Synthesis of Transition-Metal Steroid Derivatives

Bideau, Franck Le; Dagorne, Samuel

doi:10.1021/cr400269j

Cited by 43 publications

(38 citation statements)

References 361 publications

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“…Structures eight titanocene steroid conjugates (26)(27)(28)(29)(30)(31)(32)(33) have been synthesized and structures have been characterized. [8,10,[44][45][46] The anti-proliferative activity of (26)(27)(28)(29)(30)(31)(32)(33) was determined in colon cancer HT29 and breast cancer MCF-7 cell lines. Titanocenyl containing cholesterol rings with IC 50 values over 200 μM, with the exception of complex (30) and highly active titanocenyls containing sex steroids with IC 50 values below 50 μM on MCF-7 cell line were reported.…”

Section: Titanocene Steroid Conjugatesmentioning

confidence: 99%

“…Titanocenyl containing cholesterol rings with IC 50 values over 200 μM, with the exception of complex (30) and highly active titanocenyls containing sex steroids with IC 50 values below 50 μM on MCF-7 cell line were reported. [10,46] It should be pointed out that the higher cytotoxic complexes are those containing sex steroid derivatives whereas those including cholesterol unit (30, 31 and 32) showed less cytotoxicity. [8,[47][48][49] Antineoplastic (0.996); Antieczematic (0.760); Antipruritic (0.700); Antihypercholesterolemic (0.662); Antineoplastic, alkylator (0.642); Antipruritic, allergic (0.613); Prostate disorders treatment (0.605); Immunosuppressant (0.572); Biliary tract disorders treatment (0.570); Cholesterol synthesis inhibitor (0.568); Antipsoriatic (0.545); Anesthetic general (0.538); Hypolipemic (0.530)…”

Section: Titanocene Steroid Conjugatesmentioning

confidence: 99%

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Ferrocene and titanocene steroid conjugates: Structures and activities – a brief review

Dembitsky

Gloriozova

Imbs

2018

Vietnam Journal of Chemistry

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The present review describes the biological activities of ferrocenes and titanocenes steroid conjugates. Ferrocenes steroid conjugates demonstrate antineoplastic and antihypercholesterolemic activity with a confidence more than 90 percent, and can be used as erythropoiesis‐stimulating agents. Titanocenes steroid conjugates show anti‐inflammatory and anti‐seborrheic activity with a confidence more than 70 percent, and can also be used as glutaconyl‐CoA decarboxylase inhibitors and/or erythropoiesis‐stimulating agents. With the computer programme PASS and based on structure–activity relationships (SAR), some additional activities are also predicted, which point towards new possible applications of these lipids. This review is devoted to synthetic lipids ferrocenes and titanocenes steroid conjugates and their biological activity, which are of great interest for medicine, as well as for pharmacologists and the pharmaceutical industry.

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Section: Titanocene Steroid Conjugatesmentioning

confidence: 99%

Section: Titanocene Steroid Conjugatesmentioning

confidence: 99%

Ferrocene and titanocene steroid conjugates: Structures and activities – a brief review

Dembitsky

Gloriozova

Imbs

2018

Vietnam Journal of Chemistry

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“…Ferrocifen showed excellent antiproliferative activity on MCF-7, and docking studies on ERα revealed that its activity is due to the antiestrogenic properties it elicits from the receptor [12]. There are more recent precedents of titanocenes and half-titanocenes with enhanced antiproliferative activity on the MCF-7 cell line, particularly some of them with IC 50 values in the micromolar range [14][15][16]. However, the mechanistic aspects of these species have not been thoroughly explored.…”

Section: Introductionmentioning

confidence: 99%

Steroid-Functionalized Titanocenes: Docking Studies with Estrogen Receptor Alpha

et al. 2016

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Estrogen receptor alpha (ERα) is a transcription factor that is activated by hormones, with 17β-estradiol being its most active agonist endogenous ligand. ERα is also activated or inactivated by exogenous ligands. ER is overexpressed in hormone-dependent breast cancer, and one of the treatments for this type of cancer is the use of an ER antagonist to halt cell proliferation. We have previously reported four steroid-functionalized titanocenes: pregnenolone, dehydroepiandrosterone (DHEA), trans-androsterone, and androsterone. These steroids have hormonal activity as well as moderate antiproliferative activity, thus these steroids could act as vectors for the titanocene dichloride to target hormone-dependent cancers. Also, these steroids could increase the antiproliferative activity of the resulting titanocenes based on synergism. In order to elucidate which factors contribute to the enhanced antiproliferative activity of these steroid-functionalized titanocenes, we performed docking studies between ERα and the titanocenes and the steroids. The binding affinities and type of bonding interactions of the steroid-functionalized titanocenes with ERα are herein discussed.

