- An easy deoxygenation of conjugated epoxides
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An easy and high yielding transformation of epoxyketones and phenyl substituted epoxides to trans olefins in a convergent diastereoselective process is reported. The method was applied to the selective C-25 hydroxy- functionalisation of 3-keio-Δ4-cholestan-3-one, a key intermediate for the synthesis of C-25 hydroxy vitamin D3. (C) 2000 Elsevier Science Ltd.
- Righi, Giuliana,Bovicelli, Paolo,Sperandio, Anna
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- Design, synthesis and biochemical studies of new 7α-allylandrostanes as aromatase inhibitors
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Two series of derivatives of 7α-allylandrostenedione, namely its 3-deoxo and 1-ene analogs, were designed and synthesised and their biochemical activity towards aromatase evaluated. In each of these series, the C-17 carbonyl group was further replaced by the hydroxyl and acetoxyl groups. The attained data pointed out that the absence of the C-3 carbonyl group led to a slightly decrease in the inhibitory activity and the introduction of an additional double bond in C-1 revealed to be a very beneficial structural change in the studied compounds (compound 12, IC50 = 0.47 μM, Ki = 45.00 nM). Furthermore, the relevance of the C-17 carbonyl group in the D-ring as a structural feature required to achieve maximum aromatase inhibitory activity is also observed for this set of derivatives.
- Varela, Carla L.,Amaral, Cristina,Correia-Da-Silva, Georgina,Carvalho, Rui A.,Teixeira, Natércia A.,Costa, Saul C.,Roleira, Fernanda M.F.,Tavares-Da-Silva, Elisiário J.
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- Synthesis and preliminary in vitro biological evaluation of 7α-testosterone-chlorambucil hybrid designed for the treatment of prostate cancer
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The synthesis of 7α-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7α-allyltestosterone with 35% overall yield. MTT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP (AR+)) and shows similar activity than the parent drug, chlorambucil. Thus, the new hybrid shows promising potential for drug targeting of hormone-dependent prostate cancer through its capacity of delivering chlorambucil directly to the site of treatment. This could extend the use of chlorambucil to prostate cancer in the future.
- Bastien, Dominic,Hanna, Rana,Leblanc, Valérie,Asselin, éric,Bérubé, Gervais
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- Synthesis and characterization of dimeric steroids based on 5-oxo-4,5-seco-yne units linked by a diyne spacer
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New dimeric steroids in which two 5-oxo-4,5-seco-3-yne steroids units are linked by a flexible diyne spacer, were prepared by both Eglinton and Pd-catalyzed coupling of the corresponding monomers. X-Ray crystallography shows that one of the obtained dimers displays a novel supramolecular network in which the facial hydrophobicity of the steroidal skeleton plays an important role. The crystal packing is dominated by interactions that accommodate the steroid cores in a highly crowded packed columnar self-assembly. Unambiguous NMR characterization of the obtained compounds is also provided.
- Valdez-García, Ricardo M.,Alarcón-Manjarrez, Carlos,Arcos-Ramos, Rafael,Flores-álamo, Marcos,Iglesias-Arteaga, Martín A.
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- Aspects of the progesterone response in Hortaea werneckii: Steroid detoxification, protein induction and remodelling of the cell wall
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Progesterone in sublethal concentrations temporarily inhibits growth of Hortaea werneckii. This study investigates some of the compensatory mechanisms which are activated in the presence of progesterone and are most probably contributing to escape from growth inhibition. These mechanisms lead on the one hand to progesterone biotransformation/detoxification but, on the other, are suggested to increase the resistance of H. werneckii to the steroid. Biotransformation can detoxify progesterone efficiently in the early logarithmic phase, with mostly inducible steroid transforming enzymes, while progesterone biotransformation/detoxification in the late logarithmic and stationary phases of growth is not very efficient. The relative contribution of constitutive steroid transforming enzymes to progesterone biotransformation is increased in these latter phases of growth. In the presence of progesterone, activation of the cell wall integrity pathway is suggested by the overexpression of Pck2 which was detected in the stationary as well as the logarithmic phase of growth of the yeast. Progesterone treated H. werneckii cells were found to be more resistant to cell lysis than mock treated cells, indicating for the first time changes in the yeast cell wall as a result of treatment with progesterone.
