- A Mild Method for the Preparation of Unsaturated Alcohols from 1,3-Glycols via Dimethylformamide Acetals
-
Provided it possesses a hydrogen atom suitably placed for elimination, a 1,3-glycol may be converted into an unsaturated alcohol via quaternization of its dimethylformamide acetal.
- Ackland, Mark J.,Gordon, John F.,Hanson, James R.,Yeoh, Boon Leng,Ratcliffe, Arnold H.
-
-
Read Online
- Positive Modulators of the N-Methyl- d -aspartate Receptor: Structure-Activity Relationship Study of Steroidal 3-Hemiesters
-
Here, we report the synthesis of pregn-5-ene and androst-5-ene dicarboxylic acid esters and explore the structure-activity relationship (SAR) for their modulation of N-methyl-d-aspartate receptors (NMDARs). All compounds were positive modulators of recombinant GluN1/GluN2B receptors (EC50 varying from 1.8 to 151.4 μM and Emax varying from 48% to 452%). Moreover, 10 compounds were found to be more potent GluN1/GluN2B receptor modulators than endogenous pregnenolone sulfate (EC50 = 21.7 μM). The SAR study revealed a relationship between the length of the residues at carbon C-3 of the steroid molecule and the positive modulatory effect at GluN1/GluN2B receptors for various D-ring modifications. A selected compound, 20-oxo-pregnenolone hemiadipate, potentiated native NMDARs to a similar extent as GluN1/GluN2A-D receptors and inhibited AMPARs and GABAAR responses. These results provide a unique opportunity for the development of new steroid based drugs with potential use in the treatment of neuropsychiatric disorders involving hypofunction of NMDARs.
- Krausova, Barbora,Slavikova, Barbora,Nekardova, Michaela,Hubalkova, Pavla,Vyklicky, Vojtech,Chodounska, Hana,Vyklicky, Ladislav,Kudova, Eva
-
p. 4505 - 4516
(2018/05/15)
-
- Androl -3β, 5 α, 6β, 19-tetrol and its preparation method and application
-
The invention provides a polyhydroxy sterol compound androstane-3beta, 5alpha, 6beta,19-tetraol, and a preparation method and an application thereof. The compound has significant inhibitory activity on aldo-keto reductase AKR1B10 and shows good selectivity, can be used as a selective inhibitor of the aldo-keto reductase AKR1B10. The compound disclosed by the invention is cheap and available in synthesis material, scientific and reasonable in synthesis route, high in synthesis yield of each step, and simple and convenient to operate.
- -
-
Paragraph 0019; 0049-0050
(2017/03/14)
-
- Catalytic Ring-Opening of Cyclic Alcohols Enabled by PCET Activation of Strong O-H Bonds
-
We report a new photocatalytic protocol for the redox-neutral isomerization of cyclic alcohols to linear ketones via C-C bond scission. Mechanistic studies demonstrate that key alkoxy radical intermediates in this reaction are generated via the direct homolytic activation of alcohol O-H bonds in an unusual intramolecular PCET process, wherein the electron travels to a proximal radical cation in concert with proton transfer to a weak Br?nsted base. Effective bond strength considerations are shown to accurately forecast the feasibility of alkoxy radical generation with a given oxidant/base pair.
- Yayla, Hatice G.,Wang, Huaiju,Tarantino, Kyle T.,Orbe, Hudson S.,Knowles, Robert R.
-
p. 10794 - 10797
(2016/09/09)
-
- Synthesis and cytotoxicity of (3β)-3-acetyloxy-5(6)-androsten-7-one oxime and 3,5(6)-androstadien-7-one oxime
-
(3β)-3-Acetyloxy-5(6)-androsten-7-one oxime and 3,5(6)-androstadien-7- one oxime were synthesized and their in vitro cytotoxic activities against human epidermoid carcinoma cell line KB, human cervical carcinoma cell line HeLa, human gastric carcinoma cell line MKN-28, and human breast carcinoma cell line MCF-7 were evaluated. The compound (3b)-3-acetyloxy-5(6)-androsten-7-one oxime exhibited significant growth inhibitory properties against cell lines tested and afforded IC 50 value 26.0 ± 1.6, 12.8 ± 1.0, 18.1 ± 0.2, 10.2 ± 1.2 lM for KB, HeLa, MKN-28, and MCF-7, respectively. Springer Science+Business Media 2013.
