- An improved alternative norgestrel preparation
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Ethynyl cerium chloride, prepared in situ from ethynyl magnesium bromide or lithium acetylide and anhydrous cerium chloride efficiently added to 13-ethyl-3-methoxy-gona-3,5-diene-17-one 2. Aqueous HCl hydrolysis of intermediate enol ether 3 gave high yields of norgestrel 4.
- Ferri?o, Sergio,López-Tapia, Francisco,Salgado-Zamora, Héctor
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Read Online
- Steroidal Molecular Rotors with 1,4-Diethynylphenylene Rotators: Experimental and Theoretical Investigations Toward Seeking Efficient Properties
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Properly designed molecular rotors with sizable stators and a fast-moving rotator could provide efficient building blocks for amphidynamic crystals. Herein, we report the synthesis of steroidal compounds 1, 2, and 3 and their deuterated analogues 1D, 2D, and 3D envisioned to work as molecular rotors. The obtained compounds were characterized by attenuated total reflection-infrared, Raman, and circular dichroism (CD) spectroscopy measurements. The interpretation of spectra was supported by theoretical calculations using density functional theory methods. The analysis of the most characteristic bands confirmed different molecular dynamics of the rotors investigated. Angle-dependent polarized Raman spectra showed the crystallinity of some samples. Electronic CD (ECD) spectra of compounds 1-3 and their relevant deuterated analogues 1D-3D are identical. The increase of the band intensity with lowering the temperature shows that the equilibrium is shifted to the thermodynamically most stable conformer. ECD spectra simulated at the TDFFT level of theory for compound 3 were compared with experimental results. It was proved that conformer 3a, with a torsion angle of +50°, exhibits the best agreement with the experimental results. Simulated vibrational CD and IR spectra for conformer 3a and its deuterated analogue 3Da also display good agreement with experimental results. In light of our comprehensive investigations, we evidenced that steroidal compounds 1, 2, and 3 can work as molecular rotors.
- ?apiński, Andrzej,Farfán, Norberto,Górecki, Marcin,Jastrzebska, Izabella,Olszewska, Karolina,Runka, Tomasz,Santillan, Rosa
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p. 9625 - 9635
(2020/11/18)
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- Synthesis method of levonorgestrel
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The invention discloses a synthesis method of levonorgestrel, and belongs to the technical field of preparation and processing of medicines. According to the method, DL-ethyl diketone is used as an initial raw material, and the levonorgestrel disclosed by the invention is prepared through three steps of protection, ethynylation and hydrolysis. According to the preparation method of the levonorgestrel, the defects of a traditional process are overcome, a lithium ammonia reagent with large potential safety hazards is prevented from being used, reaction conditions are mild, operation is safe, andthe method is high in overall conversion rate, easy and convenient to operate, suitable for industrial production and wide in market prospect.
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Paragraph 0024; 0027
(2020/09/12)
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- Preparation method of levonorgestrel
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The invention discloses a preparation method of levonorgestrel, and belongs to the technical field of medicine preparation and processing. According to the method, 18-methylestra-2,5(10)-diene-3-methoxy-17-ketone is used as an initial raw material, and the levonorgestrel disclosed by the invention is prepared by virtue of two steps of ethynylation and hydrolysis. According to the preparation method of the levonorgestrel, the defects of a traditional process are overcome and reaction conditions are mild; the method is high in overall conversion rate, easy and convenient to operate, suitable forindustrial production and wide in market prospect.
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Paragraph 0025; 0027-0028; 0030-0031; 0033
(2020/09/20)
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- PROCESS FOR PREPARATION OF LEVONORGESTREL
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The present invention provides an improved process for preparation of levonorgestrel (3) which comprises of hydrolysis of 13β-ethyl-3-methoxy-17α-ethynyl-gona-2,5(10)-dien-17β-ol (2) with an acid in aprotic solvent. The present invention also provides a novel process for purification of crude levonorgestrel (3) by recrystallization from N,N-dimethyl formamide-water; methanol-water mixture.
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Paragraph 0048
(2014/01/07)
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- AN IMPROVED PROCESS FOR PREPARATION OF LEVONORGESTREL
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The present invention provides an improved process for preparation of levonorgestrel (3) which comprises of hydrolysis of 13 β-ethyl-3-methoxy-17α-ethynyl-gona-2,5(10)-dien-17β- o1 (2) with an acid in aprotic solvent. The present invention also provides a novel process for purification of crude levonorgestrel (3) by recrystallization from N,N-dimethyl formamide- water; methanol-water mixture.
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Page/Page column 10
(2012/09/10)
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- Levonorgestrel Crystallization
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The present invention provides for a crystalline polymorph of levonorgestrel and processes for making the same.
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Page/Page column 1
(2009/04/24)
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- Pharmaceutical combined preparation, kit and method for hormonal contraception
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PCT No. PCT/DE96/01192 Sec. 371 Date Jun. 3, 1998 Sec. 102(e) Date Jun. 3, 1998 PCT Filed Jun. 27, 1996 PCT Pub. No. WO97/01342 PCT Pub. Date Jan. 16, 1997The present invention describes a two-stage pharmaceutical combined preparation for hormonal contraception containing at least 30 daily unit doses, which preparation, in its first stage, comprises as hormonal active ingredient a combination of an oestrogen preparation and, in a dose that is at least sufficient to inhibit ovulation, a gestagen preparation, in single stage form and, in the second stage comprises as hormonal active ingredient an oestrogen preparation only, wherein the first stage comprises a minimum of 25 and a maximum of 77 daily discrete or continuous unit doses and the second stage comprises 5, 6 or 7 daily discrete or continuous unit doses, and wherein the total number of daily units is equal to the total number of days of the desired cycle of a minimum of 30 and a maximum of 84 days. This combined preparation, in the form of a monthly pack, which is used for female fertility control, permits as low as possible an oestrogen content in each individual unit dose and also has a low total hormone content per cycle of administration, with high contraceptive reliability, low incidence of follicle development, and satisfactory cycle control with reliable avoidance of intermediate bleeding as well as undesired side effects.
