- Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A "visible Light" Approach
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In our continued effort to address the challenges of selective sp3 C-H fluorination on complex molecules, we report a sensitized aliphatic fluorination directed by terpenoidal enones using catalytic benzil and visible light (white LEDs). This sensitized approach is mild, simple to set up, and an economical alternative to our previous protocol based on direct excitation using UV light in a specialized apparatus. Additionally, the amenability of this protocol to photochemical flow conditions and preliminary evidence for electron-transfer processes are highlighted.
- Bume, Desta Doro,Harry, Stefan Andrew,Pitts, Cody Ross,Lectka, Thomas
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p. 1565 - 1575
(2018/02/09)
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- Multiple Enone-Directed Reactivity Modes Lead to the Selective Photochemical Fluorination of Polycyclic Terpenoid Derivatives
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In the realm of aliphatic fluorination, the problem of reactivity has been very successfully addressed in recent years. In contrast, the associated problem of selectivity, that is, directing fluorination to specific sites in complex molecules, remains a great, fundamental challenge. In this report, we show that the enone functional group, upon photoexcitation, provides a solution. Based solely on orientation of the oxygen atom, site-selective photochemical fluorination is achieved on steroids and bioactive polycycles with up to 65 different sp3 C-H bonds. We have also found that γ-, β-, homoallylic, and allylic fluorination are all possible and predictable through the theoretical modes reported herein. Lastly, we present a preliminary mechanistic hypothesis characterized by intramolecular hydrogen atom transfer, radical fluorination, and ultimate restoration of the enone. In all, these results provide a leap forward in the design of selective fluorination of complex substrates that should be relevant to drug discovery, where fluorine plays a prominent role.
- Pitts, Cody Ross,Bume, Desta Doro,Harry, Stefan Andrew,Siegler, Maxime A.,Lectka, Thomas
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supporting information
p. 2208 - 2211
(2017/02/23)
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- 5 α-chloro-androl -6β, 19-epoxy -3,17-dione method for the preparation of
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The invention provides a method for preparing 5 alpha-chlorine-androstane-6 beta, 19-epoxy-3,17-diketone. The method comprises the following steps: taking 4-AD as a raw material, carrying out 3-position enol esterification, reduction, 3,17-position double esterification, 5,6-position addition, 6,19-cyclization and 3,17-position double oxidation, and finally obtaining 5 alpha-chlorine-androstane-6 beta, 19-epoxy-3,17-diketone. The method has the advantages of being rich in raw material sources, environmentally-friendly, low in cost and high in yield of synthetic process, and the obtained 5 alpha-chlorine-androstane-6 beta, 19-epoxy-3,17-diketone can be applied to producing series of family planning drugs.
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Paragraph 0015; 0059-0060
(2018/01/19)
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- Synthesis and antiproliferative activity of some androstene oximes and their O-Alkylated derivatives
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In order to study the structure-activity relationship with respect to the cytotoxicity of steroidal oximes, several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. The oxime ethers were solidified and purified by preparing their corresponding oxalate salts. The new derivatives as well as some previously synthesized ones were evaluated for in vitro antineoplastic activity against a panel of 60 cancer cell lines at 10 μM. The oximes and oxime ethers were found to have moderate to good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines. Several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. Their structure-activity relationship with respect to the cytotoxicity of steroidal oximes was studied. The oximes and oxime ethers were found to have moderate-to-good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines.
- Acharya, Pratap Chandra,Bansal, Ranju
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p. 193 - 199
(2014/03/21)
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- NOVEL SERIES OF IMIDAZOLYL SUBSTITUTED STEROIDAL AND INDAN-1-ONE DERIVATIVES
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The present invention provides a novel series of imidazolyl substituted steroidal and indan-1-one derivatives and salts thereof having the following general structural formulae (A and B)
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Page/Page column 17
(2012/12/13)
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- Synthesis and antineoplastic activity of O-alkylated derivatives of 7-hydroximinoandrost-5-ene steroids
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Varied positioning of the hydroximino group on the parental steroid skeleton results in remarkable changes in the antineoplastic activity profile of the compounds. Here, the compound 7-oximino-5-androstene and its O-alkylated derivatives have been prepared and screened for cytotoxic and aromatase inhibitory activity. The steroidal 7-oximino ether derivatives exhibited insignificant cytotoxic effects when screened against three cancer cell lines, MCF-7 (breast), NCl-H460 (lung), and SF-268 (CNS) at 100 μM. However, the imidazolyl-substituted steroidal oxime ethers displayed moderate inhibition of cytochrome P450 aromatase.
