850-52-2

Basic information

• Product Name: Altrenogest
• Synonyms: 11-trien-3-one,17-alpha-allyl-17-hydroxy-estra-9;17-allyltrenbolone;17-alpha-allyl-estratriene-4,9,11,17-beta-ol-3-one;17-hydroxy-17-(2-propenyl)-(17-beta)-estra-11-trien-3-one;D02840;14-hydroxy-15-Methyl-14-(prop-2-en-1-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-1,6,16-trien-5-one;(17β)-17-Hydroxy-17-(2-propen-1-yl)estra-4,9,11-trien-3-one;(17β)-17-Hydroxy-17-(2-propenyl)estra-4,9,11-trien-3-one
• CAS NO: 850-52-2
• Molecular Formula: C₂₁H₂₆O₂
• Molecular Weight: 310.43
• EINECS: 212-703-1
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Steroid and Hormone;FLUDARA;Hormone
• Mol File: 850-52-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 120°
• Boiling Point: 390.58°C (rough estimate)
• Flash Point: 210.1 °C
• Appearance: Slightly yellow powder
• Density: 1.0865 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.4900 (estimate)
• Storage Temp.: 0-6°C
• PKA: 14.59±0.40(Predicted)
• Merck: 14,319
• CAS DataBase Reference: Altrenogest(CAS DataBase Reference)
• NIST Chemistry Reference: Altrenogest(850-52-2)
• EPA Substance Registry System: Altrenogest(850-52-2)

Safety Data

• WGK Germany: 3
• RTECS: KG7745000
• Hazardous Substances Data: 850-52-2(Hazardous Substances Data)

Usage

Description

Altrenogest is used to suppress estrus in mares in order to facilitate induction of normal estrous cycle activity. It is also used in mares to synchronize scheduled breeding activity. In the suppression of estrous behavior in mares, this is usually related to mares that are used as performance horses.

Application

Altrenogest is a progestin of the 19-nortestosterone group. As a veterinary medication, it is used extensively in the reproductive management of mares to control the reproductive cycle, help maintain pregnancy, and help with behavior modification. Altrenogest has been demonstrated to maintain pregnancy in oophorectomized mares and may be of benefit in mares that abort due to subtherapeutic progestin levels. Altrenogest is typically administered orally by applying directly on the base of the mare’s tongue or on the mare’s feed.

Uses

Different sources of media describe the Uses of 850-52-2 differently. You can refer to the following data:
1. Altrenogest is used for suppression of estrus. The mare will experience a predictable occurrence of estrus following drug withdrawal. This allows a regular cycle during the transition from winter anestrus to the physiological breeding season in mares with active ovaries. By managing the reproductive cycle, horse owners have more control over breeding procedures and the timing of the arrival of foals.
2. Altrenogest can be used as a synthetic progestational agent used in veterinary medicine for the control of estrus in mares and antineoplastic.

Biological Activity

Altrenogest suspension by NexGen is effective in normally cycling mares for minimizing the necessity for estrus detection, for the synchronization of estrus, and permitting scheduled breeding. Altrenogest is also effective in suppressing estrus expression in show mares or mares to be raced.

Interactions

Rifampin may increase the speed of metabolism of Regu-Mate.

in vitro

Altrenogest (Allyltrenbolone) is a progestogen structurally related to veterinary steroid trenbolone. Treatment of embryo-recipient mares with Altrenogest (Allyltrenbolone) appears to be beneficial in extending the degree of donor-recipient synchrony required for successful embryo transfer. The oil and gel Altrenogest (Allyltrenbolone) preparations are equally effective in modulating estrous behavior and time to estrus and ovulation. Altrenogest (Allyltrenbolone) treatment started late in diestrus appears to result in a high incidence of ovulation during treatment and when luteolysis and ovulation occur during treatment; the subsequent luteal phase is frequently prolonged due to failure of regression of the CL.

Chemical Properties

Pale Yellow Solid

Brand name

REGUMATE (Roussel-UCLAF, France).

