- Ring-closing metathesis approaches towards the total synthesis of rhizoxins
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Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ringclosure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) E double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.
- Altmann, Karl-Heinz,Liniger, Marc,Neuhaus, Christian M.
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supporting information
(2020/10/18)
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- Preparation method of 3-methyl-3-penten-2-one
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The invention discloses a preparation method of 3-methyl-3-penten-2-one. The preparation method comprises the following steps: with butanone as a raw material, performing 3-position halogenation to obtain 3-halobutanone (1), then performing a ketalation reaction to obtain 3-halobutanonediol (2), then performing a Grignard reaction to obtain a Grignard reagent, performing nucleophilic addition on the Grignard reagent and acetaldehyde, and performing intramolecular dehydration under the conditions of acid catalysis and heating to obtain a target product, namely the 3-methyl-3-penten-2-one (3). The preparation method has the advantages of easy obtainment of the raw material, a wide raw material source, simpleness, low preparation cost and suitability for industrial production; by the preparation method, the problems of high preparation cost and difficult industrial production in the prior art are solved.
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Paragraph 0012-0016
(2019/01/08)
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- METALLOENZYME INHIBITOR COMPOUNDS
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The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
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Page/Page column 265; 266
(2017/07/31)
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- Design, synthesis and antifungal activity of novel furancarboxamide derivatives
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Twenty-seven novel furancarboxamide derivatives with a diphenyl ether moiety were synthesized and evaluated for their antifungal activity against Rhizoctonia solani, Botrytis cirerea, Valsa Mali and Sphaceloma ampelimum. Antifungal bioassay results indicated that most compounds had good or excellent fungicidal activities for R. solani and S. ampelimum at 20 mg L-1. Among synthesized compounds, compound 18e showed a greater inhibitory effect against S. ampelimum, with half maximal effective concentration (EC50) values of 0.020 mg L-1. This strong activity rivals currently used commercial fungicides, such as Boscalid and Carbendazim, and has great potential as a lead compound for future development of novel fungicides.
- Wen, Fang,Jin, Hong,Tao, Ke,Hou, Taiping
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p. 244 - 251
(2016/05/24)
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- Stereodivergent Synthesis of Chromanones and Flavanones via Intramolecular Benzoin Reaction
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The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.
- Wen, Genfa,Su, Yingpeng,Zhang, Guoxiang,Lin, Qiqiao,Zhu, Yujin,Zhang, Qianqian,Fang, Xinqiang
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supporting information
p. 3980 - 3983
(2016/09/09)
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- Aminoazabenzimidazoles, a Novel Class of Orally Active Antimalarial Agents
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Whole-cell high-throughput screening of the AstraZeneca compound library against the asexual blood stage of Plasmodium falciparum (Pf) led to the identification of amino imidazoles, a robust starting point for initiating a hit-to-lead medicinal chemistry effort. Structure-activity relationship studies followed by pharmacokinetics optimization resulted in the identification of 23 as an attractive lead with good oral bioavailability. Compound 23 was found to be efficacious (ED90 of 28.6 mg·kg-1) in the humanized P. falciparum mouse model of malaria (Pf/SCID model). Representative compounds displayed a moderate to fast killing profile that is comparable to that of chloroquine. This series demonstrates no cross-resistance against a panel of Pf strains with mutations to known antimalarial drugs, thereby suggesting a novel mechanism of action for this chemical class.