- Yao, Juan,Ye, Weijian,Liu, Jinliang,Liu, Juanjuan,Wang, Cunde
-
p. 1839 - 1843
(2014/05/06)
-
- A synthetic steroid 5α-Androst-3β,5,6-Triol blocks hypoxia/reoxygenation - Induced neuronal injuries via protection of mitochondrial function
-
Ischemic stroke is a leading cause of death worldwide, yet therapies are limited. During periods of ischemia following reperfusion in ischemic stroke, not only loss of energy supply, but a few other factors including mitochondrial dysfunction and oxidative stress also make vital contribution to neuronal injury. Here we synthesized a steroid compound 5α-androst-3β,5, 6β-triol by 3 steps starting from dehydroepiandrosterone and examined its effect on mitochondrial function and oxidative stress in primary cultured cortical neurons exposed to hypoxia followed by reoxygenation. 5α-Androst-3β,5,6β-triol dose-dependently protected cortical neurons from hypoxia/reoxygenation exposure. Rates of reduction in neuronal viability, loss of mitochondrial membrane potential, disruption of ATP production and oxidative stress were ameliorated in 5α-androst-3β,5, 6β-triol pretreated cultures. In summary, these results suggest that 5α-androst-3β,5,6β-triol is neuroprotective against hypoxia/reoxygenation induced neuronal injuries through mediation of mitochondrial function and oxidative stress.
- Chen, Jiesi,Leng, Tiandong,Chen, Wenli,Yan, Min,Yin, Wei,Huang, Yijun,Lin, Suizhen,Duan, Dayue,Lin, Jun,Wu, Gongxiong,Zhang, Jingxia,Yan, Guangmei
-
p. 996 - 1002
(2013/10/21)
-
- Novel and efficient synthesis and antifungal evaluation of 2,3-functionalized cholestane and androstane derivatives
-
Synthetic modifications of cholesterol and other traditional steroid molecules have become a promising area for the exploration and development of novel antifungal agents, especially with respect to the development of fatty-acid esters of steroids. In addition, 2,3-functionalized steroids are also compounds with potentially interesting biological properties and proper functionalization of 2,3-steroids can lead to the development of efficient syntheses of building blocks for novel fatty-acid esters of steroids. In this Letter, we outline a novel and efficient approach to the synthesis of 2,3-functionalized cholestane and androstane derivatives and present their promising preliminary antifungal activities against a number of fungal species.
- Jursic, Branko S.,Upadhyay, Sunil Kumar,Creech, Clinton C.,Neumann, Donna M.
-
supporting information; experimental part
p. 7372 - 7375
(2011/02/23)
-
- First synthesis of 7α- and 7β-amino-DHEA, dehydroepiandrosterone (DHEA) analogues and preliminary evaluation of their cytotoxicity on Leydig cells and TM4 Sertoli cells
-
Efficient syntheses of new DHEA analogues, and their apoptotic and necrotic effects on Leydig cells and TM4 Sertoli cells are described. The key step in the synthetic strategy of 7-amino-DHEA derivatives involves a bromination on C-7 position to give an epimeric mixture of bromides which were substituted by azides and reduced to give 7α- and 7β-amino-3β-hydroxyandrost-5-en-17-ones. No cytotoxic effect induced by apoptosis mechanism was observed on Leydig and TM4 Sertoli cells by treatment with these amino-DHEA analogues. A necrotic effect was induced only in TM4 Sertoli cells. The best activity was obtained with 7α,β-amino-androst-5-en-3β-ol and 7β-amino-3β-hydroxy-androst-5-en-17-one.
- Bazin, Marc-Antoine,Travert, Carine,Carreau, Serge,Rault, Sylvain,Kihel, La?la El
-
p. 3152 - 3160
(2008/02/07)
-
- A selective Cu(II)/Fe(III)-mediated hydrogenation of steroidal haloalkenes in the presence of hydrazine
-
A new system for hydrogenation of haloalkenes is reported. Cu(II)/Fe(III)-mediated selective hydrogenation of steroidal haloalkenes in the presence of hydrazine proves to be a very efficient method for the synthesis of 17β-halosteroids, potential candidates as antiestrogens or androgen receptor-mediated imaging agents. The reaction stereospecifically affords β-haloalkanes without any concomitant formation of dehalogenation products.
- Chang, Kai-Hsuan,Jenkins, Malikah N.,Wu, Hsin-Ru,Li, Wen-Shan
-
p. 1351 - 1354
(2007/10/03)
-
- Synthesis of cytotoxic 6E-hydroximino-4-ene steroids: Structure/activity studies
-
In an effort to determine the pharmaceutical utility and the structural requirements for activity against various tumor cell lines, several 6E-hydroximino-4-ene steroids with different side chains and degrees of unsaturation on ring A were synthesized in our laboratory. Evaluation of the synthesized compounds for cytotoxicity against P-388, A-549, HT-29, and MEL-28 tumor cells revealed that some important structural features are required for activity. The presence of a cholesterol-type side chain, which appears to play a major role in determining the biological activity, the existence of a ketone functionality at C-3, and an elevated degree of oxidation on ring A all result in higher bioctivity than other structural motifs.
- Deive,Rodríguez,Jiménez
-
p. 2612 - 2618
(2007/10/03)
-
- Methods and compositions for attracting and controlling termites
-
The present invention provides a composition for attracting termites containing a steroid derivative of formula I The present invention also provides a method for attracting or controlling termites with the composition.
