- One-Step Chemo-, Regio- and Stereoselective Reduction of Ketosteroids to Hydroxysteroids over Zr-Containing MOF-808 Metal-Organic Frameworks
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Zr-containing MOF-808 is a very promising heterogeneous catalyst for the selective reduction of ketosteroids to the corresponding hydroxysteroids through a Meerwein-Ponndorf-Verley (MPV) reaction. Interestingly, the process leads to the diastereoselective synthesis of elusive 17α-hydroxy derivatives in one step, whereas most chemical and biological transformations produce the 17β-OH compounds, or they require several additional steps to convert 17β-OH into 17α-OH by inverting the configuration of the 17 center. Moreover, MOF-808 is found to be stable and reusable; it is also chemoselective (only keto groups are reduced, even in the presence of other reducible groups such as C=C bonds) and regioselective (in 3,17-diketosteroids only the keto group in position 17 is reduced, while the 3-keto group remains almost intact). The kinetic rate constant and thermodynamic parameters of estrone reduction to estradiol have been obtained by a detailed temperature-dependent kinetic analysis. The results evidence a major contribution of the entropic term, thus suggesting that the diastereoselectivity of the process is controlled by the confinement of the reaction inside the MOF cavities, where the Zr4+ active sites are located.
- Llabrés i Xamena, F. X.,Mautschke, H.-H.
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p. 10766 - 10775
(2021/06/15)
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- Preparation method of [3-14C] marked 17alpha-estradiol
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The invention belongs to the technical field of synthesis of compounds marked by radioisotope 14C, and provides a preparation method of [3-14C] marked 17alpha-estradiol. The preparation method includes the following steps that 17beta-acylated elollactone and 14C marked acetylchloride serve as starting materials, and a condensation reaction, a primary hydrolysis reaction, a Mitsunobu reaction, an aromatization reaction and a secondary hydrolysis reaction are carried out to obtain [3-14C] marked 17alpha-estradiol. The method has the advantages that the synthesis cost is low, the line is short and the product yield is high. Besides, the preparation method is easy to operate and suitable for large-scale production.
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Paragraph 0089; 0104-0107
(2019/06/07)
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- Catalytic properties of pristine and defect-engineered Zr-MOF-808 metal organic frameworks
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Various defect-engineered Zr-trimesate MOF-808 compounds (DE-MOF-808) have been prepared by mixing the tricarboxylate ligands with dicarboxylate ligands; viz. isophthalate, pyridine-3,5-dicarboxylate, 5-hydroxy-isophthalate, or 5-amino-isophthalate. The resulting mixed-ligand compounds, MOF-808-X (X = IP, Pydc, OH or NH2) were all found to be highly crystalline and isostructural to the unmodified MOF-808. Pristine MOF-808 showed better catalytic performance than a UiO-66 reference compound for the Meerwein-Ponndorf-Verley (MPV) reduction of carbonyl compounds. This was attributed to a higher availability of coordinatively unsaturated Zr4+ sites (cus) in MOF-808 upon removal of formate ions. Meanwhile, cus in UiO-66 are only located at defect sites and are thus much less abundant. Further improvement of the catalytic activity of defect-engineered MOF-808-IP and MOF-808-Pydc was observed, which may be related with the occurrence of less crowded Zr4+ sites in DE-MOF-808. The wider pore structure of MOF-808 with respect to UiO-66 compounds translates into a sharp improvement of the activity for the MPV reduction of bulky substrates, as shown for estrone reduction to estradiol. Interestingly, MOF-808 produces a notable diastereoselectivity towards the elusive 17-α-hydroxy estradiol.
- Mautschke,Drache,Senkovska,Kaskel,Llabrés Xamena
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p. 3610 - 3616
(2018/07/29)
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- Application of in Situ FTIR for the Preparation of 17-α-Estradiol via Mitsunobu Reaction
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An efficient synthesis of 17-α-estradiol 1 is described. Utilization of in situ IR allowed for an online monitoring of the key Mitsunobu reaction and development of a safe and reliable synthesis of 17-α-estradiol 1 in 78% overall yield over three steps. Benzoylation of 17-β-estradiol 2 is conducted at high regioselectivity under phase-transfer catalysis (PTC) conditions, followed by a Mitsunobu reaction to invert the chiral center at C-17 and provide intermediate 5, containing the core structure of 17-α-estradiol 1. Finally, the desired active pharmaceutical ingredient (API) is prepared by saponification of the remaining esters.