- Krizancic Bombek, Lidija,Lapornik, Ajda,Ukmar, Marjeta,Matis, Maja,Cresnar, Bronislava,Katalinic, Jasna Peter,Zakelj-Mavric, Marija
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- TRANSFORMATION OF ANDROSTANE DERIVATIVES BY SPIRODELA OLIGORRHIZA
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Spirodela oligorrhiza (duckweed) of transforming some steroids of the androstane series.Hydrolysis of the acetates of testosterone and of 3-β-hydroxyandrost-5-en-17-one by this species yielded the corresponding alcohols.Further transformation of testosterone and reduction of androst-4-ene-3,17-dione indicated the interconversions of the hyroxy-ketone function on C-17 and redution of the Δ4-double bond to the trans-A/B system.Only a trace amount of 3β-hydroxyandrost-5-en-17-one underwent further transformations.
- Tlomak, Elzbieta,Pawlowicz, Pawel,Czerwinski, Witold,Siewinski, Antoni
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- HYDROXYLATION OF PROGESTERONE BY CEPHALOSPORIUM APHIDICOLA
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The fungus, Cephalosporium aphidicola, has been shown to hydroxylate progesterone predominantly at the 6β- and 11α-positions.Minor metabolites include tetstosterone acetate, the 20(R)-alcohol and 12β,17α-dihydroxyprogesterone.The sequence involves hydroxylation at 11α and then 6β.The hydroxylations of 11α- and 17α-hydroxyprogesterone and 9β,10α-retroprogesterone have also been examined in the light of these results. - Key words: Cephalosporium aphidicola; progesterone; 9β,10α-retroprogesterone; steroid; microbiological hydroxylation.
- Farooq, Afgan,Hanson, James R.,Iqbal, Zahida
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- Highly efficient, solvent-free esterification of testosterone promoted by a recyclable polymer-supported tosylic acid catalyst under microwave irradiation
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Although the classical acylation of testosterone clearly benefits from a broad substrate scope and available catalysts, the requirement of hazardous reagents and the high waste production are its drawbacks. To optimize the process efficiency as well as minimize the environmental impact, we decided to develop a novel method of testosterone esters synthesis, which relies on the usage of recyclable heterogeneous polymer-supported tosylic acid catalyst and microwave-assistance effect in a non-solvent system. Under the established MW-conditions, the acceleration of the process rate was so efficient that the reaction completed within 2.5 min, thus affording the desired esters in the 33–96% yield range without using a work-up procedure. Furthermore, the elaborated catalytic system could be recycled for at least 2 runs not only without a loss of the products yield, but unexpectedly with significant improvement of the reaction efficiency, which may indicate that the reduction of the catalyst loading is possible. We believe that this finding constitutes a very good starting-point for further optimization of the studied process.
- Borowiecki, Pawe?,Kraszewski, Maciej
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- Synthesis and evaluation of new steroidal lactam conjugates with aniline mustards as potential antileukemic therapeutics
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Alkylating agents are still nowadays one of the most important classes of cytotoxic drugs, which display a wide range of therapeutic use for the treatment of various cancers. We have synthesized and tested four hybrid homo-azasteroidal alkylating esters for antileukemic activity against five sensitive to alkylating agents human leukemia cell lines in vitro and against P388 murine leukemia in vivo. Comparatively, melphalan and 3-(4-(bis(2-chloroethyl)amino)phenoxy)propanoic acid (POPAM) were also examined. All the homo-aza-steroidal alkylators showed relatively lower acute toxicity, very promising and antileukemic activity both in vitro and in vivo.