- -
-
-
- Imprinted polymers as protecting groups for regioselective modification of polyfunctional substrates
-
Imprinted polymers were prepared using a functional monomer derived from boronophthalide and a number of steroid templates bearing spatially separated hydroxyl groups. The cooperative nature of the binding interaction was demonstrated in polymers imprinted with androst-5-ene-3β,17β-diol and its structural analogues. The stoichiometry and kinetics of binding were probed using IR spectroscopy, selective solvent extractions, and chemical modification experiments. The feasibility of using imprinted polymers as reusable protecting groups was established by the regioselective acylation of trihydroxysteroids bound to polymers imprinted with structurally related diols. In polymers prepared with tert-butyl ester templates "matched" to the substrate, regioselectivities as high as 23.1:1 (24-acetate:3-acetate) in the monoester products (65% of recovered material) were seen. In the "unmatched" case, the ratio fell to 5.4:1; however, in functionally identical control polymers, imprinted with ethylene glycol, the regioselectivity was completely reversed (1:100), and only poor yields of monoesters (13%) were obtained.
- Alexander, Cameron,Smith, Craig R.,Whitcombe, Michael J.,Vulfson, Evgeny N.
-
p. 6640 - 6651
(2007/10/03)
-
- Methods and compositions for attracting and controlling termites
-
The present invention provides a composition for attracting termites containing a steroid derivative of formula I The present invention also provides a method for attracting or controlling termites with the composition.
- -
-
-
- Synthesis of some analogues of blattellastanoside A, the steroidal aggregation pheromone of the German cockroach
-
Blattellastanoside A, the aggregation pheromone of the German cockroach, is a chlorinated steroid glucoside with the 5β-stigmastane skeleton. Its analogues were synthesized in order to clarify the structure-activity relationship. They are 1a with the 5β-cholestane skeleton, 1b with the 5β-androstane skeleton, 1c with a fluorine substituent instead of the chlorine and 1d with a β-D-galactopyranose instead of the β-D-glucopyranose of the original pheromone. Their bioassay shows that 1a and 1c are active, while 1b and 1d are totally devoid of pheromone activity. The aglycone of blattellastanosides A and B were active.
- Mori, Kenji,Nakayama, Toru,Sakuma, Masayuki
-
p. 401 - 408
(2007/10/03)
-
- Antenna-initiated photochemistry in polyfunctional steroids. Intramolecular singlet and triplet energy transfer between aryl, ketone, and alkene groups in 6β-(Dimethylphenylsiloxy)-5β-androstanes 1
-
Steroids have been prepared that bear a dimethylphenylsiloxy (DPSO) group and additional C3 and/or C17 ketone functionalities. The DPSO group has been used to harvest 266 nm photons and then activate the ketone functionalities through intramolecular singlet-singlet energy transfer (intra-SSET). Thus, the monoketones 3,3-(ethylenedioxy)-6β-(DPSO)-5β-androstan-17-one (6) and 6β-(DPSO)-5β-androstan-3-one (8) both exhibit DPSO-initiated photochemistry at the carbonyl groups. Irradiation of the diketone, 6β-(DPSO)-5β-androstane-3,17-dione (5), gives two ring D-derived photoproducta, an epimer (19) and an enal (18), both coming from the C17 ketone excited singlet state. Here Φintra-SSET from the aryl antenna to the carbonyl groups is ca. 88% efficients and occurs with a rate of ca. 6.5 × 109 s-1, with the chemistry indicative of facile intra-SSET between the C3 and C17 ketones. The alkylidene group at C3 (i.e., as in 6β-(DPSO)-3(E)-ethylidene-5β-androstan-17-one (33) and its Z isomer (34)) has no effect on the rate or efficiency of aryl activation of the C17 ketone.
- Jiang, S. Anna,Xiao, Changhe,Morrison, Harry
-
p. 7045 - 7055
(2007/10/03)
-
- A Mild Method for the Conversion of 1,3-Glycols into Unsaturated Alcohols
-
Some transformations of 1,3-glycols utilizing dimethylformamide dimethyl acetal have been examined with the diterpenoids aphidicolin and foliol and some steroids as substrates.Axial alcohols with a suitably disposed trans hydrogen atom undergo an elimination reaction to give the formate of an unsaturated alcohol via the quaternary salt of the cyclic formamido acetal.
- Ackland, Mark J.,Gordon, John F.,Hanson, James R.,Yeoh, Boon Leng,Ratcliffe, Arnold H.
-
p. 2013 - 2018
(2007/10/02)
-
- Identification by gas chromatography mass spectrometry of intermediates in the aromatization of modified C19 steroids by human placental microsomes
-
Analogs of 4 androstene 3,17 dione and testosterone were tested as substrates for the aromatizing enzyme complex of human placenta. Compounds modified in rings B, C, and D were found to be aromatized via a pathway similar to that postulated for 4 androstene 3,17 dione and testosterone, in which oxidation to the 19 hydroxy and 19 oxo (or corresponding gem diol) intermediates occurs. No evidence of additional intermediates was obtained.
- Braselton Jr,Orr,Engel
-
p. 411 - 433
(2007/10/13)
-