- Access to Diarylmethanols by Wittig Rearrangement of ortho-, meta-, and para-Benzyloxy- N-Butylbenzamides
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The N-butyl amide group, CONHBu, has been found to be an effective promoter of the [1,2]-Wittig rearrangement of aryl benzyl ethers and thus allow the two-step synthesis of isomerically pure substituted diarylmethanols starting from simple hydroxybenzoic acid derivatives. The method is compatible with a wide range of functional groups including methyl, methoxy, and fluoro, although not with nitro and, unexpectedly, is applicable to meta as well as ortho and para isomeric series.
- Aitken, R. Alan,Harper, Andrew D.,Inwood, Ryan A.,Slawin, Alexandra M. Z.
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supporting information
p. 4692 - 4701
(2022/04/07)
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- 1,3 DI-SUBSTITUTED CYCLOBUTANE OR AZETIDINE DERIVATIVES AS HEMATOPOIETIC PROSTAGLANDIN D SYNTHASE INHIBITORS
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A compound of formula (I), wherein R, R1, R2, R3, Y, Y1, a, X, and Z are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne Muscular Dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
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Page/Page column 227
(2018/04/27)
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- Enantioselective synthesis, stereochemical correction, and biological investigation of the rodgersinine family of 1,4-benzodioxane neolignans
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The enantioselective synthesis and chiroptic analysis of all members of the rodgersinine family of 1,4-benzodioxane neolignans has been achieved. ECD spectra and optical rotation analysis determined that the previously published stereochemistry of trans-rodgersinines A and B was incorrect. The cis-rodgersinines A and B did not follow the model ECD study commonly used to assign the absolute stereochemistry of 1,4-benzodioxane natural products. This finding has implications on the absolute stereochemistry of other natural products of this type. Additionally, the rodgersinines were found to have anti-HCV activities.
- Pilkington, Lisa I.,Barker, David,Wagoner, Jessica,Polyak, Stephen J.
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supporting information
p. 1046 - 1049
(2015/03/30)
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- A study towards the regioselective synthesis of the e,e,e trisadduct of C60 via the [4+2] Diels-Alder reaction with tethers bearing orthoquinodimethane precursors
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The regioselective synthesis of an e,e,e trisadduct of C60 via the Diels-Alder reaction with orthoquinodimethanes has been attempted employing the tether-directed remote functionalization approach. Opened-structure tether 10 and macrocyclic tethers 16 and 21 were synthesized for this purpose. The functionalization of C60 afforded inseparable mixtures of regiomeric trisadducts and the regioselective formation of the e,e,e trisadduct was not feasible even when the more preorganized tethers 16 and 21 were employed. The in situ thermal generation of orthoquinodimethanes from the 1,2-bis(bromomethyl)benzene precursors requires high temperatures and is followed by fast, irreversible cycloaddition with C60 to afford thermally stable products, which prevents the achievement of high regioselectivities.
- Ioannou, Charalambos P.,Chronakis, Nikos
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- Choline chloride based deep eutectic solvent as an efficient solvent for the benzylation of phenols
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Deep eutectic solvents (such as the combination of urea and choline chloride) are found to be promising solvent and phase-transfer-media for benzylation of phenol. These methods avoided the complexity of multiple alkylations giving selectively O-alkylated aromatic products. Good to excellent yields of the corresponding benzyl phenyl ether were obtained. The non-toxic, biodegradable, inexpensive, and recyclable nature of DES make this protocol green and cost-effective.
- Singh, Abhilash S.,Shendage, Suresh S.,Nagarkar, Jayashree M.
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p. 7243 - 7246
(2015/02/02)
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- Synthesis of 1,7-dimethoxy-2-hydroxyxanthone, a natural product with potential activity on erectile dysfunction
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The natural product, 1,7-dimethoxy-2-hydroxyxanthone (1), isolated from Securidaca inappendiculate Hassk, has a potential in the treatment of erectile dysfunction due to its significant relaxation activity on rabbit Corpus cavernosum. However, the isolation of compound 1 is problematic because of its high similarity in structure to its analogs. In this paper, the first synthesis of 1 was reported featuring two key reactions: a copper-catalyzed coupling reaction and an intramolecular cyclization.