- Trafalis, Dimitrios,Geromichalou, Elena,Dalezis, Panagiotis,Nikoleousakos, Nikolaos,Sarli, Vasiliki
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- Novel catalytic activity of immobilized spores under reduced water activity
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Onset of a new catalytic function during transformation of progesterone by immobilized spores of Aspergillus ochraceus TS under reduced water activity is reported. The pathway of transformation, which furnished 1,4-androstadien-17β-ol-3-one and 1,4-androstadien-3,17-dione due to cleavage of C17-C20 bond, is different from normal reaction sequence.
- Dutta, Tapan K.,Samanta, Timir B.
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- Diastereoselective hydroformylation of Δ4-steroids with rhodium-phosphite catalysts
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The hydroformylation of two steroidal substrates, namely 17β-acetoxyandrost-4-ene 1 and 3β,17β-diacetoxyandrost-4-ene 2, with a rhodium tris(O-tert-butylphenyl)phosphite catalyst was investigated. In both cases, the major reaction product was 4β-formyl-17β-acetoxy-5β-androstane 3, which was isolated and characterized by X-ray diffraction and NMR techniques. This reaction is the first example of catalytic carbonylation to the β face of a steroid backbone. The effect of reaction temperature, the pressure at which the reaction was completed and the ligand:Rh ratio on the regio- and stereoselectivity of the reaction is also discussed.
- Freixa, Zoraida,Pereira, Mariette M.,Bayon,Silva, Artur M.S.,Salvador, Jorge A.R.,Beja, Ana Matos,Paixao, Jose A.,Ramos, Manuela
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- Iridium-catalysed highly selective reduction-elimination of steroidal 4-en-3-ones to 3,5-dienes in water
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Steroidal 3,5-diene is an important structural motif in steroid drugs. In this report, an iridium-catalyzed reduction-elimination of readily available steroidal 4-en-3-ones is realized to prepare steroidal 3,5-dienes. At a low catalyst loading (S/C = 200), heating 4-en-3-ones in a water-mixed organic solvent with formic acid without inert atmosphere protection afforded the desired 3,5-dienes in moderate to excellent yields. In a gram-scale preparation, recrystallization is used instead of column chromatography to purify products. Excellent functionality tolerance and regioselectivity are featured. Structural moieties such as alkanols (primary, secondary and tertiary), esters (except for formate), tolylates, and ketones (endocyclic or exocyclic) are not affected. Surprisingly, the reduction-elimination only takes place at A-ring 4-en-3-ones. In addition, bicyclic 4-en-3-ones are also viable substrates. Synthetic applications of steroidal 3,5-dienes are demonstrated. Our method can also lead to steroidal 3,5-dienes-3-d (>99% d-incorporation) when DCO2D and D2O are used together.
- Li, Jide,Tang, Weiping,Ren, Demin,Xu, Jiaxi,Yang, Zhanhui
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supporting information
p. 2088 - 2094
(2019/04/29)
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- Selective reduction of 4,6- conjugate diene -3-one steroid compound method
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Belonging to the field of chemical pharmacy, the invention relates to a method for selective reduction of 4, 6-conjugated diene-3-one steroid, and solves the problem of low yield in hydrogen reduction. The method mainly includes the steps of: 1) adding the 4, 6-conjugated diene-3-one steroid, a liquid solvent, a catalyst, and a reducing agent hydrogen donor into a reaction kettle, performing nitrogen protection, and carrying out stirring heating till reflux; 2) carry out reflux reaction for 3-10h; 3) at the end of reaction, filtering out the catalyst; 4) distilling the solvent; 5) adding purified water after distillation; and 6) conducting cooling, pumping filtering, washing and drying to obtain a 4-ene-3-steroid crystal.