- Cardoso, Flávio S. P.,Mickle, Gregory E.,Da Silva, Marco A.,Baraldi, Patricia T.,Ferreira, Fabio B.
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p. 306 - 311
(2016/03/04)
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- Thermodynamic Meerwein-Ponndorf-Verley reduction in the diastereoselective synthesis of 17α-estradiol
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The synthesis of 17α-hydroxy steroids generally requires multiple synthetic manipulations. The synthesis of 17α-estradiol is no exception, as this process involves the protection and release of the 3-hydroxy functional group. The diastereoselective reduction of the 17-keto-steroid can be utilized to prepare 17α-hydroxy-steroids. Here, 17α-estradiol was synthesized from commercially available estrone under thermodynamic Meerwein-Ponndorf-Verley (MPV) conditions in a single step, followed by simple chromatographic separation over silica gel. The remaining mixture of unreacted estrone and estradiols was easily recycled through Oppenauer oxidation to estrone, with an overall yield of 68% 17α-estradiol.
- Ahmed, Gulzar,Nickisch, Klaus
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- DNA-templated release of functional molecules with an azide-reduction- triggered immolative linker
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Nucleic acid templated reactions have attracted significant attention for nucleic acid sensing. Herein we report a general design which extends the potential of nucleic acid templated reactions to unleash the function of a broad diversity of small molecules such as a transcription factor agonist, a cytotoxic or a fluorophore.
- Gorska, Katarzyna,Manicardi, Alex,Barluenga, Sofia,Winssinger, Nicolas
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supporting information; scheme or table
p. 4364 - 4366
(2011/06/19)
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- Pharmaceutical composition with tumor necrosis factor A and 2-methoxyestrone-3-0-sulphamate for inhibition of estrone sulphatase
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A composition is described. The composition comprises i) a compound comprising a sulphamate group (“a sulphamate compound”); and ii) a biological response modifier.
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- Compound
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Disclosed and claimed are compounds suitable for use as an inhibitor of oestrone sulphatase in a subject in need thereof, as well as compositions containing such compounds and methods for using such compounds. Such compounds can be a sulphamate compound that has the Formula (X) and wherein X is a sulphamate group, and Y is CH2 and optionally any other H attached directly to the ring system is substituted by another group
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- Halogenated sulphamate-, phosphonate-, thiophosphonate-, sulphonate- and sulphonamide- compounds as inhibitors of steroid sulphatase
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A compound is described. The compound has the formula (Ia) as presented in the FIG. 1; wherein: X is a ring having at least 4 atoms in the ring; K is hydrocarbyl group; Rh1 is an optional halo group; Rh2 is an optional halo group; at least one of Rh1 and Rh2 is present; Rs is any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group. The compound is capable of inhibiting steroid sulphatase (STS) activity.
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- 17-Aryl linker derivatised estrogen 3-sulphamates as inhibitors of steroid sulphatase
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There is provided a compound comprising a steroidal ring system and a group R1 selected from any one of a sulphamate group, a phosphonate group, a thiophosphonate group, a sulphonate group or a sulphonamide group; wherein the D ring of the steroidal ring system is substituted by a group R2 of the formula —L—R3, wherein L is an optional linker group and R3 is an aromatic hydrocarbyl group.
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- OXIME-GROUP CONTAINING OESTRONE SULPHATASE INHIBITORS
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A sulphamate compound suitable for use as an inhibitor of oestrone sulphatase (E.C.3.1.6.2) is described. The compound is a polycyclic compound comprising at least two ring components, wherein the polycyclic compound comprises at least one sulphamate group attached to at least one of the ring components, and wherein at least one oxime group is attached to or is part of at least one of the ring components.
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- Composition
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There is provided a pharmaceutical composition comprising (i) a compound of the formula wherein: X is a hydrocarbyl ring having at least 4 atoms in the ring; K is a hydrocarbyl group; Rs is a sulphamate group; (ii) optionally admixed with a pharmaceutically acceptable carrier, diluent, excipient or adjuvant, wherein the compound is present in an amount to provide a dosage of no greater than 200 μg/day.
