24 results about "Enediynone" patented technology

The present disclosure is drawn to compositions and methods for treating CNS disorders. In one embodiment, an oral pharmaceutical composition can comprise a therapeutically effective amount of pregn-4-ene-3,20-dione; and a pharmaceutically acceptable carrier that provides formation of either 3α-OH-5α-pregnan-20-one, or 3α-OH-5β-pregnan-20-one, or both in an amount sufficient to treat a CNS disorder when orally administered to a subject. In another embodiment, a method of treating a CNS disorder can comprise orally administering to a subject, a therapeutically effective amount of pregn-4-ene-3,20-dione that provides an amount of GABA receptor binding pregn-4-ene-3,20-dione metabolites that is sufficient to treat the CNS disorder. In another embodiment, a method of treating a CNS disorder can comprise orally administering to the subject, a therapeutically effective amount of pregn-4-ene-3,20-dione that provides an amount of 3α-OH-5α-pregnan-20-one, or 3α-OH-5β-pregnan-20-one, or both that is sufficient to treat the CNS disorder.

The invention relates to a rigid spiro compound and a preparation method and application thereof.The preparation method comprises the steps that 6-methylene-androstane-4-ene-3, 17-diketone (V) is dissolved in a mixed solution of dichloromethane and trifluoroacetic acid, reaction and reduced pressure distillation are conducted at the temperature of 20-25 DEG C, then extraction washing and distillation are conducted, a rigid spiro compound crude product can be obtained, and the rigid spiro compound is obtained. The crude product can be subjected to column chromatography separation and purification to obtain a refined rigid spiro compound (I). By adopting the preparation method, the friction and wear properties of the base oil are remarkably improved, and the base oil has lower friction coefficient and wear scar diameter, and has good application prospect as an antifriction and wear-resistant additive.

The invention relates to the technical field of pharmaceutical chemicals, in particular to a preparation method of 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone, and discloses a preparation method of 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone. The method comprises the following steps: S1, adding a 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone crude product into a mixed solution of a solvent A and a solvent B, heating to 25-35 DEG C, and stirring for dissolving until the solution is clear, so as to obtain a 11beta, 17alpha-dyhydroxyl-6 alpha-methylpregna-4-ene-3, 20-diketone crude product; s2, carrying out transposition elimination reaction; s3, carrying out acidification deprotection reaction; s4, adjusting the pH value; s5, standing and layering; s6, decoloring; s7, performing concentration; s8, cooling and crystallizing; s9, carrying out solid-liquid separation; and S10, carrying out vacuum drying, so as to obtain a finished product of the 11beta, 17alpha-dyhydroxyl-6 alpha-methyl pregna-4-ene-3, 20-diketone. The method has the characteristics of high yield and good product quality, is stable and is easy to realize industrial production.

The present application relates to a kind of from androsta 1, 4-diene-3, 17-dione starting synthesis of estren and the method of a kind of compound thereof.Especially, the present application provides a kind of preparation method of estren shown in formula I, comprising the following steps: in inert solvent, androsta-1, 4-diene-3, 17-dione (II) with reagent R4VX carries out demethylation aromatization reaction step directly to obtain estren (I);Wherein, the definition of reaction substrate, reagent and reaction condition is as claimed in claim or specification.The method is simple in operation, and good in selectivity, and product purity is high, suitable for industrial production.

The invention develops a cascade reaction strategy for realizing efficient synthesis of a caged ketal skeleton compound by taking Bronsted acid as a catalyst and taking a 3-hexene-2, 5-diketone derivative and a cinnamyl alcohol analogue as substrates, and synthesizes a natural product (+ / -)-catunaregin and a series of novel analogues of the natural product (+ / -)-catunaregin which are not reported in literatures. Important technical support and early-stage theoretical basis are provided for the creation of new drugs of the compounds. The cinnamyl alcohol analogue disclosed by the invention is simple and easy to prepare, wide in derivation range and low in price, and can better enrich the structural diversity of caged ketal skeleton compounds. The method disclosed by the invention can be prepared by a one-pot method, is efficient and rapid, simple to operate, short in reaction step, good in substrate tolerance, mild in reaction condition and wide in application range, and overcomes the defects of complex operation, harsh reaction conditions, substrate limitation, intolerant substrate functional groups, tedious steps and the like in the traditional reaction.

