- Asymmetric one-pot synthesis of five- and six-membered lactones via dynamic covalent kinetic resolution: Exploring the regio- and stereoselectivities of lipase
-
Cascade lipase-catalyzed lactonization has been applied to dynamic hemithioacetal formation, leading to efficient five- and six-membered lactone synthesis as well as chiral discrimination. Solvent-dependent regioselectivity was observed for the selective formation of 1,3-oxathiolan-5-one and γ-butyrolactone derivatives.
- Xu, Jintao,Hu, Lei
-
-
Read Online
- Synthesis of substituted γ- and δ-lactams through Mannich-type reactions of solid-supported N-acyliminium ions
-
We report the results of our recent investigations into the reactivity of cyclic solid-supported N-acyliminium ions. An intermolecular Mannich-type transformation of these intermediates was used to generate libraries of substituted lactams. Masked aldehyde building blocks were readily prepared and coupled to peptides immobilized on PEGA800(polyethylene glycol dimethyl acrylamide) resin through an HMBA [4-(hydroxymethyl)benzoic acid] linker. When treated with acid, the aldehyde was cleanly released and condensed with the amide backbone to form a hydroxylactam/N-acyliminium ion, which underwent intermolecular reactions with a series of nucleophilic heterocycles, such as substituted indoles, thiophenes, furans, and electron-rich benzenes. The resulting lactams were formed within a few minutes and in high purities (typically >85 %). A new and efficient method for the solid-phase synthesis of diversely substituted γ- and δ-lactams through Mannich-type reactions of cyclic N-acyliminium ions is presented. A wide range of external aromatic and heteroaromatic carbon nucleophiles could be successfully used in the sequence.
- Komnatnyy, Vitaly V.,Taveras, Kennedy M.,Nandurkar, Nitin S.,Le Quement, Sebastian T.,Givskov, Michael,Nielsen, Thomas E.
-
-
Read Online
- A mild and efficient Nef reaction for the conversion of nitro to carbonyl group by dimethyldioxirane (DMD) oxidation of nitronate anions
-
DMD oxidation of nitronate onions, generated in situ from the corresponding nitroalkanes, affords the corresponding carbonyl products. Highest yields were obtained when one equivalent of water was added before the oxidation with DMD.
- Adam, Waldemar,Makosza, Mieczyslaw,Saha-M?ller, Chantu R.,Zhao, Cong-Gui
-
-
Read Online
- STEREOSPECIFIC CONSTRUCTION OF EXO-TETRASUBSTITUTED OLEFINS. THE EFFICIENT SYNTHESIS OF CYANO-CARBACYCLINS
-
Cyano-carbacyclins (2 and 3) were efficiently sythesized using the stereospecific 1,4-hydrogenation of the corresponding conjugated diene 10a catalyzed by the arene.Cr(CO)3 complex as a key step.
- Shibasaki, Masakatsu,Sodeoka, Mikiko
-
-
Read Online
- A new, highly selective, water-soluble rhodium catalyst for methyl acrylate hydroformylation
-
Hydroformylation of methylacrylate to α-aldehyde can be achieved in a two-phase system in the presence of two new water-soluble phosphines.High yields and selectivities of α-aldehyde (ca. 80percent with a α/β ratio of 1:20) were obtained.Spectroscopic studies have been carried out and some new rhodium complexes formed in situ in catalytic systems have been identified.Keywords: Hydroformylation; Methyl acrylate; Water-soluble phosphines; Rhodium; Catalysis; Two phase system
- Fremy, Georges,Castanet, Yves,Grzybek, Ryszard,Minflier, Eric,Mortreux, Andre,et al.
-
-
Read Online
- New Reagents for the Regiospecific Synthesis of Naturally Occurring Quinizarins
-
A modified Nef reaction applied to 4-nitrobutanoates gives the corresponding acetals which after hydrolysis and enol silylation yield the new 1,3-dienes 1-methoxy-1,4-bis(trimethylsiloxy)butadiene and its 3-methyl derivative.The latter reacts smoothly with chloronaphthoquinones and provides simple and efficient syntheses of 2-methylquinizarin, islandicin, digitopurpone, and erythroglaucin.
- Simoneau, Bruno,Savard, Jacques,Brassard, Paul
-
-
Read Online
- Synthesis of Optically Active Maresin 2 and Maresin 2 n-3 DPA
-
Maresins are among the most potent antiinflammatory lipid metabolites. We report stereoselective syntheses of maresin 2 and maresin 2 n-3 DPA. The anti -diol was constructed through epoxide ring opening of an optically active β,γ-epoxy aldehyde, synthesized in situ by Swern oxidation of the corresponding alcohol. Finally, the target compounds were synthesized through a Sonogashira coupling of a C9-C22 iodide and methyl (Z)-oct-4-en-7-ynoate or methyl oct-7-ynoate, respectively.
