Synthesis and Pharmacology of Anti-Inflammatory Steroidal Antedrugs

Khan, Madeeha; Lee, Henry J.

doi:10.1021/cr068203e

Cited by 80 publications

(26 citation statements)

References 98 publications

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“…Development of novel anti-cancer drugs and therapies is always the basic mission for all medicinal chemists. Among the important natural organic compounds occurring in the animals, plants and fungi, steroids have been reported to possess great therapeutic value as antitumor, 1,2 anti-inflammatory, 3,4 and immunostimulant agents. 5 The natural steroidal skeleton has been therefore developed as original anticancer drug candidates, for example, the notable of Withaferin A 6,7 and oxysterols.…”

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confidence: 99%

“…20 Flash column chromatography was used to remove most of dark hydroquinone, and trienone 2 was obtained in 83% yield after standard column chromatography. When exploring the ring-opening reaction of monoepoxide 3 with nucleophilic alcohols (R 1 OH), we found that the reaction could not be catalyzed by strong acids in various solvents, such as 1 mol/L HCl in CH 3 Furthermore, no catalyst or using strong base catalyst in aqueous solvent also resulted in the unreacted starting material. To our surprise, the monoepoxide 3 could be smoothly converted to 2-alkyloxyl substituted (25R)-spirostan-1,4,6-triene-3-ones 4 under catalytic amount of NaOH in anhydrous alcohol (Scheme 1).…”

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Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and ‘click’ strategy

Yang

Huang

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and ‘click’ strategy

Yang

Huang

et al. 2015

Bioorganic & Medicinal Chemistry Letters

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“…These molecules represent broadly useful starting materials for complex molecule synthesis, and the basic structural framework is present in a wide range of medicinally relevant molecules. [3] Despite the importance of these structures, surprisingly few direct methods are available to selectively functionalize the arene nucleus in the absence of other groups: aromatic substitution reactions require directing functionality to control reactivity and selectivity; cross coupling processes need pre-installed functional groups; and while the acidity of the CÀH bonds between the arene and carbonyl groups facilitates a wealth of enolate chemistry, it precludes the use of directed ortho-lithiation reactions. [4] A potential solution to some of these limitations has recently been presented through the development of orthoselective Pd II -catalyzed C À H bond functionalization reactions.…”

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Copper(II)‐Catalyzed meta‐Selective Direct Arylation of α‐Aryl Carbonyl Compounds

et al. 2010

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Substituted arenes dominate the properties of many natural products, medicines, and materials.[1] Therefore, the development of new methods for direct and selective aromatic functionalization is a persistent challenge for synthetic chemists.[2] A particularly important class of substituted aromatic compounds is the a-aryl carbonyl structure. These molecules represent broadly useful starting materials for complex molecule synthesis, and the basic structural framework is present in a wide range of medicinally relevant molecules.[3] Despite the importance of these structures, surprisingly few direct methods are available to selectively functionalize the arene nucleus in the absence of other groups: aromatic substitution reactions require directing functionality to control reactivity and selectivity; cross coupling processes need pre-installed functional groups; and while the acidity of the CÀH bonds between the arene and carbonyl groups facilitates a wealth of enolate chemistry, it precludes the use of directed ortho-lithiation reactions. [4] A potential solution to some of these limitations has recently been presented through the development of orthoselective Pd II -catalyzed C À H bond functionalization reactions. [5,6] The cyclometalation strategy employed in these transformations, however, cannot be used to facilitate metaor para-functionalization of these molecules due to restrictive geometric constraints. [7,8] The synthetic utility of the generic a-aryl acetic acid motif would be significantly expanded by a methodology that provides direct access to isomeric molecules of potentially beneficial therapeutic value (Scheme 1 A). Herein, we report a copper-catalyzed meta-selective arylation of the a-aryl carbonyl scaffold with diaryliodonium salts that is directed by a remote and versatile Weinreb amide group (Scheme 1 B). This method provides a novel synthetic route to arenes displaying diverse substitution, benzylic chirality and quaternary centers. Its potential is further enhanced through its compatibility with iterative C À H bond functionalization methods that will have broad utility in the synthesis of highly functionalized arenes.As part of our studies towards meta-selective functionalization processes, [8d] we postulated that the location of a carbonyl group plays a key role in determining the selectivity of our Cu II -catalyzed meta-arylation of pivanilides. To test this hypothesis, we speculated that the a-aryl carbonyl would also provide a similar reactivity platform because the carbonyl motif is displayed in a similar position relative to the arene nucleus. Notably, the arene nucleophilicity of the electronically neutral a-aryl carbonyl motif is drastically different to the electron-rich pivanilide.To test whether a-aryl carbonyl compounds could be functionalized at the meta-position, we prepared diethylamide 1 a and treated it with diphenyliodonium triflate and 20 mol % Cu(OTf) 2 in dichloroethane at 70 8C, conditions that are identical to those used for the arylation of pivanilides.[8d]After reacti...

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“…Natural steroids with desired biological properties have been used in pharmaceutical chemistry [2] and, to eliminate undesired effects, their structure has been modified. Also, synthetic analogues of natural steroids with desired pharmacological properties are constantly being produced and investigated [2,3].…”

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confidence: 99%

A ring conformation of androstan-3-one

Sroka

Majerz

2016

Molecular Physics

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For solid-state structures of androstan-3-one derivatives presented in Cambridge structural database (CSD), the puckering parameters for the six-membered rings were calculated to investigate the ring conformation. It was found that for the A-ring, except for typical chair conformation, the boat conformation appears very often. This conformation is also possible for the rings B and C. There are a few compounds with boat conformation of A-and B-or A-and C-ring, but simultaneous boat conformation of B-and C-ring has not been found. The methyl substituents at 10 and 13 position of the androstane-3-one as well as carbonyl group at the 3-carbon atom play a significant role in the stabilisation of the structure of androstan-3-one.

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Synthesis and Pharmacology of Anti-Inflammatory Steroidal Antedrugs

Cited by 80 publications

References 98 publications

Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and ‘click’ strategy

Synthesis and cytotoxic activities of 2-substituted (25R)-spirostan-1,4,6-triene-3-ones via ring-opening/elimination and ‘click’ strategy

Copper(II)‐Catalyzed meta‐Selective Direct Arylation of α‐Aryl Carbonyl Compounds

A ring conformation of androstan-3-one

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