- Liu, Wen-Jing,Mei, De-Sheng,Duan, Wen-Hu
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p. 515 - 517
(2013/07/27)
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- [Pd(L)Cl2]-catalyzed selective hydroxylation of arylboronic acids to phenols
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The palladium complex [Pd(L)Cl2] (1) has been prepared by the reaction of Pd(COD)Cl2 (COD = 1,5-cyclooctadiene) with L [N,N′-bis(diphenylphosphanyl)-2-(diphenylphosphanyl)ethanamine]. The ligand L and complex 1 have been characterized by elemental analysis, mass spectrometry and 1H/31P NMR spectroscopy. In the presence of O2, 1 selectively catalyzes the hydroxylation of a variety of arylboronic acids to the corresponding phenol derivatives in solvents with low-dielectric constants at 298 K, although in solvents with high dielectric constants the same reaction leads to the formation of both phenol and the coupled product, i.e. biaryl. The mechanistic aspects of the selective phenol formation from arylboronic acid with 1 have been addressed.
- Chowdhury, Abhishek Dutta,Mobin, Shaikh M.,Mukherjee, Soumen,Bhaduri, Sumit,Lahiri, Goutam Kumar
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experimental part
p. 3232 - 3239
(2011/08/07)
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- Syntheses and characterization of nimesulide derivatives for dual enzyme inhibitors of both cyclooxygenase-1/2 and 5-lipoxygenase
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Cyclooxygenase-1/2 (COX-1/2) and 5-lipoxygenase (5-LOX) are enzymes in two different pathways in the inflammatory process. In the present study, a variety of new nimesulide derivatives were synthesized through incorporation of a 5-LOX pharmacophore into nimesulide followed with some structural modifications, which were then characterized for dual enzyme inhibitors for these two types of enzymes. Their structure-activity relationships (SARs) were studied, and compound 20f was found to be an excellent dual enzyme inhibitor. Its binding conformation and interaction mode were studied with molecular docking experiments. Compound 20f could become a lead compound for further development for potential anti-inflammatory drugs.
- Li, Yue,Chen, Shu-Han,Ou, Tian-Miao,Tan, Jia-Heng,Li, Ding,Gu, Lian-Quan,Huang, Zhi-Shu
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scheme or table
p. 2074 - 2083
(2011/05/05)
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- COMPOUNDS WITH 7-MEMBER CYCLE AND THE PHARMACEUTICAL USE THEREOF FOR PREVENTING AND TREATING DIABETES AND METABOLISM SYNDROME
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The invention discloses a new use of a class of heptacyclic compounds in the preparation of formulations for the prevention and treatment of diabetes and metabolic syndromes; the present invention also discloses a new class of heptacyclic compounds; the present invention also discloses a process for preparing the heptacyclic compounds and a composition containing the same. The heptacyclic compounds of the present invention can be used to effectively preventing or treating diseases such as diabetes and metabolic syndromes.
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Page/Page column 31
(2010/07/06)
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- Synthesis of ranolazine metabolites and their anti-myocardial ischemia activities
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The anti-anginal drug Ranolazine, a partial fatty acid oxidation (pFOX) inhibitor, is thought to modulate the metabolism during myocardial ischemia by activating pyruvate dehydrogenase activity to promote glucose oxidation. Ranolazine and its five principal metabolites: CVT-2512, CVT-2513, CVT-2514, CVT-2738 and CVT-4786, were synthesized. The effect of Ranolazine and its metabolites on the ECG (electrocardiogram) of mice with myocardial ischemia induced by isoprenaline and their effect on alleviating the symptom of myocardial ischemia were tested and compared. The results showed that CVT-2738 and CVT-2513 could be protective against mice myocardial ischemia induced by isoprenaline. Within all the metabolites tested in this study, CVT-2738 exhibited the best potency, however, it was still less potent than Ranolazine.
