- A Novel Glyceryl Ester (Glyceryl Dendryphiellate A), a Trinor-eremophilane (Dendryphiellin A1), and Eremophilanes (Dendryphiellin E1 and E2) from the Marine Deuteromycete Dendryphiella salina (SUTHERLAND) PUGH et NICOT
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Continuing studies of the global extracts from cultures of the marine deuteromycete Dendryphiella salina have led to the isolation of novel compounds that add to the scarce list of marine fungal metabolites.Besides (22E)-ergosta-4,6,8(14),22-tetraen-3-one
- Guerriero, Antonio,Cuomo, Vincenzo,Vanzanella, Fortunato,Pietra, Francesco
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Read Online
- Gold(I)-catalyzed, one-pot, oxidative formation of 2,4-disubstituted thiazoles: Application to the synthesis of a pateamine-related macrodiolide
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Thiazoles are important heterocyclic motifs in many target molecules. Extension of a reported gold(I)-catalyzed oxidative coupling of alkynes and thioamides to the synthesis of functionalized thiazole-containing products is presented, including the compatibility of this reaction with ester, protected hydroxyl, alkene and thioether groups. The utility of this one-pot process is demonstrated in the preparation of the thiazole-containing macrodiolide of a simplified analogue of pateamine A.
- Xu, Tao,Cuyamendous, Claire,Brown, Sarah L.,Andreassend, Sarah K.,Cumming, Hemi,Evans, Gary B.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
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- A Novel Agonist of the Type 1 Lysophosphatidic Acid Receptor (LPA1), UCM-05194, Shows Efficacy in Neuropathic Pain Amelioration
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Neuropathic pain (NP) is a complex chronic pain state with a prevalence of almost 10% in the general population. Pharmacological options for NP are limited and weakly effective, so there is a need to develop more efficacious NP attenuating drugs. Activation of the type 1 lysophosphatidic acid (LPA1) receptor is a crucial factor in the initiation of NP. Hence, it is conceivable that a functional antagonism strategy could lead to NP mitigation. Here we describe a new series of LPA1 agonists among which derivative (S)-17 (UCM-05194) stands out as the most potent and selective LPA1 receptor agonist described so far (Emax = 118%, EC50 = 0.24 μM, KD = 19.6 nM; inactive at autotaxin and LPA2-6 receptors). This compound induces characteristic LPA1-mediated cellular effects and prompts the internalization of the receptor leading to its functional inactivation in primary sensory neurons and to an efficacious attenuation of the pain perception in an in vivo model of NP.
- González-Gil, Inés,Zian, Debora,Vázquez-Villa, Henar,Hernández-Torres, Gloria,Martínez, R. Fernando,Khiar-Fernández, Nora,Rivera, Richard,Kihara, Yasuyuki,Devesa, Isabel,Mathivanan, Sakthikumar,Del Valle, Cristina Rosell,Zambrana-Infantes, Emma,Puigdomenech, María,Cincilla, Giovanni,Sanchez-Martinez, Melchor,Rodríguez De Fonseca, Fernando,Ferrer-Montiel, Antonio V.,Chun, Jerold,López-Vales, Rubén,López-Rodríguez, María L.,Ortega-Gutiérrez, Silvia
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supporting information
p. 2372 - 2390
(2020/01/02)
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- Synthesis and antimicrobial screening of novel 1,3-dioxolanes linked to N-5 of 5H-1,2,4-triazino[5,6-b]indole-3-thiol
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Synthesis of 1-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]-1H-indole-2,3-dione (10) was achieved by coupling 1H-indole-2,3-dione (16) with (R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate (15) in the presence of sodium hydride in dry N,N-dimethylformamide at room temperature in a closed Erlenmeyer flask. Condensation of 10 with hydrazinecarbothioamide in water afforded the thiosemicarbazone derivative 17; its subsequent cyclization with potassium carbonate in water gave the corresponding thione 18 in good yield. The 3-allylthio and 3-benzylthio derivatives 20 and 21 were also prepared by alkylating thiol 19 with alkyl halides in aqueous sodium hydroxide or coupling of 3-(allylthio/benzylthio)-5H-1,2,4-triazino[5,6-b]indoles (23 and 24) with compound 15 in NaH/DMF. Compound 20 was isomerized to a mixture of geometrical isomers (E/Z)-5-[(2,2-dimethyl-1,3-dioxolan-4-yl)-methyl]-3-(prop-1-en-1-ylthio)-5H-1,2,4-triazino[5,6-b]indoles (25 and 26), evidenced by their 1H- and 13C-NMR spectra taken in deuterodimethyl sulfoxide. Structural elucidation of the synthesized compounds was realized using FT-IR, 1H-NMR, 13C-NMR, mass spectrometry and elemental analysis. The newly synthesized compounds were found to possess moderate inhibitory activity against the fungus Candida albicans compared to clotrimazole as reference control. Compounds 10, 17, 19, 20, 21, 23 and 24 had mean growth inhibition zones (IZ) and minimal inhibitory concentrations (MIC) in the range of 12–15 mm and 31.25–200 μg mL-1, respectively, with inhibition levels in the range 70.58–88.23 %. Compound 19 exhibited moderate activity against Gram-positive bacteria Staphylococcus aureus relative to imipenem as the standard drug. All compounds were inactive against Escherichia coli and Pseudomonas aeruginosa.
