- Novel photohydration of non-conjugated aryl/olefin bichromophores within cyclodextrin cavities
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Cyclodextrin media are used to achieve photochemical water addition to isolated, acyclic double bonds via intramolecular interaction with excited arenes.
- Benali,Jimenez,Miranda,Tormos
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- Electron transfer in P450 mechanisms. Microsomal metabolism of cyclopropylbenzene and p-cyclopropylanisole
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The metabolism of cyclopropylbenzene (1a) and 4-cyclopropylanisole (1b) was studied using liver microsomal preparations from control, phenobarbital- and β-naphthoflavone treated rats. With all three types of microsomes 1a was metabolized by benzylic hydroxylation to give 1-phenylcyclopropanol and by aromatic hydroxylation at C-4; the former predominated by a factor of 2-4. BNF-induced microsomes also formed 2-cyclopropylphenol. No cyclopropyl ring-opened metabolites of 1a, including benzoic acid, were detected in any of the incubations. With PB-induced microsomes 1b underwent O-demethylation (90%) and benzylic hydroxylation; no other metabolites were detected. Progress curves for metabolism of 1a are markedly nonlinear after only limited conversion of substrate, suggesting the possibility that 1a, like other cyclopropyl compounds, could be a suicide substrate for one or more isozymes of P450. For both 1a and b, metabolite formation and enzyme inactivation can be explained by conventional P450 reaction mechanisms not involving electron abstraction.
- Riley,Hanzlik
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- Isomerization of 2-(2-propenoxy)phenyllithium: Tandem anionic cyclization-γ-elimination
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2-(2-Propenoxy)phenyllithium (1), which may be prepared from the corresponding iodide by low-temperature lithium-iodine exchange, rearranges on warming in the presence of TMEDA via 5-exo cyclization to (2,3-dihydrobenzofuranyl)methyllithium (2) followed by γ-elimination to give variable amounts of the lithium salt of 2-(cyclopropyl)phenol (3).
- Bailey, William F.,Punzalan, Eric R.
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- Direct hydroxylation of benzene and aromatics with H2O2 catalyzed by a self-assembled iron complex: Evidence for a metal-based mechanism
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An iminopyridine Fe(ii) complex, easily prepared in situ by self-assembly of cheap and commercially available starting materials (2-picolylaldehyde, 2-picolylamine, and Fe(OTf)2 in a 2 : 2 : 1 ratio), is shown to be an effective catalyst for the direct hydroxylation of aromatic rings with H2O2 under mild conditions. This catalyst shows a marked preference for aromatic ring hydroxylation over lateral chain oxidation, both in intramolecular and intermolecular competitions, as long as the arene is not too electron poor. The selectivity pattern of the reaction closely matches that of electrophilic aromatic substitutions, with phenol yields and positions dictated by the nature of the ring substituent (electron-donating or electron-withdrawing, ortho-para or meta-orienting). The oxidation mechanism has been investigated in detail, and the sum of the accumulated pieces of evidence, ranging from KIE to the use of radical scavengers, from substituent effects on intermolecular and intramolecular selectivity to rearrangement experiments, points to the predominance of a metal-based SEAr pathway, without a significant involvement of free diffusing radical pathways.
- Capocasa, Giorgio,Olivo, Giorgio,Barbieri, Alessia,Lanzalunga, Osvaldo,Di Stefano, Stefano
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- Diastereo- and enantioselective carbolithiation of allyl o-lithioaryl ethers. New chiral cyclopropane derivatives
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(matrix presented) Different allyl 2-lithioaryl ethers undergo a tandem carbolithiation/γ-elimination in Et2OH-MEDA affording o-cyclopropyl phenol or naphthol derivatives in a diastereoselective manner. The use of (-)-sparteine as a chiral liga
- Barluenga, Jose,Fananas, Francisco J.,Sanz, Roberto,Marcos, Cesar
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- Synthesis of spiro[26]nonadienones and spiro[3.6]decadienones by the reaction of cyclopropyl- and cyclobutylmagnesium carbenoids with lithium phenolates and naphtholates
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Treatment of 1-chlorocyclopropyl p-tolyl sulfoxides and 1-chlorocyclobutyl p-tolyl sulfoxides with a Grignard reagent at low temperature afforded cyclopropylmagnesium carbenoids and cyclobutylmagnesium carbenoids, respectively, via a sulfoxide-magnesium e
- Satoh, Tsuyoshi,Kimura, Tsutomu,Sasaki, Yuki,Nagamoto, Shinobu
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experimental part
p. 2091 - 2101
(2012/08/27)
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- Explorations of [4+2] and [5+2] cycloadditions of dienylcyclopropane derived enzymatically from cyclopropylbenzene
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Fermentation of cyclopropylbenzene with E. coli JM109(pDTG601a) furnished optically pure 1-cyclopropyl-2,3-dihydroxycyclohexa-4,6-diene whose reactivity in [4+2]- and [5+2]-cycloaddition chemistry was explored. Georg Thieme Verlag Stuttgart. New York.