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Paragraph 0066-0073
(2019/11/21)
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- New testosterone derivatives as semi-synthetic anticancer agents against prostate cancer: Synthesis and preliminary biological evaluation
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Prostate cancer (PC) is a major health issue in the world. Treatments of localized PC are quite efficient and usually involve surgery, radiotherapy and/or hormonal therapy. Metastatic PC is however rarely curable to this day. Treatments of metastatic PC involve radiotherapy, chemotherapy and hormonal treatment such as orchiectomy, antiandrogens and luteinizing hormone-releasing hormone agonists. The suppression of tumor growth by hormonal treatment is efficient but overtime resistance still occurs and the disease progresses. Thus, more urgently than ever there is a need for discovery of new treatment options for castration-resistant PC (CRPC). Hence, we designed and tested a series of amide derivatives located at position 7α of testosterone as prospective natural or semisynthetic anticancer agents against CRPC with the goal of discovering therapeutic alternatives for the disease. This manuscript describes an efficient path towards the target molecules that are made in only 6 or 7 chemical steps from testosterone in good overall yields. This strategy can be used to make several compounds of interest that present higher biological activity than the classic antiandrogen; cyproterone acetate (3). The best testosterone-7α-amide was the N-2-pyridylethylamide (25) which was as active as the antiandrogen cyproterone acetate (3) on androgen-dependent LNCaP cells and 2.7 times more active on androgen-independent PC3 prostate cancer cells. The results obtained show the synthetic feasibility and the potential for future development of this unique class of semi-synthetic anticancer agents that offer the premise of new treatment modalities for patients afflicted with CRPC.
- Morin, Nathalie,Bruneau, Julie,Fortin, Sébastien,Brasseur, Kevin,Leblanc, Valérie,Asselin, Eric,Bérubé, Gervais
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p. 531 - 539
(2015/08/18)
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- TESTOSTERONE DERIVATIVES WITH A CARBOXYALKYL SUBSTITUTION IN POSITION 3 AND USE THEREOF FOR THE PRODUCTION OF LABELLED STEROIDS FOR DETERMINING THE CONCENTRATION OF TESTOSTERONE IN A BIOLOGICAL SAMPLE
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A testosterone derivative of formula (I): where n is an integer in a range of from 1 to 10, and Y represents an activated or ready-to-be-activated group allowing formation of an amide bond with a primary amine of a molecule. Conjugates including the testosterone derivatives and a marker, methods for determining the concentration of testosterone in a biological sample, and methods for preparing the testosterone derivatives are also provided.
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Paragraph 0169; 0170
(2015/11/23)
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- Insights into the synthesis of steroidal A-ring olefins
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The classical synthesis, followed by purification of the steroidal A-ring Δ1-olefin, 5α-androst-1-en-17-one (5), from the Δ1-3-keto enone, (5α,17β)-3-oxo-5-androst-1-en-17-yl acetate (1), through a strategy involving the reaction of Δ1- 3-hydroxy allylic alcohol, 3β-hydroxy-5α-androst-1-en-17β-yl acetate (2), with SOCl2, was revisited in order to prepare and biologically evaluate 5 as aromatase inhibitor for breast cancer treatment. Surprisingly, the followed strategy also afforded the isomeric Δ2-olefin 6 as a by-product, which could only be detected on the basis of NMR analysis. Optimization of the purification and detection procedures allowed us to reach 96% purity required for biological assays of compound 5. The same synthetic strategy was applied, using the Δ4-3-keto enone, 3-oxoandrost-4-en-17β-yl acetate (8), as starting material, to prepare the potent aromatase inhibitor Δ4-olefin, androst-4-en-17-one (15). Unexpectedly, a different aromatase inhibitor, the Δ3,5-diene, androst-3,5-dien-17-one (12), was formed. To overcome this drawback, another strategy was developed for the preparation of 15 from 8. The data now presented show the unequal reactivity of the two steroidal A-ring Δ1- and Δ4-3- hydroxy allylic alcohol intermediates, 3β-hydroxy-5α-androst-1-en- 17β-yl acetate (2) and 3β-hydroxyandrost-4-en-17β-yl acetate (9), towards SOCl2, and provides a new strategy for the preparation of the aromatase inhibitor 12. Additionally, a new pathway to prepare compound 15 was achieved, which avoids the formation of undesirable by-products. Copyright
- Varela, Carla L.,Roleira, Fernanda M. F.,Costa, Saul C. P.,Pinto, Alexandra S. C. T.,Martins, Ana I. O. S.,Carvalho, Rui A.,Teixeira, Natercia A.,Correia-Da-Silva, Georgina,Tavares-Da-Silva, Elisiario