- Hameed P, Shahul,Chinnapattu, Murugan,Shanbag, Gajanan,Manjrekar, Praveena,Koushik, Krishna,Raichurkar, Anandkumar,Patil, Vikas,Jatheendranath, Sandesh,Rudrapatna, Suresh S.,Barde, Shubhada P.,Rautela, Nikhil,Awasthy, Disha,Morayya, Sapna,Narayan, Chandan,Kavanagh, Stefan,Saralaya, Ramanatha,Bharath, Sowmya,Viswanath, Pavithra,Mukherjee, Kakoli,Bandodkar, Balachandra,Srivastava, Abhishek,Panduga, Vijender,Reddy, Jitender,Prabhakar,Sinha, Achyut,Jiménez-Díaz, María Belén,Martínez, María Santos,Angulo-Barturen, I?igo,Ferrer, Santiago,Sanz, Laura María,Gamo, Francisco Javier,Duffy, Sandra,Avery, Vicky M.,Magistrado, Pamela A.,Lukens, Amanda K.,Wirth, Dyann F.,Waterson, David,Balasubramanian,Iyer, Pravin S.,Narayanan, Shridhar,Hosagrahara, Vinayak,Sambandamurthy, Vasan K.,Ramachandran, Sreekanth
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supporting information
p. 5702 - 5713
(2014/08/05)
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- Silica gel catalyzed α-bromination of ketones using N-bromosuccinimide: An easy and rapid method
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An easy and rapid method for the α-bromination of ketones using N-bromosuccinimide (NBS) catalyzed by silica gel in methanol under reflux conditions was developed. The expected products were formed in excellent isolated yields within a short period of time (5-20 min). Major advantages of the present procedure include use of inexpensive and readily available catalyst, exclusion of pre- and post-chemical treatment of catalyst and use of methanol as solvent instead of ethers and chlorinated solvents.
- Mohan Reddy, Bodireddy,Venkata Ramana Kumar, Velpula,Chinna Gangi Reddy, Nallagondu,Mahender Rao, Siripragada
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p. 179 - 182
(2014/02/14)
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- CXCR4 Receptor Antagonists
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Disclosed are compounds that are antagonists of the CXCR4 receptor.
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Paragraph 0126; 0127
(2013/11/06)
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- CXCR4 RECEPTOR ANTAGONISTS
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The compounds of formula (I) are antagonists of the CXCR4 receptor Wherein R1, X, Y and R2 are as defined in the claims.
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Page/Page column 35
(2012/05/04)
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- Oxidative bromination of ketones using ammonium bromide and oxone
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A highly efficient, environmentally safe and economic method for selective α-monobromination of aralkyl, cyclic, acyclic, 1,3-diketones and β-keto esters and α,α-dibromination of 1,3-diketones and β-keto esters without catalyst is reported using ammonium bromide as a bromine source and oxone as an oxidant. The reaction proceeds at ambient temperature and yields range from moderate to excellent. Bromination of unsymmetrical ketones takes place at the less substituted α-position predominantly. Aromatisation of tetralones is also carried out with this reagent system.
- MacHarla, Arun Kumar,Chozhiyath Nappunni, Rohitha,Marri, Mahender Reddy,Peraka, Swamy,Nama, Narender
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supporting information; experimental part
p. 191 - 195
(2012/01/17)
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- Substituted 2-aminothiazoles are exceptional inhibitors of neuronal degeneration in tau-driven models of Alzheimer's disease
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A novel series of 2-aminothiazoles with strong protection in an Alzheimer's disease (AD) model comprising tau-induced neuronal toxicity is disclosed. These derivatives can be synthesized in one-pot and a small SAR of the substitution within these series afforded several compounds that counteracted tau-induced cell toxicity at nanomolar concentrations. These congeners therefore have strong potential as possible treatment for Alzheimer's disease and other related tauopathies.
- Lagoja, Irene,Pannecouque, Christophe,Griffioen, Gerard,Wera, Stefaan,Rojasdelaparra, Veronica Maria,Van Aerschot, Arthur
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experimental part
p. 386 - 392
(2012/05/31)
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- Fast oxidation of secondary alcohols by the bromate-bromide system using cyclic microwave heating in acidic water
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We report an improved, gentle, cyclic microwave activation technique for the oxidation of secondary alcohols using nonhazardous hypobromous acid (BrOH) as the reagent in acidic water. Several aliphatic and aromatic secondary alcohols were successfully oxidized to the corresponding ketones using this technique in high yields and with only minor amounts of side products.
- P??kk?nen, Sanna,Pursiainen, Jouni,Lajunen, Marja
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scheme or table
p. 6695 - 6699
(2011/02/23)
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- PYRAZOLE COMPOUNDS
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The present invention is directed to compounds of Formula (I) and to pharmaceutically acceptable salts thereof, their synthesis, and their use as Raf inhibitors.