According to the present invention, the 21-hydroxy-17-(propionate) pregna-4-ene-3, 20-diketone is the effective androgen receptor inhibitor, and can be used as the androgen receptor inhibitor. The development of a high-purity synthesis process for preparing the compound has important significance. The preparation method comprises the following steps: by taking 21-hydroxy-17-(propionate) pregna-4-ene-3, 20-diketone containing isomer impurities as a raw material, selectively etherifying 21-hydroxyl silicon by using a silicon protecting group, so as to obtain an intermediate compound 3; the compound 3 is further converted to obtain a target compound 1, and a high-purity target product can be prepared by recrystallization. The synthesis process has the advantages of mild reaction conditions, high yield, simple post-treatment and the like.

The invention discloses a synthetic method of a high-grade intermediate of didrogesterone. The synthetic route of the invention is as shown in the specification, and more specifically, a compound 1 (9-hydroxyandrostenedione) is used as an initial raw material, a strategy of aromatization and dearomatization is adopted, and the synthetic route of bromination, A-ring aromatization, silicon-based protection of phenolic hydroxyl, carbonyl reduction, sulfonylation or halogenation of hydroxyl, deprotection of phenolic hydroxyl and dearomatization cyclization is adopted, so that the compound 1 (9-hydroxyandrostenedione) is obtained. According to the present invention, the non-natural steroid skeleton of the type of the didrogesterone can be obtained from the cheap 9-hydroxyandrostenedione, the high-grade intermediate (compound 8) of the didrogesterone can be efficiently and massively synthesized, and the sufficient raw material is provided for the further synthesis of the didrogesterone or the analogue thereof. # imgabs0 #

The invention provides a preparation method of 17 alpha-hydroxypregna-4-ene-3, 11, 20-triketone and an intermediate compound prepared by the preparation method, and relates to the technical field of medicine synthesis. The target product disclosed by the invention is prepared by taking 11 alpha-hydroxy-4-androstenedione as a starting material and carrying out six-step reaction, namely oxidation, ethynylation, ketalation, sulfonylation, etherification and hydrolysis. The starting material 11 alpha-hydroxy-4-androstenedione of the process is prepared from 4-androstenedione through enzyme transfer, and compared with 11 alpha, 17 alpha-dihydroxyprogesterone prepared from 17 alpha-hydroxyprogesterone through enzyme transfer, the enzyme transfer technology of the former is more mature, the conversion rate and the yield are higher, and the cost is lower. Meanwhile, the preparation method disclosed by the invention is easy to operate and implement in production and high in reaction conversion rate, avoids the use of a highly toxic reagent acetone cyanohydrin, and is more beneficial to large-scale industrial production.

The present invention relates to a method for preparing 21-(acetyloxy)-17-(1-oxopropoxy)-pregnane-4-ene-3,20-dione (VI) having the following formula: Compound (VI) can be used as a precursor for synthesizing the steroid compound clapriston for treating acne.

The invention provides a preparation method of 19-hydroxyestradione and an intermediate compound prepared by the preparation method. According to the method, 19-hydroxy-4-androstenedione is used as a raw material, and the 19-hydroxyestradione is prepared through four steps of reactions including sulfur condensation reaction, ketalation reaction, desulfurization and hydrolysis reaction. According to the preparation method disclosed by the invention, the synthesis of the 19-hydroxyestradienone is realized through a relatively simple and convenient route and shorter reaction steps, the use of a chromium oxidizing agent which is relatively serious in environmental pollution is avoided in the route, the safe industrial production is easy, and another feasible way is provided for commercial production of the 19-hydroxyestradienone.

The present disclosure is drawn to compositions and methods for treating CNS disorders. In one embodiment, an oral pharmaceutical composition can comprise a therapeutically effective amount of pregn-4-ene-3,20-dione; and a pharmaceutically acceptable carrier that provides formation of either 3α-OH-5α-pregnan-20-one, or 3α-OH-5β-pregnan-20-one, or both in an amount sufficient to treat a CNS disorder when orally administered to a subject. In another embodiment, a method of treating a CNS disorder can comprise orally administering to a subject, a therapeutically effective amount of pregn-4-ene-3,20-dione that provides an amount of GABA receptor binding pregn-4-ene-3,20-dione metabolites that is sufficient to treat the CNS disorder. In another embodiment, a method of treating a CNS disorder can comprise orally administering to the subject, a therapeutically effective amount of pregn-4-ene-3,20-dione that provides an amount of 3α-OH-5α-pregnan-20-one, or 3α-OH-5β-pregnan-20-one, or both that is sufficient to treat the CNS disorder.