- Yao, Zhangyu,Gong, Shubo,Guan, Teng,Li, Yunman,Wu, Xiaoming,Sun, Hongbin
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experimental part
p. 1218 - 1222
(2010/06/16)
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- Distinct columnar and lamellar liquid crystalline phases formed by new bolaamphiphiles with linear and branched lateral hydrocarbon chains
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A universal building block for the convergent synthesis of a wide variety of different T-shaped ternary amphiphiles was developed and used for the synthesis of a series of new liquid-crystalline materials composed of a rigid biphenyl core with polar glycerol groups at both ends and linear or branched alkyl chains in a lateral position. In addition, compounds with bulky achiral (2,4,6-trimethylphenoxy, adamantane-1-carboxylate, benzoate) or chiral (menthyl or cholesteryl) substituents attached to the end of the lateral alkyl chain were also investigated. In all cases the lateral chains were connected to the aromatic core by an ether linkage. The effect of the ether linking unit on mesophase stability and mesophase type is discussed with respect to conformational effects. The liquid-crystalline phases were investigated by polarizing microscopy, calorimetry, and X-ray diffraction of surface aligned samples. Upon enlarging the lateral chains a series of different polygonal cylinder phases was observed, which were replaced by lamellar phases and a non-cylinder hexagonal columnar phase by further increasing the size of these substituents. Remarkably, only pentagonal, hexagonal, and giant hexagonal cylinder phases could be observed, whereas mesophases composed of cylinders with a smaller number of sides are missing. No distinct chirality effects were observed for the menthyl- and cholesteryl-substituted compounds. However, the rodlike shape of the polycyclic cholesteryl core leads to a unique phase structure combining an organization of the alicyclic cholesteryl cores perpendicular to the layer planes and the aromatic biphenyl cores parallel to the layer planes.
- Prehm, Marko,Enders, Claudia,Anzahaee, Maryam Yahyaee,Glettner, Benjamin,Baumeister, Ute,Tschierske, Carsten
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supporting information; experimental part
p. 6352 - 6368
(2009/06/25)
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- A facile synthesis of aryl spirodioxines based on a 3H,3′H-2, 2′-spiro-bi(benzo[b][1,4]dioxine) skeleton
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The synthesis of a series of 6,6-bisbenzannulated spiroketals containing a 3H,3′H-2,2′-spirobi(benzo[b][1,4]dioxine) ring system is reported. The key step involves addition of a monobenzyl-protected catechol to the epoxide unit of a glycidol bearing a benzyl-protected catechol. The resultant alcohol adduct is oxidized to a ketone that then undergoes hydrogenation and acid-catalyzed cyclization to produce the desired spirodioxines. Georg Thieme Verlag Stuttgart.
- Brimble, Margaret A.,Liu, Yen-Cheng,Trzoss, Michael
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p. 1392 - 1402
(2008/02/12)
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- Carbohydrate rod conjugates: Ternary rod-coil molecules forming complex liquid crystal structures
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T-shaped polyphilic triblock molecules, consisting of a rodlike p-terphenyl unit, a hydrophilic and flexible laterally attached oligo(oxyethylene) chain terminated by an 1-acylamino-1-deoxy-D-sorbitol unit, and two end-attached lipophilic alkyl chains, have been synthesized by palladium-catalyzed cross-coupling reactions as the key steps. The thermotropic liquid crystalline behavior of these compounds was investigated by polarized light microscopy, differential scanning calorimetry (DSC), and X-ray scattering. We investigated the mode of self-organization as a function of the length and position of the lateral polar chain and the length of the terminal alkyl chains. Depending on the size of the polar and lipophilic segments, a series of unusual liquid crystalline phases was detected. In three of these phases, the space is divided into three distinct periodic subspaces. In addition to a hexagonal channeled layer phase (ChLhex) consisting of layers that are penetrated by polar columns, there are also two honeycomb-like network structures formed by square (Colsqu/p4mm) or pentagonal cylinders (Colsqu/p4gm) . The cylinder walls consist of the terphenyl units fused by columns of alkyl chains, and the interior contains the polar side chains. In addition, a hexagonal columnar phase was observed in which the polar columns are organized in a continuum of terphenyls and alkyl chains with an organization of the terphenyl cores tangentially around the columns with the long axis perpendicular to the columns. For one compound, a reversal of birefringence was observed, which is explained by a reorientation of the terphenyl cores. The addition of protic solvents induces lamellar phases.