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Page/Page column 77
(2009/03/07)
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- A convenient one-pot synthesis of thiazol-2-imines: application in the construction of pifithrin analogues
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For the first time a reaction intermediate has been isolated giving further insight into the mechanism of thiazol-2-imine formation. The first step of the reaction requires a basic medium, while the second step is an acid mediated E1 elimination reaction. An efficient one-pot synthesis of substituted thiazol-2-imines have been achieved by the condensation of carbonyl compounds with thioureas and 1,3-disubstituted thioureas using 1,1′-(ethane-1,2-diyl)dipyridinium bistribromide (EDPBT). Unsymmetrical 1,3-disubstituted thioureas give regioselective products with symmetrical ketones, which are mainly governed by the pKas of NH protons of thiourea, whereas symmetrical 1,3-disubstituted thioureas give regioselective products with symmetrical carbonyl compounds owing to the regioselective bromination of ketones. The methodology is extended to access novel neurodegenerative drug candidate pifithrin-α analogues in good yields in shorter reaction time. This method is simple, versatile and is applicable for different 1,3-disubstituted thioureas as well as a range of carbonyl compounds.
- Murru, Siva,Singh,Kavala, Veerababurao,Patel, Bhisma K.
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p. 1931 - 1942
(2008/09/17)
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- Tetrameric DABCO-bromine: An efficient and versatile reagent for bromination of various organic compounds
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Tetrameric DABCO-bromine is a powerful brominating agent but shows reasonable selectivity with certain substrates. The selective bromination for activated aromatic compounds and alkenes is reported. Synthesis of α-bromo ketones and nitriles has also been achieved by using this reagent and the results are also reported. All products reported were obtained in good to excellent yields.
- Heravi, Majid M.,Derikvand, Fatemeh,Ghassemzadeh, Mitra
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p. 125 - 128
(2007/10/03)
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- Synthesis of Polysantol and related sandalwood-type odorants using magnesium α-bromoketone enolates
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The syntheses of the commercial sandalwood-type odorant Polysantol and several structurally related compounds are described. The methodology followed is based on a selective and efficient magnesium-mediated aldol reaction of the starting material, α-campholenic aldehyde and different α-bromoketones. Dehydration of the resulting secondary alcohol and reduction of the carbonyl group allowed the completion of the syntheses of the target molecules in 30-56% overall yields.
- Castro, Juan M.,Linares-Palomino, Pablo J.,Salido, Sofía,Altarejos, Joaquín,Nogueras, Manuel,Sánchez, Adolfo
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p. 2619 - 2622
(2007/10/03)
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- A mild, convenient, and inexpensive procedure for conversion of vinyl halides to α-haloketones
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Treatment of a vinyl chloride with commercially available aqueous sodium hypochlorite solution in a 2:5 mixture of acetic acid/acetone at 0 °C for about 1 h cleanly leads to the corresponding α-chloroketone. Similarly, if a vinyl bromide is exposed to sodium hypobromite (freshly prepared from bromine and sodium hydroxide) at 0 °C in 2:5 acetic acid/acetone as solvent, an α-bromoketone is produced. This methodology has been applied to a number of vinyl chlorides and vinyl bromides, and the transformations generally proceed in high yields. The mild reaction conditions are compatible with a variety of functional groups including amides, esters, and imines.
- VanBrunt, Michael P.,Ambenge, Reuben O.,Weinreb, Steven M.