- Hudlicky, Jason Reed,Hopkins-Hill, John,Hudlicky, Tomas
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supporting information; experimental part
p. 2891 - 2895
(2012/01/06)
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- 5H-PYRROLO[3,4-£>]PYRAZIN-7-AMINE DERIVATIVES INHIBITORS OF BETA-SECRETASE
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The present invention relates to novel compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Downs syndrome, β- amyloid angiopathy such as but not limited to cerebral amyloid angiopathy or hereditary cerebral hemorrhage, disorders associated with cognitive impairment such as but not limited to MCI ("mild cognitive impairment"), Alzheimer Disease, memory loss, attention deficit symptoms associated with Alzheimer disease, neurodegeneration associated with diseases such as Alzheimer disease or dementia including dementia of mixed vascular and degenerative origin, pre-senile dementia, senile dementia and dementia associated with Parkinson's disease, progressive supranuclear palsy or cortical basal degeneration.
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Page/Page column 43-44
(2011/02/24)
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- NEW COMPOUNDS 574
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The present invention relates to novel compounds of formula (I) and their pharmaceutical compositions. In addition, the present invention relates to therapeutic methods for the treatment and/or prevention of Aβ-related pathologies such as Downs syndrome,
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Page/Page column 27
(2010/06/13)
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- A novel synthesis of spiro[2.6]nonadienones by the reaction of magnesium cyclopropylidenes with naphtholates and phenolates
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The sulfoxide-magnesium exchange reaction of aryl 1-chlorocyclopropyl sulfoxides with i-PrMgCl in THF at low temperature gave magnesium cyclopropylidenes. Treatment of the magnesium cyclopropylidenes with lithium naphtholates or phenolates resulted in the formation of spiro[2.6]nonadienones in up to 82% yield. The structure of the spiro[2.6]nonadienones was found to be dependent on the structure of the naphtholates and phenolates.
- Satoh, Tsuyoshi,Nagamoto, Shinobu,Yajima, Masanobu,Yamada, Yukie,Ohata, Yuki,Tadokoro, Makoto
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p. 5431 - 5435
(2008/12/22)
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- AMINO-5-[SUBSTITUTED-4-(DIFLUOROMETHOXY)PHENYL]-5- PHENYLIMIDAZOLONE COMPOUNDS AS ?-SECRETASE INHIBITORS
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The present invention provides a 2-amino-5-[substituted-4-(difluoromethoxy)phenyl]-5-phenylimidazolone compound of formula (I) The present invention also provides methods for the use thereof to inhibit ?-secretase (BACE) and treat ?-amyloid deposits and neurofibrillary tangles.
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(2008/12/07)
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- Characterization of thyroid hormone receptor α (TRα)-specific analogs with varying inner- and outer-ring substituents
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Analogs of the TRα-specific thyromimetic CO23 were synthesized and analyzed in vitro using competitive binding and transactivation assays. Like CO23, all analogs bind to both thyroid hormone receptor subtypes with about the same affinity; however, modification of CO23 by derivatization of the 3′ position of the outer-ring or replacement of the inner-ring iodides with bromides attenuates binding. Despite lacking a preference in binding to TRα, all analogs display TRα-specificity in transactivation assays using U2OS and HeLa cells. At best, several agonists exhibit an approximately 6-12-fold preference in transactivation when tested with TRα in HeLa cells. One analog, CO24, showed in vivo TRα-specific action in a tadpole metamorphosis assay.
- Ocasio, Cory A.,Scanlan, Thomas S.
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p. 762 - 770
(2008/09/17)
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- Intramolecular carbolithiation of allyl o-lithioaryl ethers: A new enantioselective synthesis of functionalized 2,3-dihydrobenzofurans
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A new and easy method for the diastereoselective synthesis of 3-functionalized 2,3-dihydrobenzofuran derivatives from allyl 2-bromoaryl ethers is described. The key step of this transformation involves an intramolecular carbolithiation reaction of allyl 2-lithioaryl ethers. The substituents in both the allyl and the aryl moieties play an important and decisive role in stopping the reaction at the benzofuran thus avoiding a γ-elimination reaction. Finally, this process is amenable to the synthesis of enantiomerically enriched compounds by using ( - )-sparteine as a chiral inductor.