Veterinary Drugs and Treatments

Altrenogest (Regu-Mate) is indicated (labeled) to suppress estrus in mares to allow a more predictable occurrence of estrus following withdrawal of the drug. It is used clinically to assist mares to establish normal cycles during the transitional period from anestrus to the normal breeding season often in conjunction with an artificial photoperiod. It is more effective in assisting in pregnancy attainment later in the transition period. Some authors (Squires et al. 1983) suggest selecting mares with considerable follicular activity (mares with one or more follicles 20 mm or greater in size) for treatment during the transitional phase. Mares that have been in estrus for 10 days or more and have active ovaries are also considered excellent candidates for progestin treatment.Altrenogest is effective in normally cycling mares for minimizing the necessity for estrus detection, for the synchronization of estrus, and permitting scheduled breeding. Estrus will ensue 2 – 5 days after treatment is completed and most mares ovulate between 8 – 15 days after withdrawal. Altrenogest is also effective in suppressing estrus expression in show mares or mares to be raced. Although the drug is labeled as contraindicated during pregnancy, it has been demonstrated to maintain pregnancy in oophorectomized mares and may be of benefit in mares that abort due to sub-therapeutic progestin levels.The product Matrix is labeled for synchronization of estrus in sexually mature gilts that have had at least one estrous cycle. Treatment with altrenogest results in estrus (standing heat) 4-9 days after completion of the 14-day treatment period.Altrenogest has been used in dogs for luteal insufficiency and as a treatment to prevent premature delivery.

InChI:InChI=1/C21H26O2/c1-3-10-21(23)12-9-19-18-6-4-14-13-15(22)5-7-16(14)17(18)8-11-20(19,21)2/h3,8,11,13,18-19,23H,1,4-7,9-10,12H2,2H3/t18-,19+,20+,21+/m1/s1

Synthetic route

C24H36O2Si → Altrenogest (850-52-2)

Conditions	Yield
With chloranil In dichloromethane at 20℃; for 1h; Time;	77.3%

17β-hydroxy-17α-propenylestrone-3-one-5,10-diene (23760-34-1) → Altrenogest (850-52-2)

Conditions	Yield
With chloranil; 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 0℃; Reagent/catalyst; Temperature;	75.8%
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In dichloromethane at 0 - 5℃; for 0.5h;

Trendione (4642-95-9) + allylmagnesium bromide (1730-25-2) → Altrenogest (850-52-2)

Conditions	Yield
Stage #1: Trendione With hydrogenchloride In ethylene glycol at 10 - 60℃; for 10h; Autoclave; Stage #2: allylmagnesium bromide In tetrahydrofuran; diethyl ether at 0℃; for 6h; Temperature; Solvent; Autoclave;	65%

allylmagnesium bromide (2622-05-1) + Trendione (4642-95-9) → Altrenogest (850-52-2)

Conditions	Yield
Stage #1: Trendione With hydrogenchloride In ethylene glycol at 25 - 60℃; for 10h; Autoclave; Stage #2: allylmagnesium bromide In tetrahydrofuran; diethyl ether at 0℃; for 5h; Autoclave;	60%

ethylene deltenone (5571-36-8) → Altrenogest (850-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: 2-methyltetrahydrofuran / 0.5 h / -5 - 0 °C / Inert atmosphere; Large scale 2: dichloro-acetic acid / water / -13 - -7 °C 3: 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane / 0.5 h / 0 - 5 °C View Scheme

4,9-Androstadiene-3,17-dione (5173-46-6) → Altrenogest (850-52-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: hydrogenchloride / water / 1 h / Reflux; Green chemistry 2: tetrahydrofuran / 2 h / -5 - 20 °C / Green chemistry 3: oxalic acid / acetone; methanol / 1 h / 15 - 20 °C / Inert atmosphere; Green chemistry 4: 2,3-dicyano-5,6-dichloro-p-benzoquinone / chloroform / 2 h / 30 °C / Green chemistry View Scheme
Multi-step reaction with 3 steps 1: lithium diisopropyl amide / tetrahydrofuran / 0.67 h / -40 - 20 °C / Industrial scale 2: tetrahydrofuran / 1 h / -15 - 20 °C / Industrial scale 3: chloranil / dichloromethane / 1 h / 20 °C View Scheme

17α-allyl-17β-hydroxyestra-4,9-dien-3-one → Altrenogest (850-52-2)

Conditions	Yield
With 2,3-dicyano-5,6-dichloro-p-benzoquinone In chloroform at 30℃; for 2h; Green chemistry;	60 g

C20H28O3 → Altrenogest (850-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: tetrahydrofuran / 2 h / -5 - 20 °C / Green chemistry 2: oxalic acid / acetone; methanol / 1 h / 15 - 20 °C / Inert atmosphere; Green chemistry 3: 2,3-dicyano-5,6-dichloro-p-benzoquinone / chloroform / 2 h / 30 °C / Green chemistry View Scheme

C23H34O3 → Altrenogest (850-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalic acid / acetone; methanol / 1 h / 15 - 20 °C / Inert atmosphere; Green chemistry 2: 2,3-dicyano-5,6-dichloro-p-benzoquinone / chloroform / 2 h / 30 °C / Green chemistry View Scheme

3,3-dimethoxy-estra-5(10),9(11)-diene-17-one (10109-76-9) → Altrenogest (850-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: diethyl ether / 20 °C / Inert atmosphere 2: sulfuric acid / acetone; water / 15 °C 3: chloranil; 2,3-dicyano-5,6-dichloro-p-benzoquinone / dichloromethane / 0 °C View Scheme