To provide more effective therapeutic agents for skin diseases, and to provide a method for easily producing 9α-fluoro-11β-hydroxy-16β-methylandrosta-1,4-diene-3,17-dione.SOLUTION: Provided are a therapeutic agent for treating skin diseases, comprising one or more compounds (a) selected from the group consisting of compounds represented by formula (I) and compounds represented by formula (II). Provided is a method for producing 9α-fluoro-11β-hydroxy-16β-methylandrosta-1,4-diene-3,17-dione, comprising contacting one or more compounds (B) selected from the group consisting of betamethasone dipropionate, clobetasol propionate, betamethasone butyrate propionate, betamethasone valerate, clobetasone butyrate, and difluprednate with NaH.SELECTED DRAWING: None

The present invention relates to a process for the preparation of 21-(acetoxy)-17-(1-oxopropoxy)-pregn-4-ene-3, 20-dione (VI) having the following formula: the compound (VI) can be used as a precursor for the synthesis of a steroidal compound, i.e., Claristone, for the treatment of acne, and to a process for the preparation of 21-(acetoxy)-17-(1-oxopropoxy)-pregn-4-ene-3, 20-dione (VI).

The invention discloses a fluorohydrocortisone acetate impurity as well as a preparation method and application thereof, and belongs to the technical field of medicine synthesis. The invention provides a synthesis method of a fluorohydrocortisone acetate impurity, which comprises the following steps: oxidizing a key intermediate 9beta, 11beta-epoxy-17alpha-hydroxypregna-4-ene-3, 20-dione-21-acetate of fluorohydrocortisone acetate serving as a raw material to obtain an impurity II, carrying out ring-opening reaction on the impurity II and a fluorinating reagent to obtain an impurity III, and purifying the impurity III to obtain the fluorohydrocortisone acetate impurity. The purity of the prepared impurities II and III is up to 96.0% or above, and the impurity II and the impurity III of the fluorohydrocortisone acetate can be used as standard substances for monitoring the impurity content of the fluorohydrocortisone acetate and have high application value.

The application belongs to the field of organic chemical synthesis and medicinal chemistry, and particularly relates to the field of avarane type polycyclic heteroterpene compounds, and discloses that a 6 / 6 fused dienone tertiary alcohol is converted into a spiro[4.5]ene dienone skeleton through a rare stereospecific 1,2-alkyl migration reaction, de-OEt-1'-septosones B and C, 1'-septosones B and C and spiroetherones A and B are synthesized, and the structures of spiroetherones A and B are modified. Meanwhile, biological activity tests on the synthetic intermediates find that two new compounds exhibit significant anti-cancer activity on Hep G2, MV-4-11 and MOLT-4 cell lines, and IC epi values are as low as 2.1 μM. The application provides a new way and compound basis for the research and application of related heteroterpene compounds. epi values are as low as 2.1 μM. The application provides a new way and compound basis for the research and application of related heteroterpene compounds. 50 values are as low as 2.1 μM. The application provides a new way and compound basis for the research and application of related heteroterpene compounds.

The invention provides a method for synthesizing dehydroepiandrosterone through chemical-multienzyme coupling catalysis, and belongs to the technical field of pharmaceutical preparations with specific therapeutic activity. The method comprises the following steps: by taking 4-androstenedione as a substrate, carrying out esterification to synthesize 3-acetoxyandrostane-3, 5-diene-17-ketone; adding a lipolytic enzyme, and catalyzing the 3-acetoxyandrostane-3, 5-diene-17-ketone to synthesize the 5-androstenedione; ketoreductase and glucose dehydrogenase are added, and 5-androstenedione is catalyzed through double-enzyme coupling to synthesize DHEA. The method provided by the invention can realize efficient synthesis of DHEA.

The application discloses a preparation method of levonorgestrel, which comprises the following steps: iodine substitution is carried out on 18-hydroxy-4-estrene-3,17-dione to obtain a compound shown in formula 1; acetylene addition is carried out on the compound shown in formula 1 to obtain a compound shown in formula 2; ketal protection is carried out on the compound shown in formula 2 to obtain a compound shown in formula 3; methylation is carried out on the compound shown in formula 3 to obtain a compound shown in formula 4; and hydrolysis ketal reaction is carried out on the compound shown in formula 4 to obtain levonorgestrel. The preparation method is simple in operation, high in safety and friendly to environment, greatly reduces the safety, environmental protection and compliance costs in process production, is low in price of auxiliary materials, easy to purchase and convenient for industrial production and purchase, and is high in conversion rate.