- Ogawa, Narihito,Amano, Takahito,Kobayashi, Yuichi
-
supporting information
p. 295 - 298
(2020/11/18)
-
- NEW COMPOUNDS FOR TREATMENT OF DISEASES RELATED TO DUX4 EXPRESSION
-
The present invention relates to compounds for the treatment of diseases related to DUX4 expression, such as muscular dystrophies. It also relates to use of such compounds, or to methods of use of such compounds.
- -
-
Page/Page column 58; 86
(2021/06/04)
-
- Total Synthesis of DHA and DPA n-3Non-Enzymatic Oxylipins
-
Oxylipins are formed in vivo from polyunsaturated fatty acids (PUFAs). A large structural variety of compounds is grouped under the term oxylipins, which differ from their formation mechanism (involving enzymes or not), as well as their chemical structures (cyclopentane, tetrahydrofuran, hydroxylated-PUFA, etc.). All structures of oxylipins are of great biological interest. Directly correlated to oxidative stress phenomenon, non-enzymatic oxylipins are used as systemic and/or specific biomarkers in various pathologies, and more especially, they were found to have their own biological properties. Produced in vivo as a non-separable mixture of isomers, their total synthesis is a keystone to answer biological questions. In this work, the total synthesis of three non-enzymatic oxylipins derived from docosahexaenoic acid (DHA) and docosapentanoic acid (DPAn-3) is described using a unique and convergent synthetic strategy.
- Bultel-Poncé, Valérie,Degrange, Thomas,Durand, Thierry,Galano, Jean-Marie,Guy, Alexandre,Merad, Jérémy,Oger, Camille,Reversat, Guillaume
-
-
- Catalyst composition containing bidentate phosphine ligand and application thereof
-
The catalyst composition comprises a bidentate phosphine ligand and a rhodium complex, wherein the skeleton of the bidentate phosphine ligand not only has C. 2 The symmetry and the appropriate rigidity, and the phosphine ligand derived based on the skeleton can provide effective steric hindrance around the catalyst center metal, so that the selectivity of the catalyst can be remarkably improved, the aldehyde yield is not lower 92% when the catalyst combination is applied to the hydroformylation reaction, and the selectivity of n-aldehyde is not lower 90%. In addition, the raw materials olefins with different structures can obtain outstanding reaction rate and normal aldehyde selectivity as compared with the existing catalyst systems, and can be suitable for the hydroformylation reaction of more types of olefins.
- -
-
Paragraph 0068; 0089-0092
(2021/11/03)
-
- CRYSTAL FORM I OF A 5-AMINOPYRAZOLE CARBOXAMIDE COMPOUND AS BTK INHIBITOR
-
Disclosed is a new crystal form of a 5-aminopyrazole carboxamide compound as shown in Formula (I). Also disclosed are a preparation method for said crystal form of said compound, a pharmaceutical composition of said crystal form of said compound, and uses thereof.
- -
-
Paragraph 0036-0037; 0039
(2020/09/23)
-
- AMINOPEPTIDASE A INHIBITORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
-
The present invention relates to a novel compound, to a composition comprising the same, to methods for preparing the compound, and the use of this compound in therapy. In particular, the present invention relates to compound that is useful in the treatment and prevention of primary and secondary arterial hypertension, ictus, myocardial ischaemia, cardiac and renal insufficiency, myocardial infarction, peripheral vascular disease, diabetic proteinuria, Syndrome X and glaucoma.
- -
-
Page/Page column 32
(2020/06/10)
-
- Photoredox-Catalyzed Isomerization of Highly Substituted Allylic Alcohols by C?H Bond Activation
-
Photoredox-catalyzed isomerization of γ-carbonyl-substituted allylic alcohols to their corresponding carbonyl compounds was achieved for the first time by C?H bond activation. This catalytic redox-neutral process resulted in the synthesis of 1,4-dicarbonyl compounds. Notably, allylic alcohols bearing tetrasubstituted olefins can also be transformed into their corresponding carbonyl compounds. Density functional theory calculations show that the carbonyl group at the γ-position of allylic alcohols are beneficial to the formation of their corresponding allylic alcohol radicals with high vertical electron affinity, which contributes to the completion of the photoredox catalytic cycle.
