57-83-0 Usage
Description
Progesterone, also known as pregn-4-en-3,20-dione, is a C21-steroid hormone that plays a crucial role in the female reproductive system. It is synthesized from cholesterol and is a biosynthetic precursor of all other steroid hormones. Progesterone is involved in the menstrual cycle, pregnancy, and embryogenesis in humans and other species. It is a white powder with a melting point of 121°C, stable in air, and has low toxicity. There are two crystal forms of progesterone, type-α and type-β, both insoluble in water but soluble in ethanol, ethyl ether, chloroform, acetone, dioxane, and concentrated sulfuric acid.
Uses
Used in Pharmaceutical Industry:
Progesterone is used as a hormone drug for promoting and maintaining uterine changes in the early stage of pregnancy. It is used in the treatment of habitual abortion, irregular menstruation, threatened abortion, amenorrhea, and premenopausal syndrome. It also plays a role in the feedback regulation of the hypothalamus and anterior pituitary, balancing animal reproductive hormones.
Used in Contraceptive Applications:
Progesterone is used as a contraceptive drug, working alongside estrogen to promote female estrus and inhibit ovulation.
Used in Gynecological Treatments:
Progesterone is used to treat dysmenorrhea, amenorrhea, and other symptoms related to the female reproductive system. It is also used in combination with other hormones to promote the development of mammary glands.
Used in Research and Development:
Progesterone is used as a progesterone receptor agonist and a mouse and human metabolite in research and development for understanding its role in various physiological processes.
Progesterone is also implicated in the etiology of breast cancer and is considered a contaminant of emerging concern (CECs). It is available in various forms, including oral micronized progesterone (Prometrium), intramuscular injections, and vaginal gels containing 4% or 8% progesterone. It was originally obtained from animal ovaries but is now prepared synthetically from plant sterol precursors. The discovery of 19-nortestosterones with progesterone activity has led to the development of synthetically modified progestins with significant therapeutic importance. However, progesterone is light-sensitive and should be protected from light.
Preparation
Progesterone can be obtained by oxidation of the pregnenolone. Dry toluene was added to a oven dried reaction kettle, and then cyclohexanone and pregnenolone were added in order with vigorous stirring to dissolve. Side product H2O was removed by Soxhlet extraction with toluene steam, aluminium isopropoxidequickly was added flowingly, the oxidation reaction was hold on at 115 oC for 2h, cooling to 80 oC, add 5% dilute sulfuric acid under stirring then stand by until water and toluene separated, the toluene layer was extracted with water to neutrality and then distillation off toluene and cyclohexanone. Cooling, filtering, filter cake was beated with petroleum, filtering, washing with petroleum, dried as crude progesterone. The crude product was dissolved in ethanol, decolorized by activated carbon, recrystallized to get the final product, yield 80%.
Another way to produce progesterone is choosing the 16-Dehydropregnenolone acetate as start material, treated consecutively by catalytic hydrogenation, alkali hydrolysis, oxidation by aluminum isopropoxide, to get the progesterone as final product.
Biological Functions
Progesterone is a hormone, produced primarily by the corpus luteum of the ovary but also by the placenta, that prepares the inner lining of the uterus for implantation ofa fertilized egg cell. If implantation fails, the corpus luteum degenerates and progesterone production ceases accordingly. If implantation occurs,the corpus luteum continues to secrete progesterone, under the influence of luteinizing hormone and prolactin, for several months of pregnancy,by which time the placenta has taken over this function. Duringpregnancy, progesterone maintains the constitution of the uterus and prevents further release of eggs from the ovary. Small amounts of progesterone are produced by the testes.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Progesterone is sensitive to light .
Hazard
A carcinogen (OSHA).
Health Hazard
ACUTE/CHRONIC HAZARDS: Progesterone may be absorbed through the skin.
Fire Hazard
Flash point data for Progesterone are not available; however, Progesterone is probably combustible.
Biological Activity
Endogenous progesterone receptor (PR) agonist (EC 50 = 0.5 nM).
Biochem/physiol Actions
Induces maturation and secretory activity of the uterine endothelium; suppresses ovulation. Progesterone is implicated in the etiology of breast cancer.
