- A photo-reagent system of benzimidazoline and Ru(bpy)3Cl 2 to promote hexenyl radical cyclization and Dowd-Beckwith ring-expansion of α-halomethyl-substituted benzocyclic 1-alkanones
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A combination of 2-aryl substituted 1,3-dimethyl-benzimidazolines (DMBIHs) and tris(2,2′-bipyridine)ruthenium(II) chloride, Ru(bpy) 3Cl2 was used to promote photoinduced electron-transfer (PET) reactions of α-halomethyl-substituted benzocyclic 1-alkanones. This photo-reagent system stimulates free radical forming, cleavage of both carbon-bromine and carbon-chlorine bonds that are not activated by carbonyl groups. The resulting free radicals undergo 5-exo hexenyl cyclization as well as sequential cyclization and ring-expansion (Dowd-Beckwith) reactions to form radicals that abstract hydrogen atoms from the radical cation of DMBIH to yield the observed products. The results of a study of the effects of substituents located on the 2-aryl ring of DMBIH suggest that steric and hydrogen-bonding interactions influence the nature of the reaction pathways followed by the radical intermediates. PET reactions using an iridium complex and DMBIH were also investigated.
- Hasegawa, Eietsu,Tateyama, Minami,Hoshi, Tsuneaki,Ohta, Taku,Tayama, Eiji,Iwamoto, Hajime,Takizawa, Shin-Ya,Murata, Shigeru
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Read Online
- Rapid Enantioselective and Diastereoconvergent Hybrid Organic/Biocatalytic Entry into the Oseltamivir Core
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A formal synthesis of the antiviral drug (-)-oseltamivir (Tamiflu) has been accomplished starting from m-anisic acid via a dissolving metal or electrochemical Birch reduction. The correct absolute stereochemistry is efficiently set through enzyme-catalyzed carbonyl reduction on the resultant racemic α,β-unsaturated ketone. A screen of a broad ketoreductase (KRED) library identified several that deliver the desired allylic alcohol with nearly perfect facial selectivity at the new center for each antipodal substrate, indicating that the enzyme also is able to completely override inherent diastereomeric bias in the substrate. Conversion is complete, with d-glucose serving as the terminal hydride donor (glucose dehydrogenase). For each resulting diastereomeric secondary alcohol, O/N-interconversion is then efficiently effected either by synfacial [3,3]-sigmatropic allylic imidate rearrangement or by direct, stereoinverting N-Mitsunobu chemistry. Both stereochemical outcomes have been confirmed crystallographically. The α,β-unsaturation is then introduced via an α-phenylselenylation/oxidation/pyrolysis sequence to yield the targeted (S)-N-acyl-protected 5-amino-1,3-cyclohexadiene carboxylates, key advanced intermediates for oseltamivir pioneered by Corey (N-Boc) and Trost (N-phthalamido), respectively.
- Tiwari, Virendra K.,Powell, Douglas R.,Broussy, Sylvain,Berkowitz, David B.
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supporting information
p. 6494 - 6503
(2021/05/06)
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- Phosphinous Acid Platinum Complex as Robust Catalyst for Oxidation: Comparison with Palladium and Mechanistic Investigations
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Secondary phosphine oxides proved to be effective preligands to stabilise a hydroxy-platinum based catalyst that allows the aerobic/anaerobic oxidation of challenging substrates. Kinetic comparisons showed that this system is more efficient and stable than previously reported similar palladium-based catalysts. A neutral platinum dimer bearing bridging hydroxy ligands has been isolated and fully characterised by X-ray diffraction and its involvement in the mechanism has been evidenced by mechanistic studies.
- Membrat, Romain,Vasseur, Alexandre,Martinez, Alexandre,Giordano, Laurent,Nuel, Didier
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supporting information
p. 5427 - 5434
(2018/10/20)
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- Synthesis of gem-difluorocyclopentane/hexane building blocks
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An approach to the preparation of gem-difluorocyclopentane/hexane-derived carboxylic acids and amines is described. Whereas for 3,3-difluoro-substituted cycloalkanones, straightforward deoxofluorination of the corresponding ketoesters led to the target compounds, in the case of 2,2-difluoro isomers, the bypass or alternative routes were necessary.
- Melnykov, Kostiantyn P.,Nosik, Pavel S.,Kurpil, Bohdan B.,Sibgatulin, Dmitriy A.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.
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- Biocatalytic synthesis of chiral cyclic γ-oxoesters by sequential C-H hydroxylation, alcohol oxidation and alkene reduction
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A three-step biocatalytic procedure is described for the conversion of methyl and ethyl cyclopentene- and cyclohexenecarboxylates into both the enantiomers of the corresponding chiral 3-oxoesters, which are useful building blocks for the synthesis of active pharmaceutical ingredients. The allylic hydroxylation of the starting cycloalkenecarboxylates is carried out by using R. oryzae resting cells entrapped in alginate beads, in acetate buffer solution at 25 °C. The oxidation of the intermediate allylic alcohols to unsaturated ketones, performed by the laccase/TEMPO system, and the ene-reductase mediated hydrogenation of the alkene bond were carried out in the same reaction vessel in a sequential mode at 30 °C. Being entirely biocatalytic, our multistep procedure provides considerable advantages in terms of selectivity and environmental impact over reported chemical methods.