- Guo, Kai,Huang, Jun,Li, Anding,Li, Yuanhe,Yang, Zhen,Zhang, Zhongchao
-
supporting information
p. 11660 - 11668
(2020/05/25)
-
- Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
-
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ- or δ,δ-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
- Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
-
-
- Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
-
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η 3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ-or ?,?-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
- Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
-
p. 10048 - 10059
(2019/07/04)
-
- 5-AMINOPYRAZOLE CARBOXAMIDE DERIVATIVE AS BTK INHIBITOR AND PREPARATION METHOD AND PHARMACEUTICAL COMPOSITION THEREOF
-
The present application discloses novel 5-aminopyrazole carboxamide compounds as shown in formula (I), and stereoisomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof. In addition, the present application further discloses a method for the preparation of the compounds, a pharmaceutical composition comprising a compound of the invention and the use of the compounds.
- -
-
Paragraph 0082
(2019/04/16)
-
- ORGANIC ELECTROLUMINESCENT MATERIALS AND DEVICES
-
A compound having a structure of the formula Ir(LA)(LB), in which LA is a bidentate, tridentate, tetradentate, pentadentate, or hexadentate ligand and LB is a monodentate, bidentate, tridentate, or tetradentate ligand, or not present, and where the total denticity of LA plus LB is 6, and LA includes at least one structure of Formula I: is disclosed as a useful phosphorescent emitter compound.
- -
-
Paragraph 0153; 0155
(2019/02/25)
-
- Hydroformylation of unsaturated esters and 2,3-dihydrofuran under solventless conditions at room temperature catalysed by rhodium: N-pyrrolyl phosphine catalysts
-
Rhodium complexes of the type HRh(CO)L3 (where L is an N-pyrrolyl phosphine, such as P(NC4H4)3, PPh(NC4H4)2, or PPh2(NC4H4)) were applied in the hydroformylation of less reactive unsaturated substrates, namely allyl acetate, butyl acrylate, methyl acrylate, 2,3-dihydrofuran and vinyl acetate. Even at room temperature, these catalysts enabled complete substrate conversion and high chemoselectivity towards the corresponding aldehydes. High conversion of vinyl acetate (88% in 6 h) to the branched aldehyde was obtained with HRh(CO)[P(NC4H4)3]3 at 25 °C. An increase of the turnover frequency, TOF, up to 2000 mol mol-1 h-1 was achieved in this reaction under 20 bar of syngas (H2/CO = 1) at 80 °C. The introduction of chiral phosphines, BINAP or Ph-BPE, to this system resulted in the production of a branched aldehyde with enantioselectivity, ee, up to 44 and 81%, respectively. High activity combined with high enantioselectivity was achieved due to the formation of the mixed rhodium hydrides HRh(CO)[P(NC4H4)3](BINAP) and HRh(CO)[P(NC4H4)3](Ph-BPE), identified by the NMR method.
- Alsalahi,Trzeciak
-
p. 16990 - 16999
(2019/11/14)
-
- Glutarimide Alkaloids Through Multicomponent Reaction Chemistry
-
A concise four step synthetic route for glutarimide alkaloids of high biological interest is presented. The scaffold is accessed via an Ugi four component reaction, hereby introducing two points of variation. This is followed by a hydrolysis, a cyclization under mild conditions, and an amine deprotection. The diastereomers of the cyclized intermediate can be easily separated, thus leading to optically pure alkaloids. By this route, four natural products and ten derivatives were synthesized. The scope and limitations of the synthetic methodology were investigated.
- Konstantinidou, Markella,Kurpiewska, Katarzyna,Kalinowska-T?uscik, Justyna,D?mling, Alexander
-
supporting information
p. 6714 - 6719
(2018/11/25)
-
- Synthesis of Highly Oxygenated Carbocycles by Stereoselective Coupling of Alkynes to 1,3- and 1,4-Dicarbonyl Systems
-
Densely substituted and highly oxygenated carbocycles are challenging targets for synthesis. In particular, those possessing numerous contiguous, fully substituted carbon atoms (i.e., tertiary alcohols and quaternary centers) are often not accessible in a direct fashion, necessitating the strategic decoupling of ring-formation from the establishment of functionality about the system. Here, we describe an approach to the construction of highly oxygenated mono-, di-, and polycyclic carbocycles from the reaction of disubstituted alkynes with β- or γ-dicarbonyl systems. These processes embrace a variant of metallacycle-mediated annulation chemistry where initial alkyne-carbonyl coupling is followed by a second, now intramolecular, stereoselective C-C bond-forming event. In addition to revealing the basic reactivity pattern in intermolecular settings, we demonstrate that this class of reactivity is quite powerful in a fully intramolecular context and, when terminated by a stereoselective oxidation process, can be used to generate polycyclic systems containing a fully substituted and highly oxygenated five-membered ring.
- Kier, Matthew J.,Leon, Robert M.,O'Rourke, Natasha F.,Rheingold, Arnold L.,Micalizio, Glenn C.