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- New structure-activity relationships of A-and D-ring modified steroidal aromatase inhibitors: Design, synthesis, and biochemical evaluation
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A- and D-ring androstenedione derivatives were synthesized and tested for their abilities to inhibit aromatase. In one series, C-3 hydroxyl derivatives were studied leading to a very active compound, when the C-3 hydroxyl group assumes 3β stereochemistry (1, IC50 = 0.18 μM). In a second series, the influence of double bonds or epoxide functions in different positions along the A-ring was studied. Among epoxides, the 3,4-epoxide 15 showed the best activity (IC50 = 0.145 μM) revealing the possibility of the 3,4-oxiran oxygen resembling the C-3 carbonyl group of androstenedione. Among olefins, the 4,5-olefin 12 (IC50 = 0.135 μM) revealed the best activity, pointing out the importance of planarity in the A,B-ring junction near C-5. C-4 acetoxy and acetylsalicyloxy derivatives were also studied showing that bulky substituents in C-4 diminish the activity. In addition, IFD simulations helped to explain the recognition of the C-3 hydroxyl derivatives (1 and 2) as well as 15 within the enzyme.
- Varela, Carla,Tavares Da Silva, Elisiário J.,Amaral, Cristina,Correia Da Silva, Georgina,Baptista, Teresa,Alcaro, Stefano,Costa, Giosuè,Carvalho, Rui A.,Teixeira, Natércia A. A.,Roleira, Fernanda M. F.
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supporting information; experimental part
p. 3992 - 4002
(2012/07/30)
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- Using benzotriazole esters as a strategy in the esterification of tertiary alcohols
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Benzotriazole esters formed in situ were found to be efficient intermediates in the esterification of tertiary alcohols using 4-(dimethylamino)pyridine (DMAP) as the base. These mild and basic reaction conditions allow the conversion of various substrates into esters in good yield
- Morales-Serna, Jose Antonio,Vera, Aline,Paleo, Ehecatl,Garcia-Rios, Erendira,Gavino, Ruben,Garcia De La Mora, Gustavo,Cardenas, Jorge
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experimental part
p. 4261 - 4267
(2011/02/25)
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- A simple, general, and highly chemoselective acetylation of alcohols using ethyl acetate as the acetyl donor catalyzed by a tetranuclear zinc cluster
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In the presence of a Zn-cluster catalyst, alcohols are efficiently converted to the corresponding acetate just by refluxing in EtOAc. The mild reaction conditions enabled the reactions of various functionalized alcohols to proceed in good to excellent yield. Moreover, even when a large excess of the acetyl donor is used, the hydroxyl groups are selectively acetylated in the presence of highly nucleophilic aliphatic amino groups, approaching chemoselectivity to that of enzymatic system. Georg Thieme Verlag Stuttgart.
- Iwasaki, Takanori,Maegawa, Yusuke,Hayashi, Yukiko,Ohshima, Takashi,Mashima, Kazushi
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experimental part
p. 1659 - 1663
(2009/12/04)
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- Oxidation of Δ4- and δ5-steroids with hydrogen peroxide catalyzed by porphyrin complexes of MnIII and FeIII
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In this paper we describe a new environmentally friendly method to promote the stereoselective epoxidation of Δ4- and Δ5- steroids. Metalloporphyrins efficiently catalyze the epoxidation reactions of 17β-acetoxy-4-androstene (1), 4-cholestene (2) and 3β-acetoxy-5- cholestene (3) in the presence of H2O2 as oxygen donor. Modeling the molecular structure of the porphyrin as well as the central metal allows the control of the preferential formation of α- or β-epoxides. Porphyrins with bulky, electron-withdrawing groups in the ortho positions of the meso phenyls and with MnIII as the central metal ion, such as [Mn(TDCPP)Cl], gave preferentially the β-epoxide of Δ4- and Δ5-steroids. [Fe(TPFPP)Cl] catalyzes preferentially the α-epoxidation of Δ4-steroids and also increases the stereoselectivity for the α-epoxide in Δ5-steroids, similar to the results obtained with m-CPBA (m-chloroperbenzoic acid) as oxidant. The substrate structure strongly influences the chemoselectivity of the reactions. The X-ray structures of two main products were determined, and two-dimensional NMR techniques allowed the full assignment of 1H and 13C NMR resonances as well as the stereochemistry of these products. A mechanistic proposal involving oxo species for the β-approach and peroxy species for the α-approach is proposed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Rebelo, Susana L. H.,Simoes, Mario M. Q.,M. Graca P. M. S. Neves,Silva, Artur M. S.,Cavaleiro, Jose A. S.,Peixoto, Andreia F.,Pereira, Mariette M.,Silva, Manuela R.,Paixao, Jose A.,Beja, Ana M.