- Brenna, Elisabetta,Crotti, Michele,Gatti, Francesco G.,Monti, Daniela,Parmeggiani, Fabio,Pugliese, Andrea,Tentori, Francesca
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p. 5122 - 5130
(2017/11/09)
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- Small Molecule Reversible Inhibitors of Bruton's Tyrosine Kinase (BTK): Structure-Activity Relationships Leading to the Identification of 7-(2-Hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide (BMS-935177)
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Bruton's tyrosine kinase (BTK) belongs to the TEC family of nonreceptor tyrosine kinases and plays a critical role in multiple cell types responsible for numerous autoimmune diseases. This article will detail the structure-activity relationships (SARs) leading to a novel second generation series of potent and selective reversible carbazole inhibitors of BTK. With an excellent pharmacokinetic profile as well as demonstrated in vivo activity and an acceptable safety profile, 7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxo-3,4-dihydroquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide 6 (BMS-935177) was selected to advance into clinical development.
- De Lucca, George V.,Shi, Qing,Liu, Qingjie,Batt, Douglas G.,Beaudoin Bertrand, Myra,Rampulla, Rick,Mathur, Arvind,Discenza, Lorell,D'Arienzo, Celia,Dai, Jun,Obermeier, Mary,Vickery, Rodney,Zhang, Yingru,Yang, Zheng,Marathe, Punit,Tebben, Andrew J.,Muckelbauer, Jodi K.,Chang, Chiehying J.,Zhang, Huiping,Gillooly, Kathleen,Taylor, Tracy,Pattoli, Mark A.,Skala, Stacey,Kukral, Daniel W.,McIntyre, Kim W.,Salter-Cid, Luisa,Fura, Aberra,Burke, James R.,Barrish, Joel C.,Carter, Percy H.,Tino, Joseph A.
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p. 7915 - 7935
(2016/10/12)
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- 9H-Carbazole-1-carboxamides as potent and selective JAK2 inhibitors
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The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
- Zimmermann, Kurt,Sang, Xiaopeng,Mastalerz, Harold A.,Johnson, Walter L.,Zhang, Guifen,Liu, Qingjie,Batt, Douglas,Lombardo, Louis J.,Vyas, Dinesh,Trainor, George L.,Tokarski, John S.,Lorenzi, Matthew V.,You, Dan,Gottardis, Marco M.,Lippy, Jonathan,Khan, Javed,Sack, John S.,Purandare, Ashok V.
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p. 2809 - 2812
(2015/06/08)
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- IRAK INHIBITORS AND USES THEREOF
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The present invention provides arylo-fused thienopyrimidine compounds, compositions thereof, and methods of using the same.
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Paragraph 00284-00285
(2014/02/15)
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- FLT3 INHIBITORS AND USES THEREOF
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The present invention provides methods of using compounds of formula I: or compositions thereof for the inhibition of FLT3, and the treatment of FLT3-mediated disorders.
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Paragraph 00353; 00356
(2014/12/12)
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- Photoinduced electron transfer promoted radical ring expansion and cyclization reactions of α-(ω-carboxyalkyl) β-keto esters
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Photoinduced electron transfer (PET) promoted decarboxylation of α-(ω-carboxyalkyl) β-keto esters undergoes radical ring expansion and cyclization reactions. This mild and environmentally friendly method can provide one-carbon expanded γ-keto esters and b
- Nishikawa, Keisuke,Ando, Tomoki,Maeda, Kousuke,Morita, Toshio,Yoshimi, Yasuharu
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supporting information
p. 636 - 638
(2013/04/10)
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- SPIROLACTAM DERIVATIVES AND USES OF SAME
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The present invention provides spirolactam derivatives of formula (I): wherein R1-R7 are as defined herein; or a pharmaceutically acceptable salt thereof; and pharmaceutical compositions and uses of the same.
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Page/Page column 23
(2011/05/05)
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- Eco-friendly molecular transformations catalyzed by a vitamin B 12 derivative with a visible-light-driven system
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A new bio-inspired system composed of a vitamin B12 derivative and Rose Bengal, catalyzed the dehalogenations of various toxic alkyl halides such as 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) via a noble-metal-free and visible-light-driven process. This system also catalyzed radical-involved organic reactions such as the 1,2-migration of acyl group via a tin-free process. The Royal Society of Chemistry.
- Tahara, Keishiro,Hisaeda, Yoshio
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supporting information; experimental part
p. 558 - 561
(2011/05/08)
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- Green molecular transformation by a B12-TiO2 hybrid catalyst as an alternative to tributyltin hydride
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The B12-TiO2 hybrid catalyst was effectively used for the radical reactions, such as 1,2-migrations of phenyl groups and acyl groups under irradiation by UV light, and the selectivity of the reaction was controlled by the solvent system.