-
supporting information
p. 12374 - 12377
(2017/09/23)
-
- Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines
-
A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound. A variety of 11 different electron-poor and electron-rich aryl aldehydes were screened to give trans-aziridines in 73-90% yield with 82-99% ee and trans/cis selectivities of 19:1 to >99:1. The optimal protocol for the trans-aziridination of aliphatic aldehydes did not require prereaction of the catalyst, aldehyde, and amine, and instead, the diazo compound could be added directly. The scope of the reaction is limited to unbranched aliphatic aldehydes and was tolerant of a number of functional groups including ethers, esters, epoxides, carbamates, and phthalimides. A total of 10 aliphatic aldehydes were examined and found to give trans-aziridines in 60-88% yield with 60-98% ee and trans/cis selectivities of 6:1 to >99:1. Alkenyl aldehydes did not react, but an alkynyl aldehyde gave a 71% yield and 95% ee of an aziridine that was found to be the cis- and not the trans-diastereomer. The aryl and aliphatic aldehydes both gave the trans-aziridines with the same absolute configuration with the same catalyst; however, in those cases where cis-aziridines were formed, the configuration was opposite for those formed from aryl versus aliphatic aldehydes.
- Zhou, Yubai,Gupta, Anil K.,Mukherjee, Munmun,Zheng, Li,Wulff, William D.
-
p. 13121 - 13140
(2017/12/26)
-
- (phenoxy)alkoxy-1H-indole derivatives or pharmaceutically acceptable salts thereof, preparation method therof and pharmaceutical composition for use in preventing or treating PPARα, PPARγ and PPARδ related diseases containing the same as an active ingredient
-
The present invention relates to (phenoxy)alkoxy-1H-indole derivatives or pharmaceutically allowable salts thereof, to a manufacturing method thereof, and to a pharmaceutical composition for preventing or treating PPARandalpha;, PPARandgamma; and PPARanddelta;-related diseases comprising the derivatives or salt thereof as an active ingredient. The (phenoxy)alkoxy-1H-indole derivatives have excellent abilities of activating PPARandalpha;, PPARandgamma; and PPARanddelta;, thereby being used for preventing or treating PPARandalpha;, PPARandgamma; and PPARanddelta;-related diseases of metabolic diseases, cardiovascular system diseases, cancer, inflammation, etc. as a PPAR agonist.COPYRIGHT KIPO 2017
- -
-
Paragraph 0247-0278
(2017/08/10)
-
- Selective hydroformylation of alkyl acrylates using [2,2′-bis(dipyrrolylphosphinooxy)-1,1′-(±)-binaphthyl]/Rh catalyst: reversal of regioselectivity
-
The rhodium-catalyzed hydroformylation of alkyl acrylates with different P-N diphosphine ligands is investigated here. Under mild conditions (syngas pressure: 2 MPa, 20 °C), 2,2′-bis(dipyrrolylphosphinooxy)-1,1′-(±)-binaphthyl (L1) rhodium catalyst could give good conversion of ethyl acrylate (82.9%) in 12 h and exclusive branched aldehyde selectivity of >99.0%. More importantly, on elevating the temperature to 90 °C, this Rh system could preferentially afford the linear aldehyde with 96.1% regioselectivity, and the TOF could reach up to 9000 h?1. Deuterioformylation was conducted to explore the mechanism of regioselectivity reversal, and the results established that the reversible rhodium hydride addition to form the Rh-alkyl species might play a vital role in this reversal. The β-hydride elimination of branched Rh-alkyl species was comparatively stronger than that of linear ones under increased temperature, probably because L1 could cause comparatively larger steric repulsion in branched Rh-alkyl species under high temperature, due to its bulky and rigid binaphthyl backbone characteristics. In turn, the linear Rh-alkyl species progress to linear aldehyde was facilitated.
- Shu, Xiao,Liang, Haoran,Wu, Qianhui,Zhou, Fanding,Zheng, Xueli,Fu, Haiyan,Xu, Bin,Li, Ruixiang,Zhang, Chunchun,Chen, Hua
-
p. 14816 - 14823
(2017/03/16)
-
- Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes
-
N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.
- Haghshenas, Pouyan,Gravel, Michel
-
supporting information
p. 4518 - 4521
(2016/09/28)
-
- α-Amino Acid-Isosteric α-Amino Tetrazoles
-
The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
- Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
-
supporting information
p. 3009 - 3018
(2016/03/26)
-
- Design, synthesis, and biological evaluation of a series of alkoxy-3-indolylacetic acids as peroxisome proliferator-activated receptor γ/δ agonists We dedicate this article to Professor Young-Ger Suh on the occasion of his retirement.