- Chen, Bin,Baumeister, Ute,Pelzl, Gerhard,Das, Malay Kumar,Zeng, Xiangbing,Ungar, Goran,Tschierske, Garsten
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p. 16578 - 16591
(2007/10/03)
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- Simple, efficient, and selective deprotection of phenolic methoxymethyl ethers using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst
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A simple and efficient method has been developed for chemoselective deprotection of phenolic methoxymethyl (MOM) ethers using silica-supported sodium hydrogen sulfate as a heterogeneous catalyst. The conversions occur at room temperature, and the yields of the deprotected phenols are excellent. The method is suitable for deprotection of phenolic MOM ethers of multifunctional bioactive natural products.
- Ramesh,Ravindranath,Das, Biswanath
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p. 7101 - 7103
(2007/10/03)
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- Development of a novel hapten for radioimmunoassay of the lignan, enterolactone in plasma (Serum). Total synthesis of (±)-trans-5- carboxymethoxyenterolactone and several analogues
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A recently developed method for the analysis of the mammalian lignan, enterolactone 1, is based on time-resolved fluoroimmunoassay (TR-FIA) using an europium chelate as a label. This RIA utilizes enterolactone derivatives carrying a carboxylic acid appendage for the production of antiserum and tracer. The synthesis of 5-carboxymethoxyenterolactone 6 and analogues 5, 7 and 8 is described, and their suitability for the method are discussed. (C) 2000 Elsevier Science Ltd.
- M?kel?, Taru,Matikainen, Jorma,W?h?l?, Kristiina,Hase, Tapio
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p. 1873 - 1882
(2007/10/03)
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- Process for the stereoselective preparation of a hetero-bicyclic alcohol enantiomer
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The invention relates to a method for the stereoselective preparation of a hetero-bicyclic alcohol enantiomer, characterized in that a substantially pure enantiomer of the general formula STR1 is prepared from a compound of the general formula STR2 wherein the variable are as defined as in claim 1. The method comprises the following successive reaction steps: (i) reaction with a substantially enantiomerically pure compound of the general formula STR3 wherein Z, R3 and R4 are defined as in claim 1; (ii) subjection of the compound formed to a deprotection/ring-closure reaction; (iii) optionally deprotection of the hydroxy group of the ring-closed product. The invention further relates to enantiomerically pure intermediates, the preparation of these intermediates and the preparation of a starting compound.