The application discloses a detection method of coratrolon starting material related substances and application thereof, and belongs to the technical field of quality control of crude drugs. The method is detected by high performance liquid chromatography, and comprises the following steps: sample coratrolon starting material test solution into a high performance liquid chromatograph, record the chromatogram, calculate the corresponding content according to the peak area of each related substance, and the related substances include one or more of SM1-A, SM1-B, SM1-C, SM1-D, SM1-E and impurity B. The detection method has the advantages of good sensitivity and high accuracy, can be used for the detection of 17alpha, 21-dihydroxy progesterone-4-ene-3, 20-diketone-21-acetate related substances of coratrolon key starting material, and controls the quality of coratrolon from the source.

The invention discloses a preparation method of levonorgestrel, which comprises the following steps: carrying out iodine substitution on 18-hydroxy-4-estriene-3, 17-diketone to obtain a compound as shown in a formula 1; performing acetylene addition on the compound as shown in the formula 1 to obtain a compound as shown in a formula 2; performing ketal protection on the compound as shown in the formula 2 to obtain a compound as shown in a formula 3; methylating the compound as shown in the formula 3 to obtain a compound as shown in a formula 4; and carrying out hydrolysis ketal reaction on the compound as shown in the formula 4 to obtain levonorgestrel. The preparation method is easy and convenient to operate, high in safety and environmentally friendly, the safety, environmental protection and compliance cost in process production is greatly reduced, auxiliary materials are low in price and easy to obtain, industrial production and purchase are facilitated, and meanwhile the conversion rate is high.

The invention discloses a synthesis method of estradiol semihydrate. The synthesis method is particularly suitable for a process of synthesizing the estradiol semihydrate by taking ADD (1.4-androstenedione) as an initial raw material. The method comprises the following steps: firstly, carrying out ketal reaction on ADD and ethylene glycol to generate ketal, reacting the ketal with a lithiation reagent prepared from biphenyl, diphenylmethane, lithium and tetrahydrofuran to generate 17-ketal estrone, then hydrolyzing the 17-ketal estrone through inorganic acid to obtain estrone, reducing the estrone through a reducing agent to obtain an estradiol crude product, and purifying the estradiol crude product. And refining the estradiol crude product with an alcohol or ketone solvent and pure water, and drying to obtain the estradiol semihydrate. By using the method, impurities such as biphenyl, diphenylmethane and the like in lithiation reaction are removed in advance, the refining operation of the estrone is reduced (the refining of the estrone requires 30 times of volume of a solvent), the productivity is improved, the refining and drying processes of the estradiol semihydrate ensure that the content of crystal water is qualified, the single impurity of the synthesized product is less than 0.1%, and the yield is improved. The product meets the quality standards of the Chinese pharmacopoeia 2020 edition and the European pharmacopoeia 11 edition.

The present invention relates to a process for the preparation of 21-(acetyloxy)-17-(1-oxopropoxy)-pregn-4-ene-3,20-dione (VI) having the formula below:Compound (VI) can be used as a precursor for the synthesis of Clascoterone, a steroid used for the treatment of acne.

Provided herein is the first commensal microbial gene encoding an enzyme that catalyzes the conversion of androstenedione to epitestosterone in the gut bacterium Clostridium scindens (desF). Also provided is an important and unrecognized capability for epitestosterone in androgen receptor-dependent prostate cancer cell proliferation and the potential clinical relevance of this bacterial enzymatic pathway (desF) in prostate cancer. Additionally, it was discovered that bacterial isolates from urine or prostatectomy tissue are capable of androgen production and that urinary tract bacteria can exhibit 17β-hydroxysteroid dehydrogenase activity The gene in urinary isolates encoding 17β-hydroxysteroid dehydrogenase that catalyzes the conversion of androstenedione to testosterone was identified and named desG.

The invention discloses a preparation method of eplerenone and an intermediate of eplerenone, and belongs to the technical field of chemical synthesis of medicines, and the preparation method comprises the following steps: by taking 9 alpha-hydroxy-4-androstene-3, 17-diketone which is low in price and easy to obtain as an initial raw material, firstly, constructing a delta9, 11-double bond with high selectivity through an acidic dehydration reaction; then, a gamma-lactone ring is efficiently constructed through 3-position carbonyl protection, 17-position propynylation and oxidative cyclization reaction, and an intermediate delta 9, 11-canrenone is obtained; further efficiently introducing carboxyl into the C7 site of the intermediate through a photocatalytic flow chemical technology, and finally preparing eplerenone through esterification and 9alpha, 11alpha-stereoselective epoxidation. The method is novel in route design, avoids the difficulty in selectivity and the use of toxic reagents in the traditional method, and is mild in condition in each step, high in yield, high in purity and suitable for industrial production.