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- Use
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There is provided use of a material selected from (i) microtubule stabilizing agent; (ii) microtubule disrupter; (iii) a compound of the formula A-B wherein A is an oxyhydrocarbyl group and B is a cyclic group; and (iv) a compound of the formula C-D wherein C is an sulphamate group and D is a cyclic group, for the manufacture of a medicament for the inhibition of tumor necrosis factor α (TNFα) stimulated aromatase activity.
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- Composition
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There is provided a pharmaceutical composition comprising (i) a compound of the formula wherein: X is a hydrocarbyl ring having at least 4 atoms in the ring; K is a hydrocarbyl group; Rs is a sulphamate group; (ii) optionally admixed with a pharmaceutically acceptable carrier, diluent, excipient or adjuvant, wherein the compound is present in an amount to provide a dosage of no greater than 200 μg/day.
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- STEROID SULPHATASE INHIBITORS
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Steroid sulphatase inhibitors and pharmaceutical compositions containing them for use in the treatment of oestrone dependent tumors, especially breast cancer. The steroid sulphatase inhibitors are sulphonate and phosphonate esters of formula (I), where R is alkyl, alkenyl, cycloalkyl or aryl; X is P or S; Y is OH when X is P, and O when X is S; and -O- polycycle represents the residue of a polycyclic alcohol such as a sterol, preferably a 3-sterol
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- A Total Synthesis of Estradiol and its 6,6-Dimethyl Analogue
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A short, stereoselective synthesis of estradiol, and its 6,6-dimethyl analogue, was accomplished from non-steroidal starting materials.A key feature was the use of a benzothiophene unit to effect (i) the stereoselective formation of the required 8β-H c
- Collins, Mark A.,Jones, D. Neville
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p. 4467 - 4470
(2007/10/02)
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- Steroid sulphatase inhibitors
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The present invention provides pharmaceutical preparations for the treatment of estrogen dependent tumors. The pharmaceutical preparations contain an effective amount of a steroid sulphatase inhibitor of the formula: STR1 where R is alkyl, preferably C 1 -C 6 alkyl, and the ring system A B C D is a steroid nucleus selected from the group consisting of oestrone, dehydroepiandrosterone, substituted oestrones and substituted dehydroepiandrosterones or pharmaceutically acceptable salts thereof.
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- Stereoselective Introduction of Hydroxyl Groups via Hydrazones
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Reduction of tosylhydrazones by hydride reagents in wet alcohol gave predominantly alcohols whose stereochemistries are opposite to those of the major reduction products of the corresponding ketones with sodium borohydride.
- Tada, Masahiro,Chiba, Kazuhiro,Izumiya, Koji,Tamura, Mihoko
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p. 3532 - 3533
(2007/10/02)
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- Homogeneous and heterogeneous catalytic asymmetric reactions II. Asymmetric hydrogenation of steroid ketones
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The asymmetric reduction of steroid 17- and 20-ketones with chiral hydrosilanerhodium-(+)-and (-)-diop-complex catalysts allows different stereoselectivities in the formation of 17-alcohols, but not of 20-alcohols.The degree of this stereoselectivity is higher than that attained with other methods.The stereoselectivity can be explained in terms of the most preferred conformation of the α-siloxysteroid-rhodium intermediate complexes.
- Goendoes, Gyoergy,Gera, Lajos,Bartok, Mihaly,Orr, James C.
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p. 365 - 376
(2007/10/02)
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- Reduction of Steroid 17-Ketones by Enantiomeric Chiral Reducing Agents
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The reduction of steroid 17-ketones by a chiral hydrosilane-rhodium-(-)(2S,3S)-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane reagent allows greater stereoselectivity of 17α-alcohol formation than is obtained by other methods.
- Goendoes, Gyoergy,Orr, James C.
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p. 1238 - 1239
(2007/10/02)
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- Steroid ether splitting
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Ethers of aromatic steroids are cleaved to regenerate the hydroxy group with aluminum hydride, dialkylaluminum hydride or trialkylaluminum.
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