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- Pharmaceutical combination preparation for hormonal contraception
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The invention provides a pharmaceutical combination preparation with two hormone components in a packaging unit and intended for time-sequential oral administration, comprising a number of daily dosage units physically separate and individually removable in the packaging unit, whereby as a hormonal active ingredient a first hormone component contains in combination an estrogen preparation and in at least a dosage that is sufficient to inhibit ovulation a gestagen preparation, and as a hormonal active ingredient the second hormone component contains only an estrogen preparation, whereby the first hormone component comprises 23 or 24 daily units and the second hormone component comprises 4, 3 or 2 daily units, and between these two hormone components, 2 or 1 active ingredient-free daily units are present or 2 or 1 blank pill days are indicated, and the total number of hormone daily units and the active ingredient-free daily units or the blank pill days is equal to the total number of days of the desired cycle, but at least 28 days in length. This combination preparation is useful for female birth control, and allows for an estrogen content that is as low as possible in each individual dosage unit and also has a low total hormone content per administration cycle, with high contraceptive reliability, low incidence of follicular development, and satisfactory cycle control, with reliable avoidance of intracyclic menstrual bleeding as well as of undesirable side-effects.
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- Pharmaceutical combination preparation for hormonal contraception
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A pharmaceutical combination preparation with two hormone components that are manufactured physically separately in a packaging unit and that are intended for time-sequential oral administration, which in each case consist of a number of daily dosage units that are placed physically separately and are individually removable in the packaging unit. As a hormonal active ingredient, a first hormone component contains in combination an estrogen preparation and, in at least a dosage that is sufficient to inhibit ovulation, a gestagen preparation, and as a hormonal active ingredient the second hormone component contains only an estrogen preparation. The first hormone component comprises 23 or 24 daily units and the second hormone component comprises 4 to 10 daily units. The total number of hormone daily units is equal to the total number of days of the desired cycle, but at least 28 days in length. This combination preparation is used for female birth control, and allows for an estrogen content that is as low as possible in each individual dosage unit and also has a low total hormone content per administration cycle, with high contraceptive reliability, low incidence of follicular development, and satisfactory cycle control, with reliable avoidance of intracyclic menstrual bleeding as well as of undesirable side-effects.
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- Total synthesis with a chirogenic opening move demonstrated on steroids with estrane or 18a-homoestrane skeleton
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A concept of first choice for the synthesis of the title compounds had been proposed by Dane in the late 1930s. It was soon turned down, because the opening move - a chirogenic Diels-Alder reaction - did not work. With Lewis acids as mediators, however, a successful start has been achieved now. With Ti complexes of chelating ligands (Seebach's TADDOLs (= α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanols)), enantioselective formation of the desired adducts does occur. Efficient total syntheses of 2 and 3a have been accomplished.
- Quinkert,Del Grosso,Doring,Doring,Schenkel,Bauch,Dambacher,Bats,Zimmermann,Durner
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p. 1345 - 1391
(2007/10/02)
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- L-α-amino acids as transdermal penetration enhancers
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The disclosed invention provides methods and compositions ulilizing L-α-amino acids for enhancing the rate of penetration through the skin of both topical medicaments and of drugs employed for systemic administration. Fifteen L-α-amino acids were tested and found to enhance the rate of penetration of levonorgestrel through hairless mouse skin. These were Tryptophan, Glutamic Acid, Glycine, Proline, Alanine, Serine, Arginine, Aspartic Acid, Leucine, Isoleucine, Cysteine, Valine, α-Aminobutyric Acid, Norvaline and Norleucine. The effect of pH on the rate of penetration of the various amino acids was also examined and found to be unpredictable overall.
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- Synthesis of gon-4-enes
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1. A therapeutic composition having progestational activity comprising as active ingredient a 17-aliphatic carboxylic acid ester of 17α-ethynyl-18-methyl-19-nortestosterone and a pharmaceutical carrier for said compound.
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- Synthesis of 13-alkyl-gon-4-ones
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The preparation of 13-methylgon-4-enes and novel 13-polycarbonalkylgon-4-enes by a new total synthesis is described. 13-Alkylgon-4-enes having progestational, anabolic and androgenic activities are prepared by forming a tetracylic gonane structure unsaturated in the 1,3,5(10),9(11) and 14-positions, selectively reducing in the B- and C-rings, and converting the aromatic A-ring compounds so-produced to gon-4-enes by Birch reduction and hydrolysis.
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- Tetrahydropyran-2-ols
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Stereo-specific total synthesis of steroidal materials. 7-Substituted 3-oxo-1-heptenes or variants thereof are reacted with 2-alkylcycloalkane-1,3-diones yielding 3-substituted 6a β-alkyl-cyclopenta [f] [1] benzopyrans or naphtho [2,1-b] pyrans. These are then subjected to a selective catalytic hydrogenation followed by an introduction of a hydroxy, alkoxy or acyloxy group at the 4a-position to produce a 3-substituted 6a β,4a-hydroxy, alkoxy or acyloxy perhydrocyclopenta [f] [1] benzopyran or perhydro-naphtho [2,1-b] pyran. These latter compounds are then converted into 4- or 5-(3-oxoalkyl)perhydroindene-5-ones or perhydronaphthalene-6-ones which in turn can be converted to known steroidal materials by known methods.
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