- Barluenga, Jose,Fananas, Francisco J.,Sanz, Roberto,Marcos, Cesar
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p. 5397 - 5407
(2007/10/03)
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- Enzymatic oxidation of cyclopropylbenzene: Structures of new metabolites and possible mechanistic implications
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Cyclopropylbenzene was subjected to whole-cell fermentation with either Escherichia coli JM109 (pDTG601) or E. coli JM109 (pDTG602), expressing toluene dioxygenase and toluene dioxygenase - dihydrodiol dehydrogenase enzymes, respectively. The corresponding metabolites, 3-cyclopropylcyclohexa-3,5-diene-1,2-diol (3) and 3-cyclopropylbenzene-1,2-diol (5) have been isolated in yields of 2.5 and 1 g L-1, respectively. The absolute stereochemistry correlation for 3 is provided, along with a preliminary discussion of its potential in asymmetric synthesis. Possible mechanistic implications are indicated for the enzymatic oxygenation through the use of calculations. Experimental data are provided for all new compounds.
- Bui, Vu P.,Nguyen, Minh,Hansen, Jeff,Baker, John,Hudlicky, Tomas
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p. 708 - 713
(2007/10/03)
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- On the Reactivity of o-Lithioaryl Ethers: Tandem Anion Translocation and Wittig Rearrangement
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(matrix presented) Allyl and benzyl 2-lithioaryl ethers, generated by bromine-lithium exchange in THF, undergo a new tandem anion translocation-[1,2]-Wittig rearrangement allowing the isolation of the corresponding benzylic alcohols.
- Barluenga, Jose,Fananas, Francisco J.,Sanz, Roberto,Marcos, Cesar,Trabada, Marta
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p. 1587 - 1590
(2007/10/03)
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- Lactone formation by rhodium-catalyzed C-C bond cleavage of cyclobutanone
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As a coordinating ligand, the phenol group in appropriately substituted cyclobutanones facilitates the Rh1-catalyzed activation of the C-C bond between the carbonyl group and the α-carbon atom. This novel reaction leads, depending on the position of the phenol group on the cyclobutanone ring, to lactones of varying ring size (for example, as shown for a seven-membered-ring lactone).
- Murakami, Masahiro,Tsuruta, Takuo,Ito, Yoshihiko
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p. 2484 - 2486
(2007/10/03)
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- 120. Stereoselective Ring Opening of Electronically Excited Cyclohexa-2,4-dienones: Cause and Effect
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The two conformers of a cyclohexa-2,4-dienone with different substituents at C(6) on irradiation are believed to undergo ring opening stereospecifically affording a mixture of two configurationally isomeric diene-ketenes (and descendents thereof). Exceptions are generally found for those dienones with one C and one O substituent or even with two C substituents, if one of them carries a polar group at a site able to interact through space with the ring C=O group. In these cases, only one of the two anticipated diene-ketenes (and descendents thereof) is produced. A thorough investigation of the photochemistry of a series of structurally different cyclohexa-2,4-dienones on analytical as well as on preparative scale extends our mechanistic knowledge of the various routes from diene-ketenes into a variety of compound classes. Novel compound classes accessible to diene-ketenes are seven-membered carbocycles (by intramolecular aldolization of the zwitterion of appropriately substituted, transiently formed diene-(N,O)-ketene acetals) and βlactams (by Staudinger reaction).
- Quikert, Gerhard,Scherer, Stefan,Reichert, Dietmar,Nestler, Hans-Peter,Wennemers, Helma,Ebel, Andreas,Urbahns, Klaus,Wagner, Klaus,Michaelis, Klaus-Peter,Wiech, Gerhard,Prescher, Günter,Bronstert, Bernd,Freitag, Bernd-Jürgen,Wicke, Ilka,Lisch, Dietmar,Belik, Pavel,Crecelius, Thorsten,H?rstermann, Dirk,Zimmermann, Gottfried,Bats, Jan W.,Dürner, Gerd,Rehm, Dieter
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p. 1683 - 1772
(2007/10/03)
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- Preparation, antimicrobial evaluation, and mutagenicity of [2- hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl]methanols, [5-tert-butyl-2- methylaminophenyl]-[1-methyl-5-nitro-1H-2-imidazolyl] methanol, and [2- hydroxyaryl]-[1-methyl-5-nitro-1H-2-imidazolyl] ketones
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Efficient preparations of the titled compounds are described, their antimicrobial activity and mutagenic properties being evaluated. Some of the studied compounds are nonmutagenic and present a MIC as low as some of the usual standards in the field.
- Arredondo,Moreno-Manas,Pleixats,Palacin,Raga,Castello,Ortiz
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p. 1959 - 1968
(2007/10/03)
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