- Ramadan, El Sayed,Rasheed, Hanaa A.,El Ashry, El Sayed H.
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- Compound containing ferrocene base element and preparation method and application of compound
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The invention discloses a compound containing a ferrocene base element and a preparation method and application of the compound. A structure formula of the compound containing the ferrocene base element is shown in a formula I. The formula I is shown in the description.
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Paragraph 0062-0067
(2019/02/10)
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- COMPOUNDS AND COMPOSITIONS FOR RADIATION THERAPY AND METHODS OF USING THE SAME
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The present disclosure relates to bisphenol ether derivatives and compositions thereof, which can be useful in radiation therapy for treatment of diseases, such as prostate cancer. In particular, the compounds of the present disclosure containing a radiolabeled atom can be useful in targeted delivery of radionuclides for treatment of lesions, tumors, and/or cancer cells.
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Paragraph 293
(2018/01/15)
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- BISPHENOL DERIVATIVES AND THEIR USE AS ANDROGEN RECEPTOR ACTIVITY MODULATORS
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Compounds having a structure of Formula I: or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R11a, R11b, R11c, R11d, and X, are as defined herein, are provided. Uses of such compounds for modulating androgen receptor activity, imaging diagnostics in cancer and therapeutics, and methods for treatment of subjects in need thereof, including prostate cancer are also provided.
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Paragraph 0271
(2017/11/07)
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- Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic
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Itraconazole (ITZ) is an FDA-approved member of the triazole class of antifungal agents. Two recent drug repurposing screens identified ITZ as a promising anticancer chemotherapeutic that inhibits both the angiogenesis and hedgehog (Hh) signaling pathways. We have synthesized and evaluated first- and second-generation ITZ analogues for their anti-Hh and antiangiogenic activities to probe more fully the structural requirements for these anticancer properties. Our overall results suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two distinct cellular mechanisms of action govern the anticancer properties of the ITZ scaffold.
- Pace, Jennifer R.,Deberardinis, Albert M.,Sail, Vibhavari,Tacheva-Grigorova, Silvia K.,Chan, Kelly A.,Tran, Raymond,Raccuia, Daniel S.,Wechsler-Reya, Robert J.,Hadden, M. Kyle
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supporting information
p. 3635 - 3649
(2016/05/24)
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- PROCESS FOR PREPARATION OF PROSTAGLANDIN F2 ALPHA ANALOGUES
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A convergent synthesis of the prostaglandin F2α analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ω-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate.
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Paragraph 0221; 0222
(2015/02/19)
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- HALOGENATED COMPOUNDS FOR CANCER IMAGING AND TREATMENT AND METHODS FOR THEIR USE
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Compounds having a structure of Formula I: (Formula (I)) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R 3, R4, R5, X1, X2, X3 and X4 are as defined herein, and wherein the compound comprises at least one F, CI, Br, I or 123I moiety, are provided. Uses of such compounds for imaging diagnostics in cancer and therapeutics methods for treatment of subjects in need thereof, including prostate cancer as well as methods and intermediates for preparing such compounds are also provided.
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Page/Page column 52-53
(2015/03/28)
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- A Clickable and Photocleavable Lipid Analogue for Cell Membrane Delivery and Release
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For drug delivery purposes, the ability to conveniently attach a targeting moiety that will deliver drugs to cells and then enable controlled release of the active molecule after localization is desirable. Toward this end, we designed and synthesized clickable and photocleavable lipid analogue 1 to maximize the efficiency of bioconjugation and triggered release. This compound contains a dibenzocyclooctyne group for bioorthogonal derivatization linked via a photocleavable 2-nitrobenzyl moiety at the headgroup of a synthetic lipid backbone for targeting to cell membranes. To assess delivery and release using this system, we report fluorescence-based assays for liposomal modification and photocleavage in solution as well as through surface immobilization to demonstrate successful liposome functionalization and photoinduced release. In addition, fluorophore delivery to and release from live cells was confirmed and characterized using fluorescence microscopy and flow cytometry analysis in which 1 was delivered to cells, derivatized, and photocleaved. Finally, drug delivery studies were performed using an azide-tagged analogue of camptothecin, a potent anticancer drug that is challenging to deliver due to poor solubility. In this case, the ester attachment of the azide tag acted as a caging group for release by intracellular esterases rather than through photocleavage. This resulted in a dose-dependent response in the presence of liposomes containing delivery agent 1, confirming the ability of this compound to stimulate delivery to the cytoplasm of cells.