Altrenogest (850-52-2) → altrenogest

Conditions	Yield
In [D3]acetonitrile Schlenk technique; Sealed tube; UV-irradiation;	96%

Altrenogest (850-52-2) → propyltrenbolone

Conditions	Yield
With hydrogen; platinum(IV) oxide In methanol for 0.916667h;	81%

Altrenogest (850-52-2) → C21H21(2)H5O2 (1062120-74-4)

Conditions	Yield
With C21H49IrNP2; benzene-d6 at 20℃; for 20h;

1,1,1,3,5,5,5-heptamethyltrisiloxan (1873-88-7) + Altrenogest (850-52-2) → C28H46O4Si3 (1454834-22-0) + C28H46O4Si3 (1454834-23-1)

Conditions	Yield
Stage #1: 1,1,1,3,5,5,5-heptamethyltrisiloxan With 3,4,7,8-Tetramethyl-o-phenanthrolin; [{Ir(coe)2OH}2] In tetrahydrofuran at 20℃; for 0.0833333h; Glovebox; Inert atmosphere; Stage #2: Altrenogest With norbornene In tetrahydrofuran at 20 - 50℃; Sealed tube; Overall yield = 61 %; Overall yield = 65 mg; diastereoselective reaction;	A n/a B n/a

Upstream product

• 5173-46-6 4,9-Androstadiene-3,17-dione 
• 10109-76-9 3,3-dimethoxy-estra-5⁽¹⁰⁾,9⁽¹¹⁾-diene-17-one 
• 2622-05-1 allylmagnesium bromide 
• 4642-95-9 Trendione 
• 1730-25-2 allylmagnesium bromide 
• 23760-34-1 17β-hydroxy-17α-propenylestrone-3-one-5,10-diene 
• 5571-36-8 ethylene deltenone 

Relevant articles and documents

Preparation method of altrenogest

The invention discloses a preparation method of altrenogest, and belongs to the technical field of preparation and processing of pharmaceutical compounds. The method comprises the following steps: firstly, dissolving 3-protected estrogen-delta, delta-diene-17-one (1) in an organic solvent, and carrying out Grignard reaction to obtain 3-protected 17beta-hydroxyl-17alpha-propenyl-estra-delta, delta-diene (2); then carrying out hydrolysis reaction to obtain a dichloromethane solution of 17 beta-hydroxyl-17 alpha-propenyl estra-3-one-delta, delta-diene (3), and finally carrying out dehydrogenation reaction to obtain altrenogest. The method has the advantages of complete reaction, clear reaction complete judgment standard and few byproducts; reaction products in each step are easy to purify, the total mass yield of a final product is higher than 75%, and the purity reaches 99% or above; the method has the advantages of cheap and accessible raw materials, low cost, high operability and extremely high commercial competitiveness, is suitable for industrial large-scale production, and has favorable economic benefits.

Synthetic method of altrenogest

The invention discloses a synthetic method of altrenogest. The synthetic method comprises following steps: in an alcoholic solvent, an acid A and a compound M are added at 0 to 25 DEG C, an obtained mixture is heated to 30 to 90 DEG C for 5 to 24h of reaction, is cooled to room temperature, and then is subjected to distillation so as to remove the solvent; tetrahydrofuran is added, an obtained product is added at -10 to 10 DEG C, CH2CHCH2MgX is added dropwise, an obtained mixed product is heated to 25 to 60 DEG C for 2 to 5h of reaction, and then is cooled until the temperature is lower than 0 DEG C, an acid B is added dropwise so as to adjust pH value to 1 to 3, and then an obtained mixed material is heated to 60 DEG C for 5h of reaction; stirring is carried out for layering, an obtained upper layer product is subjected to drying and concentration with anhydrous sodium sulfate, and is refrigerated at a temperature of 5 DEG C or lower; recrystallization is carried out so as to obtain altrenogest. According to the synthetic method, altrenogest is prepared via one-pot method, the raw materials are easily available, the synthetic method is simple, and is friendly to the environment, cost is low, yield is high, and the synthetic method is especially suitable for industrialized production.

Synthesis method of altrenogest

The invention relates to a synthesis method of altrenogest. The synthesis method comprises the following steps: using Estra-4,9-diene-3,17-dione as a raw material, protecting 3-carbonyl in the form of ketal, then reacting 17-carbonyl with allylmagnesium bromide, deprotecting, and oxidizing to construct a 11,12-carbon-carbon double-bond reaction, thus synthesizing the altrenogest. The synthesis method provided by the invention has the advantages of accessible raw materials, simple process, environment friendliness, low cost and high yield.