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p. 3323 - 3326
(2007/10/03)
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- Kinetic study of the self-reactions of the BrCH2CH2O2 and BrCH(CH3CH(CH3O2 radicals between 275 and 373 K
-
A conventional flash photolysis technique was used to measure the self-reaction rate constants of the primary BrCH2CH2O2 (2-bromoethylperoxy) and secondary BrCH(CH3)CH(CH3)O2 (2-bromo-l-methylpropylperoxy) β-brominated peroxy radicals, at temperatures in the range of 275-373 K. The absolute UV absorption spectra of BrCH2CH2O2 and BrCH(CH3)CH(CH3)O2 were also measured and compared to those obtained previously for these radicals. The temperature dependence of the self-reaction rate constants provided the following Arrhenius expressions: k(BrCH2CH2O2 + BrCH2CH2O2) = (6.15+5.152.99) × 10-14 exp{(1247 ± 203) K/T} cm3 molecule-1 s-1 and k(BrCH(CH3)CH(CH3)O2 + BrCH(CH3)CH(CH3)O2) = (7.60+22.05-5.65) × 10-15 exp{(1305 ± 428) K/T} cm3 molecule-1 s-1, where the uncertainties represent 95% confidence limits associated with the statistical fitting procedure and include the contribution for the expanded uncertainties in the individual rate constant. These results confirm the enhancement of the peroxy radical self-reaction reactivity upon β-substitution, which is similar for Br, Cl, or OH substituents. Structure-activity relationships are proposed for self-reactions of β-substituted peroxy radicals.
- Villenave, Eric,Moisan, Sandy,Lesclaux, Robert
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p. 2470 - 2477
(2007/10/03)
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- Asymmetric synthesis of α-chiral ketones by the reduction of enones with baker's yeast
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Baker's yeast-mediated asymmetric reduction of α,β-unsaturated ketones (enones) having a pyridyl ring affords the corresponding optically active α-substituted ketones (α-chiral ketones) with excellent stereoselectivity. The position of the heteroatom, as well as the bulk of the α-substituent, plays an important role in governing the stereoselectivity in the reduction of a carbon-carbon double bond.
- Kawai, Yasushi,Hayashi, Motoko,Tokitoh, Norihiro
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p. 3007 - 3013
(2007/10/03)
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- Pyrrole derivatives and medicinal composition
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The invention relates to a pharmaceutical composition comprising a pyrrole derivative of the following formula [1] or a pharmaceutically acceptable salt thereof, or a solvate of either of them, as an active ingredient. STR1 (wherein R1 represents hydrogen or alkoxycar91 bonylamino, R2 represents alkyl, aryl which may be substituted, aromatic heterocyclyl which may be substituted, unsubstituted amino, monoalkylamino, dialkylamino, or cyclic amino which may be substituted; R3 represents cyano or carbamoyl; R4 represents hydrogen or alkyl; E represents alkylene; q is equal to 0 or 1, A represents methyl, aryl which may be substituted, or aromatic heterocyclyl which may be substituted). The pharmaceutical composition of the invention is effective for the treatment of pollakiuria or urinary incontinence.
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-
- SELECTIVE MONOBROMINATION OF KETONES BY BIS(DIMETHYLACETAMIDE)HYDROGEN TRIBROMIDE
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A unified procedure for the α-monobromination of ketones by bis(dimethylacetamide)hydrogen tribromide in methanol is proposed.Methyl aryl ketones with donating and moderately accepting substituents in the ring readily enter into the reaction. 1-Bromo ketones are mostly formed during the bromination of methyl alkyl ketones.
- Rodygin, M. Yu.,Mikhailov, V. A.,Savelova, V. A.
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p. 881 - 887
(2007/10/02)
-
- 2-Bromoethylperoxy and 2-Bromo-1-methylpropylperoxy Radicals: Ultraviolet Absorption Spectra and Self-reaction Rate Constants at 298 K
-
The self-reaction rate constants and UV absorption spectra of two brominated peroxy radicals, BrCH2CH2O2 (2-bromoethylperoxy) and (CH3)BrCHCH(CH3)O2 (2-bromo-1-methylpropylperoxy) have been measured using the molecular modulation technique.Self-reaction rate constants (kobs) of (6.2 +/- 1.2) x 10-12 and (9.6 +/- 1.9) x 10-13 cm3 molecule-1 s-1 were obtained for BrCH2CH2O2 and (CH3)BrCHCH(CH3)O2, respectively.In both cases secondary chemistry is likely to enhance the removal rate of the radicals and the given rate constants are expected to be slightly higher than the true value.The UV spectra of both radicals are broad absorptions with maxima close to 240 nm.Absolute cross-sections at 270 nm were found to be (2.2 +/- 0.4) x 10-18 and (2.8 +/- 0.6) x 10-18 cm2 molecule-1 for BrCH2CH2O2 and (CH3)BrCHCH(CH3)O2, respectively.The measured values of self-reaction rate constants and UV absorption spectra are compared to results for C2H5O2.In addition, a long-lived transient absorption was observed in the BrCH2CH2O2 experiments, and is thought to be due to BrCH2CH2OOBr, a product of an association reaction between Br atoms and BrCH2CH2O2.
