-desoximethasone
• CAS NO: 382-67-2
• Molecular Formula: C₂₂H₂₉FO₄
• Molecular Weight: 376.46
• EINECS: 206-845-3
• Product Categories: Steroids;Intermediates & Fine Chemicals;Pharmaceuticals;Steroid and Hormone
• Mol File: 382-67-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 213-215°C
• Boiling Point: 532.3 °C at 760 mmHg
• Flash Point: 275.7 °C
• Appearance: /
• Density: 376.46
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.574
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• PKA: 12.98±0.10(Predicted)
• CAS DataBase Reference: Desoximetasone(CAS DataBase Reference)
• NIST Chemistry Reference: Desoximetasone(382-67-2)
• EPA Substance Registry System: Desoximetasone(382-67-2)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-36/37/38-40-43
• Safety Statements: 22-26-36
• WGK Germany: 3
• RTECS: TU3834000
• Hazardous Substances Data: 382-67-2(Hazardous Substances Data)

Usage

Chemical Properties

Off-White Solid

Originator

Topicorte,Roussel,France,1968

Uses

Glucocorticoid anti-inflammatory. It is also found as an impurity in Dexamethasone (D298800).

Definition

ChEBI: Dexamethasone in which the hydroxy group at the 17alpha position is substituted by hydrogen. A synthetic corticosteroid with glucocorticoid activity, it is used as an anti-inflammatory and anti-pruritic in the treatment of various skin dis rders, including skin allergies and psoriasis.

Manufacturing Process

(a) Production of 16α-Methyl-4-Pregnene-11β,21-diol-3,20-Dione (= 16αMethylcorticosterone): A fermenter of stainless steel having a 50 liter capacity is charged with 30 liters of a nutrient solution containing: sterilized for ? hour at 120°C and after cooling, inoculated with a spore suspension of Curvularia lunata which is obtained by rinsing a seven day corn culture (15 grams corn) with approximately 100 cc of physiological sodium chloride solution.After two days of culturing at 25°C under stirring (220 revolutions per minute) and ventilating (1.65 m3/hr), 18 liters of the obtained culture are removed under sterile conditions and introduced into a fermenter of the same size charged with 28.2 liters of a nutrient solution containing:After 24 hours cultivation under stirring and ventilation as described above, 7.5 grams of 16α-methyldesoxycorticosterone, obtained by saponification of the corresponding 21-acetate and melting at 102-104°C, in 200 cc of ethanol are added and fermented under the same conditions for 28 hours.The course of the fermentation is tested by removal of samples, which are extracted with methyl isobutyl ketone. The extract is analyzed by paper chromatography in a system of dioxane + toluene/propylene glycol.After the end of the fermentation (28 hours) the culture broth is filtered off by suction over a large suction filter. The mycel residue is washed with water several times. The filtrate is extracted three times, each time with 10 liters of methyl isobutyl ketone. The extract is concentrated under vacuum in a circulating evaporator and in a round flask carefully dried under vacuum. The residue is crystallized from acetone/isopropyl ether. The melting point is 157- 158°C (fermentation yield = 60%). The pure product yield obtained after a second crystallization and chromatography of the mother liquor on silica gel amounts to 53% of the theoretical.(b) 16α-Methyl-9α-Fluoro-?4-Pregnene-11β,21-Diol-3,20-Dione: 7.5 grams of 16α-methyl-9α-fluoro-?4-pregnene-21-ol-3,20-dione-21-acetate, obtained from Step (a) by acetylating with acetic anhydride in pyridine followed by reaction with HF in pyridine at 0°C, are fermented for 36 hours with Curvularia lunata (Mutant NRRL 2380), whereby the 21-acetate group is simultaneously saponified, and then further worked up. The residue is extracted with MIBK, subjected to chromatography on silica gel and there is obtained from chloroform/ethyl acetate (2:1) an eluate containing the 11βhydroxy compound, which is further dehydrogenated as the crude product. (c) 16α-Methyl-9α-Fluoro-?1,4-Pregnadiene-11β,21-Diol-3,20-Dione: 16αmethyl-9α-fluoro-β4-pregnene-11β,21-diol-3,20-dione obtained as the crude product under Step (b) above, is fermented with Bacillus lentus for 30 hours and further worked up. The residue is extracted with methyl isobutyl ketone and there is obtained as the crude product 16α-methyl-9α-fluoro-?1,4- pregnadiene-11β,21-diol-3,20-dione.

Brand name

Topicort (Taro) [Name previously used: Desoxymethasone.].

Therapeutic Function

Antiinflammatory

General Description

Desoximetasone, 9-fluoro-11β, 21-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione, like clocortolone pivalate, lacks a C17α OH group inits structure.

InChI:InChI=1/C22H29FO4/c1-12-8-16-15-5-4-13-9-14(25)6-7-21(13,3)22(15,23)18(27)10-20(16,2)19(12)17(26)11-24/h6-7,9,12,15-16,18-19,24,27H,4-5,8,10-11H2,1-3H3/t12-,15+,16+,18?,19-,20+,21+,22+/m1/s1

Upstream product

• 50-02-2 dexamethasone 

Downstream Products

• 75262-69-0 (8S,9R,10S,11S,13S,14S,16R,17S)-9-Fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid 
• 25122-52-5 21-chloro-9α-fluoro-11β-hydroxy-16α-methyl-17α-propanoyloxy-1,4-pregnadiene-3,20-dione 

Relevant articles and documents

PROCESS FOR THE PREPARATION OF 17-DESOXY-CORTICOSTEROIDS

The present invention provides an improved process for the preparation of 17-desoxy corticosteroid derivatives in a single chemical step by reacting the 17-hydroxy starting material with an excess of Trimethylsilyl Iodide. The present invention is specifically advantageous in preparing 17-desoxy corticosteroid derivatives having one or more halogen groups at positions 2, 6, 7 or 9 of the corticosteroid such as Clocortolone or Desoximetasone.

Cytotoxic nucleoside-corticosteroid phosphodiesters

Nucleotides of nucleosides or bases having known cytotoxic activity are reacted with steroids, preferably corticosteroids, to form corresponding cytotoxic nucleoside-corticosteroid phosphodiester analogues of the formula: STR1 wherein: steroid is the residue formed by removal of a hydroxyl hydrogen atom from a natural or synthetic adrenal corticosteroid containing the characteristic cyclopentanophenanthrene nucleus which is esterified to the phosphate moiety at the 21-position; sugar is a naturally occurring pentose or deoxypentose in the furanose form, preferably ribose, deoxyribose, lyxose, xylose or arabinose and especially ribose, deoxyribose or arabinose, which is esterified to the phosphate moiety at the 5'-position and covalently bonded to the heterocycle moiety at the 1'-position to form a nucleoside; and heterocycle is a purine, pyrimidine, hydrogenated pyrimidine, triazolopurine or similar nucleoside base. The conjugates exhibit an enhanced therapeutic index as compared to the parent nucleoside or base compounds, and are thus useful cytotoxic, antiviral and antineoplastic agents.

Synthesis of 9α fluoro 16α methyl 17 desoxy prednisolone

-