-
Abstract A series of alkoxy-3-indolylacetic acid analogs has been discovered as peroxisome proliferator-activated receptor (PPAR) agonists. Structure-activity relationship study indicated that PPARα/γ/δ activities were dependent on the nature of the hydrophobic group, the attachment position of the alkoxy linker to the indole ring, and N-alkylation of indole nitrogen. Some compounds presented significant PPARγ/δ activity and molecular modeling suggested their putative binding modes in the ligand binding domain of PPARγ. Of these, compound 51 was selected for in vivo study via an evaluation of microsomal stability in mouse and human liver. Compound 51 lowered the levels of fasting blood glucose, insulin, and HbA1c without gain in body weight in db/db mice. When compound 51 was treated, hepatic triglycerides level and the size of adipocytes in white adipose tissue of db/db mice were also reduced as opposed to treatment with rosiglitazone. Taken together, compound 51 shows high potential warranting further studies in models for diabetes and related metabolic disorders and may be in use as a chemical tool for the understanding of PPAR biology.
- Gim, Hyo Jin,Li, Hua,Jeong, Ji Hye,Lee, Su Jeong,Sung, Mi-Kyung,Song, Mi-Young,Park, Byung-Hyun,Oh, Soo Jin,Ryu, Jae-Ha,Jeon, Raok
-
supporting information
p. 3322 - 3336
(2015/08/03)
-
- Compound And Method
-
A compound of formula (I): (I) wherein Y is, Z is OR10, NR11R11 SR11, S(0)R11 S02R11, R10 is H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, CO—R11, or a protecting group, and R11 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or alkoxyl; a process for making a compound of formula (I); and a process for making a prostaglandin or a prostaglandin analogue using a compound of formula (I). wherein Y is
- -
-
Paragraph 0610-0615
(2015/06/17)
-
- Stereocontrolled total syntheses of optically active furofuran lignans
-
Plant products (+)-sesamin, (+)-sesaminol, (+)-methylpiperitol, (+)-aschantin, and (+)-5'-hydroxymethylpiperitol were synthesized in a highly stereocontrolled manner through l-proline-catalyzed bifunctional-urea-accelerated cross-aldol reaction, followed by biomimetic construction of the furofuran lignan skeleton through a quinomethide intermediate.
- Inai, Makoto,Ishikawa, Ryo,Yoshida, Naoto,Shirakawa, Nana,Akao, Yusuke,Kawabe, Yusuke,Asakawa, Tomohiro,Egi, Masahiro,Hamashima, Yoshitaka,Kan, Toshiyuki
-
p. 3513 - 3521
(2015/11/17)
-
- Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1
-
The total synthesis of the potent anti-inflammatory lipid mediator Protectin D1 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C10 and C17 were obtained via a chiral pool strategy from (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane and 3,4-O-isopropylidene-2-deoxy-d-ribose, respectively. Wittig reactions, Takai olefination, Pd0/CuISonogashira coupling, and Zn(Cu/Ag) reduction completed the total synthesis of Protectin D1.
- Rodriguez, Ana R.,Spur, Bernd W.
-
p. 6011 - 6015
(2014/12/11)
-
- Chroman-4-one- and chromone-based sirtuin 2 inhibitors with antiproliferative properties in cancer cells
-
Sirtuins (SIRTs) catalyze the NAD+-dependent deacetylation of Nε-acetyl lysines on various protein substrates. SIRTs are interesting drug targets as they are considered to be related to important pathologies such as inflammation and aging-associated diseases. We have previously shown that chroman-4-ones act as potent and selective inhibitors of SIRT2. Herein we report novel chroman-4-one and chromone-based SIRT2 inhibitors containing various heterofunctionalities to improve pharmacokinetic properties. The compounds retained both high SIRT2 selectivity and potent inhibitory activity. Two compounds were tested for their antiproliferative effects in breast cancer (MCF-7) and lung carcinoma (A549) cell lines. Both compounds showed antiproliferative effects correlating with their SIRT2 inhibition potency. They also increased the acetylation level of α-tubulin, indicating that SIRT2 is likely to be the target in cancer cells. A binding mode of the inhibitors that is consistent with the SAR data was proposed based on a homology model of SIRT2.
- Seifert, Tina,Malo, Marcus,Kokkola, Tarja,Engen, Karin,Fridén-Saxin, Maria,Wallén, Erik A. A.,Lahtela-Kakkonen, Maija,Jarho, Elina M.,Luthman, Kristina
-
p. 9870 - 9888
(2015/02/05)
-
- Synthetic strategies for the synthesis and transformation of substituted pyrrolinones as advanced intermediates for rhazinilam analogues
-
The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O-methyl O-trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high-yielding steps into the pyrrolic precursors 7a-c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described.