- Bansal, Ranju,Guleria, Sheetal,Ries, Christina,Hartmann, Rolf W.
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scheme or table
p. 377 - 383
(2011/08/03)
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- NOVEL SERIES OF IMIDAZOLYL SUBSTITUTED STEROIDAL AND INDAN-1-ONE DERIVATIVES
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The present invention provides a novel series of imidazolyl substituted steroidal and indan-1-one derivatives and salts thereof having the following general structural formulae (A and B)
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Page/Page column 9-10
(2009/06/27)
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- Zinc(II) iodide-triethylsilane: A novel mild reduction system for direct deoxygenation of aryl aldehydes, ketones, and α,β-unsaturated enones
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ZnI2-TESH has been found to be a novel mild and efficient reduction system. This reagent, in contrast to the traditional ionic deoxygenation systems (TFA-R3SiH, BF3·OEt 2-R3SiH, etc.), could directly deoxygenate different kinds of carbonyl compounds such as aryl aldehydes, ketones, and αβ- unsaturated enones to the corresponding hydrocarbons in moderate to excellent yields. Georg Thieme Verlag Stuttgart.
- Li, Zheng,Deng, Gang,Li, Yuan-Chao
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experimental part
p. 3053 - 3057
(2009/07/03)
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- Mild and selective deprotection method of acetylated steroids and diterpenes by dibutyltin oxide
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Dibutyltin oxide (DBTO) was first utilized for the deacetylation of steroid and diterpene esters. The results showed the deprotection of acetylated steroids and diterpenes separately with moderate catalysis dibutyltin oxide in methanol selectively removed part acetyl groups of these substrates, whereas several functional groups of the steroids and diterpenes were retained and neither isomerization nor degradation of these substrates was observed. It seems that the acetyl groups with lower steric hindrance or near carbonyl, alkoxy, or hydroxyl groups can be cleaved by the reaction, whereas the acetyl groups with higher steric hindrance or without carbonyl, alkoxy, or hydroxyl groups neighboring were retained under the same conditions. One of the interesting results obtained was the selective hydrolysis of the 3β-O-acetyl group in the presence of the 6β group in 3β,6β-Di-O-acetyl-5α-hydroxypregn-16-en-20-one. This allows for subsequent introduction of one unit at C-3 and the other unit at C-6. This procedure is useful for the synthesis of a series of closely related isomers of 3β,5α,6β-trihydroxypregn-16-en-20-one and other widespread polyhydroxysteroids in marine organisms and some terrestrial species.
- Wang, Shao-Min,Zhang, Yan-Bing,Liu, Hong-Min,Yu, Guo-Bin,Wang, Ke-Rang
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- ESTROGEN RECEPTOR MODULATORS
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The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget’s disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.
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Page/Page column 28
(2008/06/13)
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- ESTROGEN RECEPTOR MODULATORS
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The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget’s disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease and cancer, in particular of the breast, uterus and prostate.
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Page/Page column 25
(2008/06/13)
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- Structure-activity relationship study of androstene steroids with respect to local anti-inflammatory activity
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A sex hormone, 37β-acetoxy-17β-hydroxy-androst-5-ene (1) (CAS 1639-43-6), was isolated from aerial parts of Acacia nilotica. This compound is reported to have anti-inflammatory activity. In view of this, considering this molecule as a lead molecule different androstene compounds were synthesized to study their potency and structure-activity relationship with respect to local anti-inflammatory activity. The experiments indicated that 17 ketonic compounds were more active towards inflammation than their oxime analogues. Similarly, for the compounds containing an acetyl group fixed at C-3 position a decreasing trend of activity was observed in the order of ketonic, hydroxyl, oxime and acetyl group, respectively, when these groups are at C-17 position. ECV · Editio Cantor Verlag, Aulendorf.
- Chaubal, Rohini,Mujumdar, Arvind M.,Misar, Ashwini,Deshpande, Vishnu H.,Deshpande, Nirmala R.
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p. 394 - 398
(2007/10/03)
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- ESTROGEN RECEPTOR MODULATORS
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The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget’s disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.