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p. 4778 - 4787
(2007/10/03)
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- Microwave induced selective enolization of steroidal ketones and efficient acetylation of sterols in semisolid state
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Under microwave irradiation steroidal enones, more specifically, position three carbonyls were efficiently and selectively converted to the corresponding enol acetates in the presence of additional enolizable carbonyl functions at other positions, using acetic anhydride and a catalytic amount of toluene-p-sulfonic acid. Acetylation of hydroxyl groups of the sterols, including those at the hindered positions, was near quantitative. Strictly anhydrous conditions were not a pre-requisite for acetylation and the reaction system easily tolerated up to 10% (v/v) moisture.
- Marwah, Padma,Marwah, Ashok,Lardy, Henry A.
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p. 2273 - 2287
(2007/10/03)
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- Lewis acid catalyzed acylation reactions: Scope and limitations
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Acylation of alcohols, thiols, and sugars were studied with a variety of Lewis acids, and it was found that Cu- and Sn(OTf)2 are very efficient in catalyzing the reaction under mild conditions. Among these two catalysts, Cu(OTf)2 was preferred because of its lower cost and relatively higher yield of the acylated product. The reaction was studied in several solvents, but CH2Cl2 was preferred. It was also observed that the present method is suitable for acylation of tertiary alcohols. Sugars were also acylated without any epimerization at the anomeric center. It is further shown here that this method is also suitable for selective acylation of primary or secondary alcohols over tertiary ones.
- Chandra, Kusum L,Saravanan,Singh, Rajesh K,Singh, Vinod K
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p. 1369 - 1374
(2007/10/03)
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- KF-Al2O3 is an efficient solid support reagent for the acetylation of amines, alcohols, and phenols. Impeding effect of solvent on the reaction rate
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KF-Al2O3 brings about rapid acetylation of a range of amines, alcohols, and phenols with Ac2O/AcCl. Aliphatic alcohols are acetylated chemoselectively in the presence of phenols. 1° alcohols react several times faster than 2° alcohols. 3° alcohols do not react.
- Yadav, Veejendra K,Ganesh Babu,Mittal, Manish
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p. 7047 - 7051
(2007/10/03)
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- One-step conversion of silyl/THP ethers into the corresponding acetates
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A variety of silyl and THP ethers were directly converted into the corresponding acetates using acetic anhydride in the presence of a catalytic amount of Cu(OTf)2 in CH2Cl2. It was observed that MEM ethers could also be cl
- Chandra, Kusum L,Saravanan, P,Singh, Vinod K
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p. 5309 - 5311
(2007/10/03)
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- The allylic oxidation of unsaturated steroids by tert-butyl hydroperoxide using homogeneous and heterogeneous cobalt acetate
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Cobalt acetate is an effective catalyst for the selective allylic oxidation of unsaturated steroids using tert-butyl hydroperoxide especially when used in a supported form when it can be easily recovered and reused.