- Kholod, Inga,Vallat, Olivier,Buciumas, Ana-Maria,Neels, Antonia,Neier, Reinhard
-
supporting information
p. 7865 - 7877
(2015/03/04)
-
- HETEROARYL INHIBITORS OF PDE4
-
The present invention relates to compounds and methods useful as inhibitors of phosphodiesterase 4 (PDE4) for the treatment or prevention of disease.
- -
-
Paragraph 0832
(2014/05/24)
-
- Ugi 4-CR synthesis of γ- And δ-lactams providing new access to diverse enzyme interactions, a PDB analysis
-
A three step synthesis of N-unsubstituted tetrazolo γ- and δ-lactams involving a key Ugi-4CR is presented. The compounds, otherwise difficult to access, are conveniently synthesized in overall good yields by our route. PDB analysis of the N-unsubstituted γ- and δ-lactam fragment reveals a strongly tri-directional hydrogen bond donor acceptor interaction with the amino acids of the binding sites.
- Boltjes, André,Liao, George P.,Zhao, Ting,Herdtweck, Eberhardt,D?mling, Alexander
-
p. 949 - 952
(2014/07/08)
-
- Total syntheses of (+)-sesamin and (+)-sesaminol
-
Total syntheses of (+)-sesamin (1a ) and (+)-sesaminol (1b), which are major components of sesame lignans derived from Sesamum indicum, were accomplished in a highly stereo-controlled manner. Key steps include an L-proline-catalyzed cross-a ldol reaction, which was accelerated with the aid of bifunctional urea 7, and the construction of a furofuran lignan skeleton through a quinomethide intermediate.
- Ishikawa, Ryo,Yoshida, Naoto,Akao, Yusuke,Kawabe, Yusuke,Inai, Makoto,Asakawa, Tomohiro,Hamashima, Yoshitaka,Kan, Toshiyuki
-
supporting information
p. 1572 - 1574
(2015/02/19)
-
- Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes
-
An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities. The Royal Society of Chemistry 2013.
- Altendorfer, Mario,Raja, Aruna,Sasse, Florenz,Irschik, Herbert,Menche, Dirk
-
p. 2116 - 2139
(2013/04/23)
-
- COMPOUND AND METHOD
-
A compound of formula (I): (I) wherein Y is, Z is OR10, NR11R11 SR11, S(0)R11 S02R11, R10 is H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, CO-R11, or a protecting group, and R11 is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, or alkoxyl; a process for making a compound of formula (I); and a process for making a prostaglandin or a prostaglandin analogue using a compound of formula (I).
- -
-
Page/Page column 115
(2014/01/08)
-
- AMIDO-FLUOROPHOSPHITE COMPOUNDS AND CATALYSTS
-
Amido-fluorophosphite compounds and catalyst systems comprising at least one amido-fluorophosphite ligand compound in combination with a transition metal are described. Moreover, the use of amido-fluorophosphite containing catalysts for transition metal catalyzed processes, especially to the hydroformylation of various olefins to produce aldehydes are also described.
- -
-
Page/Page column 27
(2013/03/26)
-
- Compositions, Synthesis, and Methods of Using Cycloalkylmethylamine Derivatives
-
The present invention provides novel cycloalkylmethylamine derivatives, and methods of preparing cycloalkylmethylamine derivatives. The present invention also provides methods of using cycloalkylmethylamine derivatives and compositions of cycloalkylmethylamine derivatives. The pharmaceutical compositions of the compounds of the present invention can be advantageously used for treating and/or preventing obesity and obesity related co-morbid indications and depression and depression related co-morbid indications.
- -
-
Page/Page column 31-32
(2012/07/14)
-
- New tetraphosphorus ligands for highly linear selective hydroformylation of allyl and vinyl derivatives
-
New tetraphosphorus ligands have been developed and applied in the rhodium-catalyzed regioselective hydroformylation of a variety of functionalized allyl and vinyl derivatives. Remarkably high linear selectivity was obtained by these tetraphosphorus ligands. The ligand that bears strong electron-withdrawing 2,4-difluorophenyl groups is the most effective one in affording linear aldehydes. The Rh/tetraphosphorus ligand catalyst is highly effective to produce linear aldehydes from functionalized allyl derivatives with heteroatoms or aromatic groups directly adjacent to the allyl group. For vinyl derivatives, the ligand is highly linear selective for acrylic derivatives, styrene, vinyl pyridine, and vinyl phthalimide. Linear to branch ratios of 26:1 and 10:1 were obtained for the hydroformylation of styrene and allyl cyanide, respectively. New tetraphosphorus ligands have been developed and applied in the rhodium-catalyzed regioselective hydroformylation of a variety of allyl and vinyl olefins (see scheme). Remarkably high linear selectivities were obtained by these ligands. Linear-to-branch ratios of 26:1 and 10:1 were obtained for the hydroformylation of styrene and allyl cyanide, respectively. Copyright
- Cai, Chaoxian,Yu, Shichao,Cao, Bonan,Zhang, Xumu
-
experimental part
p. 9992 - 9998
(2012/09/07)
-
- Generation of α,β-unsaturated platinum carbenes from homopropargylic alcohols: Rearrangements to polysubstituted furans
-
A number of diversely substituted furans are synthesized via a cycloisomerization process that goes through a unique metal carbene species. Both ligand structure and the nature of the leaving group are evaluated. The characteristics of the carbene intermediate can be modulated, resulting in highly selective hydrogen or silicon group migrations.