- Shimakoshi, Hisashi,Abiru, Makoto,Izumi, Shin-Ichiro,Hisaeda, Yoshio
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scheme or table
p. 6427 - 6429
(2010/03/04)
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- Facile Ring Expansions of α-Halomethyl β-Keto Esters Mediated with SmI2
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Treatment of α-halomethyl β-keto esters with SmI2 afforded their corresponding one-carbon expanded products with the aids of HMPA or NiI2.
- Chung, So Hee,Cho, Min Seok,Choi, Jun Young,Kwon, Doo Won,Kim, Yong Hae
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p. 1266 - 1268
(2007/10/03)
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- Reductive transformation of α β-epoxy ketones and other compounds promoted through photoinduced electron transfer processes with 1,3-dimethyl- 2-phenylbenzimidazoline (DMPBI)
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Photoreactions of epoxy ketones, aromatic ketones, haloketones, and aromatic halides with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI) were studied. Photoinduced single-electron transfer from DMPBI to such substrates initiates the reactions, followed by radical rearrangement and reduction to finally give several reduced products in modest to good yields.
- Hasegawa, Eietsu,Yoneoka, Akira,Suzuki, Kumiko,Kato, Teru,Kitazume, Takashi,Yanagi, Kazuhiro
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p. 12957 - 12968
(2007/10/03)
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- First example of samarium diiodide-promoted sequential cyclization and ring-expansion reactions of α-bromomethyl cyclic β-keto esters to homologated γ-keto esters
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SmI2 reductions of some aromatic as well as aliphatic α-bromomethyl cyclic β-keto esters produced one-carbon homologated γ-keto esters in modest to good yields.
- Hasegawa, Eietsu,Kitazume, Takashi,Suzuki, Kimiko,Tosaka, Emi
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p. 4059 - 4062
(2007/10/03)
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- Hetrazepine compounds which have useful pharmaceutical utility
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The invention relates to new hetrazepines of general formula STR1 wherein A, Z, n, X, Y, R 1, R 2, R 3 and R 4 have the meanings given in the specification.The new compounds are intended for use in treating pathological conditions and diseases in which PAF (platelet activating factor) is implicated.
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- Electroorganic Chemistry. 124. Electroreductive Intramolecular Coupling of α-(ω-Bromoalkyl) β-Keto Esters
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Intramolecular coupling occurs when cyclic α-(bromomethyl) β-keto esters are electrochemically reduced in the presence of trimethylsilyl chloride and one-carbon ring-enlarged products are obtained in reasonable yields.Electroreduction of α-(γ-bromopropyl) β-keto esters also affords the corresponding five-membered cyclized products and/or the corresponding ring-opened compounds.The ease of ring opening of the cyclized products is highly influenced by their stereoconfiguration.Electroreduction of α-(β-bromoethyl) β-keto ester gives the product formed by the reductive elimination of the bromoethyl group whereas α-(δ-bromobutyl) β-keto ester yields the product of the reductive elimination of bromine.This electroreductive intramolecular coupling is initiated by the reduction of the carbon-bromine bond and proceeds through a carbanion intermediate.
- Shono, Tatsuya,Kise, Naoki,Uematsu, Nobuyuki,Morimoto, Shinji,Okazaki, Eiichi
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p. 5037 - 5041
(2007/10/02)
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- Process for preparing cyclohexanonecarboxylic acid compounds
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A process for preparing cyclohexanonecarboxylic acid compounds by catalytically hydrogenating the corresponding hydroxybenzoic acid compounds in a secondary alcohol or tertiary alcohol solvent.
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- Enzymatic in vitro Reduction of Ketones. Part 13. Horse Liver Alcohol Dehydrogenase (HLAD) as a Tool for the Synthesis of Enantiomerically Pure Alkyl 3-oxo- and 3-hydroxycyclohexanecarboxylates.
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Enantiomerically pure alkyl 3-oxocyclohexanecarboxylates and the corresponding alcohols have been prepared using HLAD as a suitable catalyst.Kinetic and thermodynamic parameters for the enzymatic reductions are given.The enantiomeric purity and the absolute configuration of the reaction products are determined.The alcohol moiety (methyl, isopropyl or pentyl) of the ester group influences both the steric course and the kinetics of the reduction.Side reactions of the substrate with the reaction medium can be avoided by an appropriate choice of the reaction conditions.
- Willaert, J. J.,Lemiere, G. L.,Dommisse, R. A.,Lepoivre, J. A.,Alderweireldt, F. C.
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p. 2401 - 2423
(2007/10/02)
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- Synthesis of aminoiderivatives of 4,5,6,7-tetrahydro-benzothiazole. II. 4, 5 and 6-aminomethyl derivatives with cardiovascular activity
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The ethyl esters of 4,5,6,7-tetrahdyro-benzothiazolyl-4 carboxylic acids were synthesized from corresponding ethyl 1-oxo-2 bromo-cyclohexane-carboxylates. Their reduction to alcohols, which were then transformed into tosylates, leads to the aminomethyl derivatives. These derivatives are practically devoid of antihistaminic H2 and dopaminergic activities but have interesting cardiovascular properties.
- Maillard,Delaunay,Langlois,et al.
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p. 457 - 460
(2007/10/02)
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