Pharmacology
During the second half of the menstrual cycle, progesterone promotes glandular growth in the endometrium, hyperemia of the uterus, thickening of the endometrium in preparation for implantation of a fertilized egg, and reduces the excitability of the uterus during pregnancy, inhibiting its activity and relaxing smooth muscles , allowing the embryo to grow safely. Under the joint action of estrogen, progesterone promotes the development of breast lobules and glands, so that the breasts can fully develop and prepare for lactation. Progesterone closes the cervix, reduces and thickens the mucus, and makes it difficult for sperm to penetrate; in large doses, it inhibits the secretion of pituitary gonadotropin through a negative feedback effect on the hypothalamus, resulting in the inhibition of ovulation. After ovulation, on the basis of the action of progesterone hormone, the endometrium continues to thicken and hyperemia, the glands proliferate and branch, from the proliferative phase to the secretory phase, which is conducive to the implantation and embryonic development of pregnant eggs. Progesterone inhibits uterine contractions and reduces the sensitivity of the uterus to oxytocin, allowing the fetus to grow safely. Progesterone competes against aldosterone, thereby promoting Na and Cl excretion and diuresis. Progesterone can slightly increase body temperature in normal women, so the basal body temperature in the luteal phase of the menstrual cycle is higher than that in the follicular phase.
Safety Profile
NTP 10th Report
on Carcinogens. IARC Cancer Review:
Animal Lirmted Evidence IMEMDT 21,491,79; Animal Sufficient Evidence
IMEMDT 6,135,74. EPA Genetic
Toxicology Program. Reported in EPA
TSCA Inventory.
SAFETY PROFILE: Confirmed carcinogen
with experimental carcinogenic,
neoplastigenic, tumorigenic, and teratogenic
data. Poison by intravenous and
intraperitoneal routes. Human teratogenic
effects by ingestion and parenteral routes:
developmental abnormalities of the
urogenital system. Human male
reproductive effects by intramuscular route:
changes in spermatogenesis, the prostate,
seminal vesicle, Cowper's gland and
accessory glands, impotence, and breast
development. Human female reproductive
effects by ingestion, parenteral, and
intravaginal routes: ferthty changes;
menstrual cycle changes and disorders;
uterus, cervix, and vagina changes.
Experimental reproductive effects. Human
mutation data reported. When heated to
decomposition it emits acrid smoke and
irritating fumes.
Synthesis
Progesterone, pregn-4-en-3,20-dione (28.3.1), is made by oxidizing pregnenolon
with aluminum isopropylate in the presence of cyclohexanone as a proton acceptor
(Oppenauer oxidation). Pregnenolon itself is made by subsequent oxidation
and further cleavage of the side chain of stigmasterin, a sterin of plant origin that is isolated
from soybeans.
Carcinogenicity
Progesterone is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Purification Methods
The form crystallises from EtOH with m 127-131o. The -form crystallises from pet ether or aqueous pet ether/aqueous Et2O with m 119-120o or 121o. It also crystallises from Et2O, Me2CO/EtOAc, MeOH, aqueous Et2O, aqueous MeOH, wet pet ether, Et2O/pet ether, pet ether/*C6H6, Et2O/pentane and isopropyl ether. The is at 240nm with log 4.25 (EtOH). [Wintersteiner & Allen J Biol Chem 107 max 321 1934, Beilstein 7 III 3648, 7 IV 2395.]
Check Digit Verification of cas no
The CAS Registry Mumber 57-83-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 7 respectively; the second part has 2 digits, 8 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 57-83:
(4*5)+(3*7)+(2*8)+(1*3)=60
60 % 10 = 0
So 57-83-0 is a valid CAS Registry Number.
InChI:InChI=1/C24H34O4/c1-14-12-18-19(22(4)9-6-17(27)13-21(14)22)7-10-23(5)20(18)8-11-24(23,15(2)25)28-16(3)26/h13-14,18-20H,6-12H2,1-5H3/t14-,18+,19-,20-,22+,23-,24-/m0/s1
57-83-0Relevant articles and documents
Regulation of steroidogenesis in the ovine corpus luteum
Silavin,Moss,Niswender
, p. 229 - 241 (1980)
To examine the factor affecting LH-induced progesterone production in vitro in ovine luteal slices, an experimental procedure was employed wherein each slice served as its own control. The role of microfilaments in steroidogenesis was studied in luteal slices treated with cytochalasin B (an inhibitor of microfilament function). Cytochalasin B treatment resulted in significant reduction of progesterone production by luteal slices in response to LH and the addition of serum to the medium did not alter this effect. The ability of luteal slices to respond to LH with increased progesterone secretion was restored when cytochalasin B was removed from the medium. Further studies indicated that inhibition of LH-induced progesterone production by treatment with cytochalasin B was not a result of a change in: 1) cyclic adenosine 3'-5'-monophosphate production in response to LH; 2) mitochondrial membrane permeability to cholesterol; or 3) activity of 3β-hydroxysteroid dehydrogenase, Δ5, Δ4-isomerase enzyme complex. The possibility existed that microfilaments were necessary for cholesterol transport to mitochondria in response to LH stimulation. However, mitochondrial cholesterol content was unchanged in response to LH in the presence or absence of aminoglutethimide (an inhibitor of cholesterol side-chain cleavage enzyme activity) as determined by uptake of 3H-cholesterol or total content determined by gas-liquid chormatography. Further, treatment with cytochalasin B had no effect on mitochondrial cholesterol content. These results suggest a role for microfilaments in LH-induced progesterone production at a point prior to the conversion of cholesterol to pregnenolone.