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“…[1] For example, kaurene [2] is the biosynthetic precursor of the plant hormones gibberellins, boldenone [3] is an anabolic steroid, totaradiol [4a-d] is a diterpene natural product that exhibits good antimicrobial properties, and triptoquinone B exhibits a remarkable inhibitory activity against interleukin-1 release. [4e-f] Their syntheses have attracted a great deal of attention with the emergence of various excellent methods.…”

mentioning

confidence: 99%

“…[16a] The method was also applied to the construction of the skeleton of the anabolic steroid boldenone (Scheme 2). [3] Thus, ketal 9, [18] which was readily prepared from the Hajos-Parrish ketone, was reacted with bromide 10 in the presence of NaH to form 11 in an unoptimized yield of 17 %. Conversion of 11 into the vinyl triflate with Tf 2 O as the reagent followed by treatment with BBr 3 provided 12 in 70 % overall yield.…”

mentioning

confidence: 99%

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

Guo

Chen

et al. 2015

Angewandte Chemie

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A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (À)-totaradiol.Tricyclic skeletons bearing chiral all-carbon quaternary centers, such as chiral phenanthrenone derivatives, exist in numerous complex terpenes and steroids with interesting biological activities ( Figure 1). [1] For example, kaurene [2] is the biosynthetic precursor of the plant hormones gibberellins, boldenone [3] is an anabolic steroid, totaradiol [4a-d] is a diterpene natural product that exhibits good antimicrobial properties, and triptoquinone B exhibits a remarkable inhibitory activity against interleukin-1 release. [4e-f] Their syntheses have attracted a great deal of attention with the emergence of various excellent methods. [5] Among them, the asymmetric intramolecular Heck reaction [6] has become a powerful method for constructing chiral polycyclic skeletons bearing all-carbon quaternary centers ( Figure 2). However, a number of synthetic steps are often required either in constructing the olefin moiety necessary for the Heck cyclization or for the post-modification of the Heck product to the target molecule. Alternatively, asymmetric intramolecular dearomative cyclizations [7,8] between two aryl systems can offer better synthetic efficiency owing to the availability of aryl systems as well as the convenience in the post-modification of the cyclization product. Herein, we present a powerful asymmetric palladium-catalyzed dearomative cyclization that has led to a series of chiral phenanthrenone derivatives bearing an allcarbon quaternary center in excellent enantioselectivities. The new method has been successfully applied in the highly efficient synthesis of a chiral kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and an enantioselective total synthesis of the diterpene natural product (À)-totaradiol.Although dearomative cyclizations have been frequently applied in natural product synthesis, the asymmetric transition-metal-catalyzed dearomative cyclization has remained underdeveloped, and only a few examples of efficient intramolecular dearomative arylations have been reported thanks to the pioneering work from the Buchwald, [9] Bedford, [10] and You [11] groups. Buchwald [9] and co-workers developed efficient dearomative cyclizations to form chiral benzocarbazole derivatives and spirocyclohexadienones bearing all-carbon quaternary centers. You [11e] et al. recently reported an interesting dearomative cyclization to form a tetracyclic spiroamine framework. However, to the best of our knowledge, enantioselective dearomative...

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Synthesis of Transition-Metal Steroid Derivatives

Cited by 43 publications

References 361 publications

Ferrocene and titanocene steroid conjugates: Structures and activities – a brief review

Ferrocene and titanocene steroid conjugates: Structures and activities – a brief review

Steroid-Functionalized Titanocenes: Docking Studies with Estrogen Receptor Alpha

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

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