- Salvador,Clark
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- The Reaction of 3,4-Epoxy-5-hydroxyandrostanes with Hydrobromic Acid
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The formation of aromatic and ketonic products from the treatment of 17β-acetoxy-3α,4α-epoxy-5α-hydroxyandrostane and its 3β,4β-epoxy-5β-hydroxy isomer with hydrobromic acid in glacial acetic acid is discussed in the context of the diaxial and diequatorial opening of the epoxide.
- Baldwin, Derek,Hanson, James R.,Uyanik, Cavit
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p. 1101 - 1114
(2007/10/03)
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- CIRCULAR DICHROISM OF CYCLIC AMINO SUBSTITUTED Δ4-3-KETOSTEROIDS
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The circular dichroism (CD) of various steroidal α,β-unsaturated ketones having cyclic amino substituents near the enone system has been studied and the spectra provide significant information regarding the position and configuration of the substituents.Keywords- steroid; amino-steroid; CD; n-Π* Cotton effect; Π-Π* Cotton effect; steroidal enone; α,β-unsaturated ketone
- Nogami, Yasuyoshi,Koga, Toshitaka
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p. 2274 - 2277
(2007/10/02)
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- FREE-RADICAL OXIDATIVE TRANSFORMATIONS OF ANDROST-4-ENE-3β,9α,17β-TRIOL 3,17-DIACETATE
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The oxidation of androst-4-ene-3β,9α,17β-triol 3,17-diacetate (2) with lead tetraacetate resulted mainly in β-fragmentation of the C(9)-C(10) bond to give a mixture of 10α- and 10β-acetoxy-Δ4-unsaturated 9,10-seco-steroidal ketones (3a and 3b) as the minor components (in ca.7percent yield) and the rearranged 4β-acetoxy-Δ5(10)-unsaturated 9,10-seco-9-ketone (4) as the major product (in 61percent yield).Unexpestedly, when the same substrate (2) was subjected to the mercuric oxide - iodine oxidation, it underwent predominantly α-epoxidation of the olefinic double bond to produce the 4α,5α-epoxy derivative (5) (in 58percent yield).
- Mihailovic, Mihailo LJ.,Lorenc, Ljubinka,Dabovic, Milan,Bjelakovic, Mira
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p. 6201 - 6206
(2007/10/02)
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- Use of aromatase-inhibitors for prophylaxis and/or treatment of benign prostatic hyperplasia
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Aromatase-inhibitors are used in a method of prophylaxis and/or treatment by therapy of prostatic hyperplasia. Pharmaceutical preparations suitable for such a use comprise an aromatase-inhibitor. A particularly preferred aromatase-inhibitor is, for example, testolactone.
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- Reconstruction of Ring A of 3,4-Dinor-2,5-seco Steroids
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Methods for the reconversion of 3,4-dinor-2,5-seco steroids into the parent 4-en-3-one systems are discussed.In an efficient route, reaction of 17β-acetoxy-5,5-ethylenedioxy-3,4-dinor-2,5-secoandrostan-2-al with ethoxyvinyl-lithium led to the corresponding 2ξ-hydroxy-3-one.Acetylation followed by treatment with zinc dust in acetic acid then gave testosterone acetate.A similar series of reactions was performed in the progesterone series.
- Boar, Robin B.,Patel, Arvind C.
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p. 1201 - 1204
(2007/10/02)
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- A Mild and Efficient Degradation of Ring A of Steroids
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17-β-acetoxy-4,5-secoandrost-3-yn-5-one and 4,5-secopregn-3-yne-5,20-dione, readily available by Eschenmoser-Tanabe fragmentaton, have been rearranged to corresponding 2-ynes, which were cleaved to afford 2,5-seco-3,4-dinor-derivatives in excellent overall yield.The release of toluene-p-sulphinic acid during the fragmentation step can lead to the acetylation sulphinylation of an extraneous hydroxy-group.The active sulphinylating species is evidently p-tolyl toluene-p-sulphinyl sulphone.
- Boar, Robin B.,Jones, Susan L.,Patel, Arvind C.
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p. 513 - 516
(2007/10/02)
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