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.
Development of a quantitative assay method for 3 beta-hydroxy-delta 5-steroid dehydrogenase in the rat testis.
Qujeq, Durdi
, p. 1071 - 1077 (2002)
We investigated the first step of the sex steroid hormone biosynthesis pathway by assaying the activities of 3 beta-hydroxy-delta 5-steroid dehydrogenase, the rate-limiting enzyme in this pathway. We have developed a simple and rapid colorimetric assay for 3 beta-hydroxy-delta 5-steroid dehydrogenase in rat testis. The supernatant from rat testis tissue homogenates were used for the enzyme assay. The enzyme activity was determined by measuring the absorbance at 570nm which indicates the rate of conversion of pregnenolone into progesterone in the presence of NAD, using phenazine methosulfate and nitro blue tetrazolium as the color reagent. The activity of this enzyme ranged from 4.57+/-1.34 to 10.56+/-2.13 nmol/mg protein/min with a mean activity of 8.96+/-1.27 nmol/mg protein/min. The K(m) of the enzyme at an optimum pH of 7.25 was about 4.7+/-0.12 nM.
IDENTIFICATION OF A UNIQUE SERTOLI CELL STEROID AS 3α-HYDROXY-4-PREGNEN-20-ONE (3α-DIHYDROPROGESTERONE: 3α-DHP)
Wiebe, J. P.
, p. 259 - 278 (1982)
An allylic steroid produced from progesterone by rat Sertoli cells and which does not appear to have been described previously as a product of gonadal or adrenal tissues has been isolated and identified as 3α-hydroxy-4-pregnen-20-one (3α-dihydroprogesterone; 3α-DHP). 3α-DHP appears to be a reactive molecule which is easily oxidized or dehydrated and its identification was possible by a combination of microchemical procedures, derivative formation, specific enzyme reaction, TLC, GC, HPLC, spectrophotometry and mass spectrometry.The biological functions of this Sertoli cell steroid are not known, but it is suggested that 3α-DHP is more than a metabolic waste product because (a) its production rate varies with age and is highest at the onset of meiosis, and (b) there appear to be specific receptors for it in the testis.
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.
3β-HYDROXYSTEROID DEHYDROGENASE/Δ5-4ISOMERASE ACTIVITY IN THE RHESUS MONKEY PLACENTA AND FETAL ADRENAL, TESTIS AND OVARY DURING LATE GESTATION
Sholl, Samuel A.
, p. 757 - 768 (1983)
3β-Hydroxysteroid dehydrogenase/Δ5-4isomerase (3β-HSDH) was measured in the rhesus monkey (Macaca mulatta) placenta, fetal adrenal (whole organ minus medulla), testis and ovary during late gestation (Days 145-162).Activities were evaluated from the conversion of -pregnenolone to progesterone.The maximum enzyme velocity (Vm) in adrenal microsomes (100,000 g pellet) was significantly higher (146 nmoles progesterone/h x mg-1 protein) than in microsomes from the other tissues.Testicular Vm was greater than either ovarian or placental Vm which were not different from one another (11.5 versus 1.9, 1.2 nmoles progesterone/h x mg-1 protein, respectively).Apparent Michaelis-Menten constants in the adrenal, placenta, testis and ovary averaged 1.8, 2.5, 0.27 and 0.16 μM, respectively.In some cases, substrate inhibition was noted.Estimated dissociation constants for pregnenolone were 2.3 μM (adrenal), 2.1 μM (placenta), 0.74 μM (testis) and 0.13 μM (ovary). 3β-HSDH was less active in a crude mitochondrial preparation from the fetal adrenal (10,000 g pellet) than in microsomes, whereas activity in the placenta and testis appeared to be equally distributed between mitochrondria and microsomes.Rate measurements were consistent with the apparent potentials of these organs to synthesize their characteristic hormones.Thus, 3β-HSDH activity may be an important rate determining step in hormone synthesis.The importance of substrate inhibition in progesterone formation remains to be assessed.
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.
Zn-Mediated Hydrodeoxygenation of Tertiary Alkyl Oxalates
Ye, Yang,Ma, Guobin,Yao, Ken,Gong, Hegui
supporting information, 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.
A Dual Role Reductase from Phytosterols Catabolism Enables the Efficient Production of Valuable Steroid Precursors
Peng, Haidong,Wang, Yaya,Jiang, Kai,Chen, Xinru,Zhang, Wenlu,Zhang, Yanan,Deng, Zixin,Qu, Xudong
supporting information, p. 5414 - 5420 (2021/02/05)
4-Androstenedione (4-AD) and progesterone (PG) are two of the most important precursors for synthesis of steroid drugs, however their current manufacturing processes suffer from low efficiency and severe environmental issues. In this study, we decipher a dual-role reductase (mnOpccR) in the phytosterols catabolism, which engages in two different metabolic branches to produce the key intermediate 20-hydroxymethyl pregn-4-ene-3-one (4-HBC) through a 4-e reduction of 3-oxo-4-pregnene-20-carboxyl-CoA (3-OPC-CoA) and 2-e reduction of 3-oxo-4-pregnene-20-carboxyl aldehyde (3-OPA), respectively. Inactivation or overexpression of mnOpccR in the Mycobacterium neoaurum can achieve exclusive production of either 4-AD or 4-HBC from phytosterols. By utilizing a two-step synthesis, 4-HBC can be efficiently converted into PG in a scalable manner (100 gram scale). This study deciphers a pivotal biosynthetic mechanism of phytosterol catabolism and provides very efficient production routes of 4-AD and PG.
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.
Preparation method of progesterone
-
Paragraph 0052-0081, (2021/04/26)
The invention discloses a preparation method of progesterone, which comprises the following steps of taking (20S)-20-hydroxymethyl pregna-4-ene-3-ketone as a raw material, and an acidic ionic liquid-based catalyst as a catalyst to react in a solvent, after the reaction is finished, separating the catalyst to obtain a reaction solution, sequentially concentrating the obtained reaction solution under normal pressure, adding water to separate out solid, filtering to obtain a progesterone crude product, and recrystallizing to obtain a progesterone fine product. The catalyst is prepared through catalysis of the acid controllable ionic liquid catalyst, the acid controllable ionic liquid catalyst has the characteristics of being high in designability, small in green pollution and the like, and when the acid controllable ionic liquid catalyst serves as the catalyst, the catalyst and a product are automatically layered after reaction; the catalyst can realize acidity controllability and regeneration through simple treatment after multiple cycles, so that the catalyst has a good application prospect.