- Crowley, John N.,Moortgat, Geert K.
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p. 2437 - 2444
(2007/10/02)
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- Terpenes and Terpene Derivatives, XXIX Synthesis and Olfactive Properties of (-)- and rac-Silphiperfol-5-en-3-ol and of Some Tris-nor Derivatives
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The new sesquiterpene alcohols silphiperfol-5-en-3-ol and the corresponding 7-epi compound (+)-1b, important constituents of the essential oil of Artemisia laciniata have been synthesized in 13 steps by starting from (R)-(+)-pulegone (6) in an overall yield of 8percent.The key reaction is the copper-catalyzed 1,4-Grignard addition of the iodo acetal 34 to the enone (+)-4 in the presence of TMSCl and TMEDA to give the silyl ether 38.Hydrolysis with spontaneous aldol cyclization and dehydration leads to the silphiperfolenones (+)-2a,b which are separable by flash chromatgraphy.The reduction with L-selectrideR gives the alcohols (-)-1a and (+)-1b which are identical in all physical properties with the isolated natural compound.With LiAlH4 the diastereoisomers 42a,b are formed.Olfactive evaluation of the isomers (-)-1a and (+)-1b has shown that the odor of the naturally occuring mixture of 1a,b with the descriptors woody, ambergris, slightly camphoraceous is correctly assigned. (-)-1a represents the more woody and camphoraceous, (+)-1b the more animal facette of ambergris.The odor of rac-1a,b, of the diasteroisomers 42a,b and of the ketones (+)-2a,b is also described as well as that of the tris-nor-silphiperfolene derivatives 29-31. Key Words: Artemisia laciniata / Sesquiterpene alcohols, tricyclic / Structure-odor correlation / (R)-(+)-Pulegone / 1,4-Grignard reaction
- Weyerstahl, Peter,Brendel, Joachim
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p. 669 - 678
(2007/10/02)
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- NOVEL BROMINATION REAGENTS. HEXABROMOCYCLOPENTADIENE: BROMINATION OF ACTIVATED SATURATED SITES
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Hexabromocyclopentadiene (HBC) readily brominates α-keto and benzylic sites, apparently by bromonium ion transfer.
- Magen, Shulamit,Oren, Jakob,Fuchs, Benzion
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p. 3369 - 3372
(2007/10/02)
-
- REACTION OF α-NITRO EPOXIDES WITH HYDROHALIC ACIDS AND THEIR SALTS
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The reaction of α-nitro epoxides of the aliphatic series with hydrohalic acids and their salts leads to the formation of the corresponding α-halogencarbonyl compounds.
- Sokolov, N. A.,Tishchenko, I. G.,Kovganko, N. V.
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p. 248 - 250
(2007/10/02)
-
- Effet d'engrenage. VIII. Extension a des derives fonctionnels de l'alanine
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The gear effect has been discovered and studied for the first time on molecules where the interacting groups were alkyl substituents.In order to be closer to biochemical models, this effect has now been studied where one interacting group is asymmetric and functional.For this purpose eighteen new compounds derived from alanine have been prepared and studied by nmr and dynamic nmr.The gear effect is operating, and it appears to be a suitable means to modulate the interaction of two active functions.
- Blaive, Bruno,Roussel, Christian,Metzger, Jacques,Sandstroem, Jan
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p. 2212 - 2220
(2007/10/02)
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