- Allegretti, Paul A.,Ferreira, Eric M.
-
supporting information; experimental part
p. 5924 - 5927
(2011/12/16)
-
- Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia
-
Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1.
- Tamura, Satoru,Kaneko, Masafumi,Shiomi, Atsushi,Yang, Guang-Ming,Yamaura, Toshiaki,Murakami, Nobutoshi
-
scheme or table
p. 1837 - 1839
(2010/07/02)
-
- NAPHTHYLACETIC ACIDS
-
The invention is concerned with the compounds of formula (I) and pharmaceutically acceptable salts and esters thereof, wherein X, Q, and R1-R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists or partial agonists at the CRTH2 receptor and may be useful in treating diseases and disorders associated with that receptor such as asthma.
- -
-
Page/Page column 67-68
(2010/06/15)
-
- KMnO4-mediated oxidation as a continuous flow process
-
An efficient and easily scalable transformation of alcohols and aldehydes to carboxylic acids and nitroalkane derivatives to the corresponding carbonyls and carboxylic acids using permanganate as the oxidant within a continuous flow reactor is reported. Notably, the generation and downstream processing of MnO2 slurries was not found to cause any blocking of the reactor when ultrasound pulses were applied to the flow system.
- Sedelmeier, Joerg,Ley, Steven V.,Baxendale, Ian R.,Baumann, Marcus
-
supporting information; experimental part
p. 3618 - 3621
(2010/11/17)
-
- Scope and limitations of the Minisci reaction for the synthesis of aza-heterocycles
-
Attempts to prepare several classes of aza-heterocycles by application of the Minisci radical cyclisation reaction are described. Competing β-scission, hydrolytic cleavage and lactonisation reactions were found to be major hurdles to adopting this strategy for the synthesis of such targets.
- Burgin, Ryan N.,Jones, Simon,Tarbit
-
scheme or table
p. 6772 - 6774
(2010/04/27)
-
- Synthesis of γ-amino esters via Mn-mediated radical addition to chiral γ-hydrazonoesters
-
Highly stereoselective Mn-mediated couplings of alkyl iodides with chiral N-acylhydrazones bearing ester functionality afford a series of γ-hydrazino esters, including γ-substituted, α,γ-disubstituted, and α,α,γ-trisubstituted examples. In contrast to prior work with chiral N-acylhydrazones, high stereoselectivity was observed even in the absence of Lewis acid. Microwave-assisted acylation with trifluoroacetic anhydride and reductive N-N bond cleavage provided the γ-amino ester functionality in a synthetically useful N-TFA-protected form.
- Friestad, Gregory K.,Banerjee, Koushik
-
scheme or table
p. 1095 - 1098
(2009/07/25)
-
- Highly regioselective and rapid hydroformylation of alkyl acrylates catalyzed by a rhodium complex with a tetraphosphorus ligand
-
Alkyl acrylates have been hydroformylated to the linear aldehydes with high regioselectivity (linear/branch > 99/1) and extraordinarily high average turnover frequencies (up to 5400 h-1) by using a rhodium complex with a tetraphosphorus ligand.
- Yu, Shichao,Chie, Yu-Ming,Zhang, Xumu
-
experimental part
p. 537 - 540
(2009/11/30)
-
- Gewald synthesis of aminothiophene carboxylic acids providing new dipeptide analogues
-
A new multicomponent synthesis of 2-aminothiophene carbocyclic acids 4 by reaction of methyl 2-siloxycyclopropane-carboxylates 1, alkyl cyanoacetates, and elemental sulfur is reported. This version of the Gewald thiophene synthesis rapidly provides a new type of δ-amino acids, which can be considered as dipeptide analogues. Smooth protective-group manipulations allowed regio-and chemoselective couplings with L-phenylalanine derivatives furnishing new tripeptide analogues such as 5 and 8 or products of type 10. Georg Thieme Verlag Stuttgart.