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-
- Synthesis of the 2-deoxyisomaltose analogue of acarbose by an improved route to chiral valieneamines
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A 2-deoxyisomaltose analogue of acarbose was stereoselectively synthesised in 11 steps with a total yield of 7% starting from 2,6-dibromo-2,6-dideoxy-D-mannono-1,4-lactone (6). The latter was reduced to the lactol, converted to the methyl glycoside (7) and hydrogenated to the 6-bromo-2,6-dideoxyglycoside (8). Benzylation of the hydroxy groups, elimination of bromine to a 5-ene and Ferrier carbocyclisation gave (2S,3R)-2,3-bisbenzyloxycyclohex-5-enone (12). 1,2-addition of benzyloxymethyl lithium at -110 C gave a 6:1 mixture of tertiary alcohols 13; the (1S) isomer was the major one. Reaction with trichloroacetyl isocyanate gave a carbamate 19, which, when dehydrated to the cyanate, spontaneously underwent [1,3] sigmatropic rearrangement to an isocyanate, which on addition of methanol gave the methylcarbamate 20. Basic hydrolysis of this compound gave (2R,3R,5R)-5-amino-1-benzyloxy-methyl-2,3-bis(benzyloxy)cyclohex-6-ene (22), which could be deprotected to 2-deoxyvalieneamine (5). Reaction with 2-azidoethyl 2,3,4-tri-O-benzyl-6-O-triflyl-α-D-glucopyranoside (34) gave the secondary amine 35, which was completely de-O-protected with sodium in ammonia to give 6-deoxy-6-((1R,3R,4R)-3,4-dihydroxy-5-hydroxymethylcyclohex-5-enylamino)-D- glucose (4), the 2-deoxyisomaltose analogue of acarbose.
- Tagmose, Tina M.,Bols, Mikael
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p. 453 - 462
(2007/10/03)
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- The Baeyer-Villiger Oxidation of Aromatic Aldehydes and Ketones with Hydrogen Peroxide Catalyzed by Selenium Compounds
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A series of organoselenium compounds was investigated as activators of hydrogen peroxide in the Baeyer-Villiger oxidation.As a result, a convenient and cheap method for transformation of aromatic aldehydes, having polycondensed ring systems or electron-donating substituents, and polymethoxy derivatives of acetophenone, into phenols was elaborated.This method utilizes hydrogen peroxide activated by areneseleninic acids, as oxidizing agent.
- Syper, Ludwik
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p. 167 - 172
(2007/10/02)
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- The Complexation of the Diquat Dication by Dibenzo-3n-crown-n Ethers
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Spectrophotometric investigations of equimolar mixtures of diquat bis(hexafluorophosphate) (2) and a range of dibenzo-3n-crown-n ethers in acetonitrile reveal the existence of charge-transfer absorption bands at ca. λmax 400 nm.These absorptions are attributable to intermolecular ?-? charge transfer between the electron-rich catechol units of the dibenzo-crown ethers and the electron-deficient bipyridinium ring system of the diquat dication.The qualitative conclusion from these experiments, that the most stable 1:1 complex is formed between dibenzo-30-crown-10 (14) and diquat bis(hexafluorophosphate) (2), led to the isolation from dichloromethane methanol-n-heptane of red crystals of 2 suitable for X-ray crystallography.Although the crystal structure analysis revealed that there are two independent sets of 1:1 complexes (I and II) in the unit cell, the gross structural features of the two complexes are very similar.In addition to the paralell alignment of their three aromatic rings to accommodate the stabilising intermolecular ?-? charge-transfer interaction, there is probably some further host-guest stabilisation to be gained on account of favourable electrostatic interactions between the phenolic oxygen atoms in the host and the nitrogen atoms in the pyridinium rings of the guest.Moreover, there is some evidence for weak C-H...O hydrogen bonding involving principally H-6 and H-6' on the bipyridinium ring system of the guest and certain -CH2OCH2- oxygen atoms in the host.As evidenced by 1H n.m.r. spectroscopy in CD3COCD3, these non-covalent bonding interactions are probably responsible for the formation of stable and ordered 1:1 complexes with similar gross structural features in solution, at least in the cases where dibenzo-30-crown-10 (14), dibenzo-33-crown-11 (15), and dibenzo-36-crown-12 (16) are the hosts.Further evidence for the 1:1 stoicheiometry of these solution complexes, as well as for the complex involving dibenzo-27-crown-9 (13), has come from equilibrium constant measurements for the association between the dibenzo-3n-crown-n (n = 9-12) hosts (13)-(16) and diquat bis(hexafluorophosphate) (2) in acetone.A quantitative treatment of the charge-transfer absorption bands at 400 nm, which affords Ka values of 410, 17500, 10800, and 2000 M-1 for n = 9, 10, 11, and 12, respectively, provides convincing quantitative evidence for (a) 1:1 stoicheiometry and (b) the relative stabilities of the 1:1 complexes in solution.In the case of dibenzo-24-crown-8 (11), a complex of 2:1 (guest-host) stoicheiometry is believed to be formed in acetone with a Ka value of 385000 M-2, as shown by a successfull quantitative treatment of the charge-transfer absorption data by an independent method.