Fujimoto,Prager
, p. 3259 (1953)
Soft drugs: Thiazolidine-type derivatives of progesterone and testosterone
Bodor,Sloan
, p. 514 - 520 (1982)
Progesterone and testosterone are natural soft drugs, but to be used as drugs, their fast and facile metabolism must be prevented and their delivery controlled. A prodrug-soft drug combination can serve this purpose. Thiazolidines of testosterone, testosterone 17-proprionate and progesterone were synthesized from the reaction of cysteine alkyl esters, N-methylaminoethanethiol, and mercaptamine and their hydrochlorides with the appropriate steroids. The thiazolidines function as bioreversible derivatives of the parent steroids.
The catalytic mechanism of the 3-ketosteroid isomerase of Digitalis lanata involves an intramolecular proton transfer and the activity is not associated with the 3β-hydroxysteroid dehydrogenase activity
Meitinger, Nadine,Munkert, Jennifer,Maia de Pádua, Rodrigo,de Souza Filho, José Dias,Maid, Harald,Bauer, Walter,Braga, Fern?o Castro,Kreis, Wolfgang
, p. 1567 - 1571 (2016)
The isomerization of the Δ5-3-ketosteroid isoprogesterone into the Δ4-3-ketosteroid progesterone has been examined with recombinant 3β-hydroxysteroid dehydrogenase from Digitalis lanata (rDl3βHSD), partially purified 3-ketosteroid isomerase from Digitalis lanata (Dl3KSI) and under non-enzymatic conditions in deuterium oxide (D2O). Studies indicate that the isomerization catalyzed by the Dl3KSI proceeds without significant isotope exchange between the medium and the steroid and thus involves an intramolecular proton transfer consistent with the mechanism of the bacterial 3-ketosteroid isomerase of Pseudomonas testosteroni. For the rDl3βHSD as well as under non-enzymatic conditions deuterium was incorporated from the incubation buffer during isomerization. Together with a comparison of the rate of isomerization under the different conditions, it was demonstrated that rDl3βHSD does not possess 3-ketosteroid isomerase activity.
One-Pot Deoxygenation and Substitution of Alcohols Mediated by Sulfuryl Fluoride
Epifanov, Maxim,Mo, Jia Yi,Dubois, Rudy,Yu, Hao,Sammis, Glenn M.
, p. 3768 - 3777 (2021/03/01)
Sulfuryl fluoride is a valuable reagent for the one-pot activation and derivatization of aliphatic alcohols, but the highly reactive alkyl fluorosulfate intermediates limit both the types of reactions that can be accessed as well as the scope. Herein, we report the SO2F2-mediated alcohol substitution and deoxygenation method that relies on the conversion of fluorosulfates to alkyl halide intermediates. This strategy allows the expansion of SO2F2-mediated one-pot processes to include radical reactions, where the alkyl halides can also be exploited in the one-pot deoxygenation of primary alcohols under mild conditions (52-95% yield). This strategy can also enhance the scope of substitutions to nucleophiles that are previously incompatible with one-pot SO2F2-mediated alcohol activation and enables substitution of primary and secondary alcohols in 54-95% yield. Chiral secondary alcohols undergo a highly stereospecific (90-98% ee) double nucleophilic displacement with an overall retention of configuration.
Zn-Mediated Hydrodeoxygenation of Tertiary Alkyl Oxalates
Ye, Yang,Ma, Guobin,Yao, Ken,Gong, Hegui
, p. 1625 - 1628 (2021/01/18)
Herein we describe a general, mild, and scalable method for hydrodeoxygenation of readily accessible tertiary alkyl oxalates by Zn/silane under Ni-catalyzed conditions. The reduction method is suitable for an array of structural motifs derived from tertiary alcohols that bear diverse functional groups, including the synthesis of a key intermediate en route to estrone.