- ?zbek, Hülya,Veljkovic, Ivana S.,Reissig, Hans-Ulrich
-
scheme or table
p. 3145 - 3148
(2009/06/17)
-
- Novel synthesis of substituted pyrrolidines and piperidines via radical addition-ionic cyclization reaction of oxime ethers
-
We have developed a novel synthetic route to nitrogen-containing heterocycles via radical addition-ionic cyclization reaction. Treatment of oxime ethers carrying the tosyloxy group with Et3B and alkyl iodide in the presence of Lewis acid gave the substituted pyrrolidines and piperidines. The reaction of oxime ethers carrying the methoxycarbonyl group proceeded under the same conditions to give the amino esters, which were easily converted into the corresponding lactams by the treatment with concd HCl. On the other hand, the oxime ether bearing the phenoxycarbonyl group afforded directly alkylated lactams under the radical reaction conditions. The utility of this domino reaction was demonstrated by the synthesis of (±)-bgugaine and the formal synthesis of 5,8-disubstituted indolizidine alkaloids.
- Miyata, Okiko,Takahashi, Shinya,Tamura, Akira,Ueda, Masafumi,Naito, Takeaki
-
p. 1270 - 1284
(2008/09/17)
-
- N,N-acetals as N-acyliminium ion precursors: Synthesis and absolute stereochemistry of epiquinamide
-
(Chemical Equation Presented) A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination of the absolute configuration of the natural product. Key steps in the sequence involved chemoenzymatic formation of an enantiomerically pure cyanohydrin, reductive cyclization to the corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor to enable construction of the second ring.
- Wijdeven, Marloes A.,Wijtmans, Roel,Van Den Berg, Rutger J. F.,Noorduin, Wim,Schoemaker, Hans E.,Sonke, Theo,Van Delft, Floris L.,Blaauw, Richard H.,Fitch, Richard W.,Spande, Thomas F.,Daly, John W.,Rutjes, Floris P. J. T.
-
supporting information; experimental part
p. 4001 - 4003
(2009/05/30)
-
- Synthesis of (+/-)-hamigeran B, (-)-hamigeran B, and (+/-)-1-epi-hamigeran B: use of bulky silyl groups to protect a benzylic carbon-oxygen bond from hydrogenolysis.
-
Enone 42 was converted into diene 56, which was then subjected to hydrogenation. Use of the tert-butyldimethylsiloxy groups enforces facial selectivity and protects the C(5) oxygen from hydrogenolysis. The resulting product (55) is easily converted into hamigeran B (1), a marine natural product with powerful activity against herpes and polio viruses. Optically pure enone 73 was made by use of a Meyers' auxiliary and converted into (-)-hamigeran B with the natural absolute configuration.
- Clive, Derrick L J,Wang, Jian
-
p. 2773 - 2784
(2007/10/03)
-
- 3,5-Disubstituted-[1,2,4]-oxadiazoles and analogs as activators of caspases and inducers of apoptosis and the use thereof
-
Disclosed are 3,5-disubstituted-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar1, R2, A, B and D are defined herein. The present invention relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention may be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.
- -
-
-
- QUINAZOLINE COMPOUNDS
-
Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a sulphur atom and optionally containing one or more nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.
- -
-
-
- Covalent Linking of Coordination-Organized Slipped Cofacial Porphyrin Dimers
-
Coordination-organized porphyrin dimers of 5,15-bis[2-(allyloxycarbonyl)ethyl]- and bis[3-(allyloxy)propyl]-20-(1-methyl-2-imidazolyl)porphyrinatozinc were covalently linked by an intramolecular olefin metathesis reaction in excellent yields (93-98%). It was found that the yields of the intramolecular metathesis reaction depended strongly on the molecular length of the substituent at the 5 and 15 positions. Introducing longer 3-(allyloxycarbonyl)propyl and 4-(allyloxycarbonyl)butyl substituents decreased sharply the yields of the covalent linking reaction to 26% and 16%, respectively. The covalently linked dimers maintained their coordination structures even when dissolved in as polar a solvent as pyridine.
- Ohashi, Atsushi,Satake, Akiharu,Kobuke, Yoshiaki
-
p. 365 - 374
(2007/10/03)
-
- Electrosynthesis of esters of mono- and dioxoalkanoic and alkanedioic acids on the basis of nitro-substituted alkyl carboxylates and cycloalkanones
-
A one-pot electrochemical method for the synthesis of methyl monooxoalkanoates with the carbonyl group in position 4, methyl dioxoalkanoates with the oxo groups in positions 4,7-, 6,9-, 7,10-, and 12,15, and methyl 4-oxoalkanedioates was developed. This method is based on amperostatic electrolysis in an undivided cell of the salts of esters of nitroalkanoic acids and their adducts with CH2=CHX (X = Ac, CO2Me).
- Ogibin,Ilovaiskii,Merkulova,Nikishin
-
p. 728 - 733
(2007/10/03)
-