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Page/Page column 26
(2008/06/13)
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- ESTROGEN RECEPTOR MODULATORS
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The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget’s disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.
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Page/Page column 25
(2010/02/11)
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- ESTROGEN RECEPTOR MODULATORS
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The present invention relates to compounds and derivatives thereof, their synthesis, and their use as estrogen receptor modulators. The compounds of the instant invention are ligands for estrogen receptors and as such may be useful for treatment or prevention of a variety of conditions related to estrogen functioning including: bone loss, bone fractures, osteoporosis, metastatic bone disease, Paget's disease, periodontal disease, cartilage degeneration, endometriosis, uterine fibroid disease, hot flashes, increased levels of LDL cholesterol, cardiovascular disease, impairment of cognitive functioning, cerebral degenerative disorders, restenosis, gynecomastia, vascular smooth muscle cell proliferation, obesity, incontinence, inflammation, inflammatory bowel disease, sexual dysfunction, hypertension, retinal degeneration and cancer, in particular of the breast, uterus and prostate.
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Page/Page column 27
(2010/02/14)
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- Radical deoxygenation of hydroxyl groups via phosphites
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A highly efficient, two-step sequence method for the deoxygenation of hydroxyl groups has been developed. The method involves the preparation of the 2-(2-iodophenyl)ethyl methyl phosphite derivative of an alcohol using methyl dichlorophosphite and 2-(2-iodophenyl)ethanol. Treatment of the phosphite intermediate with (n-Bu)3SnH/AIBN in refluxing benzene cleanly produces the deoxygenation product of the original alcohol. Copyright
- Zhang, Liming,Koreeda, Masato
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p. 13190 - 13191
(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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- Novel stereoselective synthesis of 7β-methyl-substituted 5-androstene derivatives
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The 7β-methyl-5-androstene derivatives 11a-c were prepared in good yield with high stereoselectivities starting from 3β-acetoxyandrost-5-en-17-one 4. The addition of methylmagnesium iodide to the 7-carbonyl group of 7a-c gave, after hydrolysis, two isomers 9a-c and 10a-c, which were stereoselectively deoxygenated by means of an ionic hydrogenation to afford the compounds 11a-c.
- Zheng, Yunhong,Li, Yuanchao
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p. 1603 - 1606
(2007/10/03)
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- Chloro- or bromo-trimethylsilane induced rapid and quantitative acid-ester conversion for steroid based alcohols with various carboxylic acids under solvent free conditions
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Steroid based higher alcohols are rapidly esterified in quantitative yield with a number of carboxylic acids in the presence of TMSCl or TMSBr generally under solvent free conditions.
- Goswami, Papori,Hazarika, Saroj,Borah, Parinita,Chowdhury, Pritish
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p. 678 - 682
(2007/10/03)
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- SYNTHESIS OF 19-HYDROXYSTEROIDS I. NEW SYNTHESIS OF 19-HYDROXYTESTOSTERONE
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For obtaining 19-hydroxytestosterone from dehydroepiandrosterone a new scheme of synthesis has been developed the key stages of which are the reduction of the 17-keto group to a 17-alcohol, the functionalization of the 19-methyl group via the bromohydrin with the formation of a 6β,19-epoxide, the selective hydrolysis of the free β-acetoxy group, the conversion of the 3β-hydroxy-5α-bromo derivative into the Δ4-3-ketone, and the reductive cleavage of the 6β,19-epoxide ring.
- Kovganko, N. V.,Kashkan, Zh. N.,Chernov, Yu. G.
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p. 584 - 588
(2007/10/02)
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- A New Method for the Oxidation of Alkenes to Enones. An Efficient Synthesis of Δ5-7-Oxo-Steroids
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A variety of cycloalkenes were converted into α,β-unsaturated ketones using t-butyl hydroperoxide in the presence of chromium hexacarbonyl catalyst.The scope of the reaction has been partly invstigated, and it was found that the allylic oxidation proceeds selectively in the presence of some secondary alcohols.High-yield conversions of steroidal 5,6-enes into the corresponding 5,6-en-7-ones are reported.
- Pearson, Anthony J.,Chen, Yong-Shing,Han, Gi Rin,Hsu, Shih-Ying,Ray, Tapan
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p. 267 - 274
(2007/10/02)
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