- Colquhoun, Howard M.,Goodings, Eric P.,Maud, John M.,Stoddart, J. Fraser,Wolstenholme, John B.,Williams, David J.
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p. 607 - 624
(2007/10/02)
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- Opening of Cyclic Acetals by Trichloro-, Dichloro- and Tribromo-borane
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The rate-determining step in the ring opening of cyclic acetals by trichloroborane to yield α-chloro-ethers is shown to be consistent with the formation of an oxocarbenium ion.Subsequent reduction provides a general route for the conversion of a diol into a hydroxy-ether.Tribromoborane is a more powerful and dichloroborane a less powerful reagent than trichloroborane.
- Bonner, Trevor G.,Lewis, David,Rutter, Keith
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p. 1807 - 1810
(2007/10/02)
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- (S)-1-[2-(4-HYDROXY-S-(1-ALKYLAMINO-PROPOXY)PHENYLALKYL]-4-PHENYLPIPERAZINES
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There are disclosed compounds of the formula STR1 wherein R 1 is selected from the group consisting of lower alkyl; R 8 is selected from the group consisting of--O--(CH 2) n--wherein n is 2 to 20, STR2 and R 6 is selected from the group consisting of hydrogen or lower alkoxy, and STR3 wherein R 1 is selected from the group consisting of lower alkyl; R 8 is selected from the group consisting of--O--(CH 2) n--wherein n is 2 to 20, STR4 and R 6 is selected from the group consisting of hydrogen or lower alkoxy and racemates thereof.There are also disclosed processes and intermediates utilized to produce the end products. The end products have utility as agents exhibiting both α and selective β adrenergic blocking action.
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- Absolute configuration of glycerol derivatives. 4. Synthesis and pharmacological activity of chiral 2 alkylaminomethylbenzodioxans, competitive α adrenergic antagonists
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The optical isomers of α-adrenergic receptor antagonists prosympal (2), piperoxan (3), and dibozane (4) were prepared by methods establishing the absolute configuration of each. (2S)-3-(2'-Hydroxyphenoxy)-1,2-propanediol ditosylate (10) was prepared from (2R)-3-tosyloxy-1,2-propanediol acetonide (6). Intramolecular displacement afforded (2S)-tosyloxymethylbenzodioxan [(2R)-11]. Reaction of (2R)-11 with the appropriate amine (diethylamine, piperidine, or piperazine) afforded the 2S isomers of 2, 3, and 12, respectively. Reaction of (2S)-12 with (2R)-11 afforded the SS isomer of 4. Reaction of (2S)-3-benzoloxy-1,2-propanediol ditosylate (14) with catechol (NaOMe) afforded (2R)-benzyloxymethylbenzodioxan (15). Subjecting 15 to hydrogenolysis, tosylation, and displacement with the appropriate amine afforded 2R isomers of 2, 3, and 12. Reaction of (2R)-12 with (2S)-11 afforded (RR)-4. Reaction of (2R)-12 with (2R)-11 afforded meso-4. The S isomers were more effective antagonists to the α-adrenergic response of methoxamine-induced contraction of rabbit aortic strips by twofold in 2 and 18-19-fold in 3 and 4. meso-4 was as effective as the SS isomer of 4. The results are interpreted in terms of a similar conformational distribution of aminoalkyl, oxygen, and aromatic functional groups of the (S)-benzodioxans and (R)-epinephrine.
- Nelson,Wennerstrom,Dyer,Engel
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p. 880 - 885
(2007/10/04)
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