- Alam, Shahrina,Alves, Daiane S.,Whitehead, Stuart A.,Bayer, Andrew M.,McNitt, Christopher D.,Popik, Vladimir V.,Barrera, Francisco N.,Best, Michael D.
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p. 1021 - 1031
(2015/06/30)
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- A novel convergent synthesis of the potent antiglaucoma agent travoprost
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The 16-(3-trifluoromethyl)phenoxy PGF2α analogue travoprost (8a) has potent topical ocular activity. A novel convergent synthesis of 13,14-en-15-ol PGF2α analogues was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone (5Z)-(+)-15 with a new enantiomerically pure aldehyde ω-chain synthon (S)-(-)-16a. Subsequent hydrolysis of protecting groups and final esterification of fluprostenol (7a) yielded travoprost (8a). The main advantages are the preparation of high purity travoprost (8a) and the application of comparatively cheap reagents. The novel convergent strategy allows the synthesis of a whole series of 13,14-en-15-ol PGF2α analogues from a common and structurally advanced prostaglandin intermediate 15. The preparation and identification of two synthetic impurities, 15-epi isomer (8b) of travoprost and a new prostaglandin related ester (5Z)-(+)-18, are also described.
- Dams, Iwona,Chodyński, Micha?,Krupa, Ma?gorzata,Pietraszek, Anita,Zezula, Marta,Cmoch, Piotr,Kosińska, Monika,Kutner, Andrzej
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p. 1634 - 1648
(2013/02/26)
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- PROCESS FOR PREPARATION OF PROSTAGLANDIN F2α ANALOGUES
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A convergent synthesis of the prostaglandin F2α analogues, travoprost and bimatoprost, was developed employing Julia-Lythgoe olefination of the structurally advanced phenylsulfone with an enantiomerically pure aldehyde ω-chain synthon. The novel convergent strategy allows the synthesis of a whole series of prostaglandin analogues of high purity from a common and structurally advanced prostaglandin intermediate.
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Page/Page column 33; 34
(2013/09/26)
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- Synthesis of phosphonoglycine backbone units for the development of phosphono peptide nucleic acids
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A series of phosphono-modified backbone mimics based on achiral and chiral N-(dihydroxypropyl)glycine units were obtained by sequential addition of phosphonate and nucleobase moieties to suitably protected dihydroxypropylamines. Simple synthetic strategies enabled the preparation of various target derivatives that will be useful as building blocks for the preparation of new synthetic polymers containing a phosphonate internucleotide linkage in place of the standard phosphodiester bond. Copyright
- Doboszewski, Bogdan,Groaz, Elisabetta,Herdewijn, Piet
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p. 4804 - 4815
(2013/08/23)
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- Asymmetric synthesis and effect of absolute stereochemistry of YCZ-2013, a brassinosteroid biosynthesis inhibitor
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The four stereoisomers of 2RS,4RS-1-[[2-(2,4-dichlorophenyl)-4-(2-(2- propenyloxy)phenoxymethyl)-1,3-dioxolan-2-yl]methyl]-1H-1,2,4-triazole (YCZ-2013), a novel brassinosteroid biosynthesis inhibitor, were prepared. The diastereomers of 2RS,4R-5 and 2RS,4S-5 were prepared by using the corresponding optically pure R and S toluene-4-sulfonic acid 2,3-dihydroxypropyl ester (R-4,S-4). The enatiomerically and diastereomerically pure acetonide (5) was obtained by a method involving diastereoselective crystallisation of the tosylate salt, followed by re-equilibration with the mother liquor and chromatography. The optical purity of four target compounds (YCZ-2013) was confirmed by chiral high-performance liquid chromatography (HPLC) and NMR. The effects of these stereoisomers on Arabidopsis stem elongation indicated that the cis isomers of 2S,4R-YCZ-2013 and 2R,4S-YCZ-2013 exhibited potent inhibitory activity with IC50 values of approximately 24 ± 3 and 24 ± 2 nM, respectively. The IC50 values of the trans isomers of 2S,4S-YCZ-2013 and 2R,4R-YCZ-2013 are approximately 1510 ± 50 and 3900 ± 332 nM, respectively. Co-application of brassinolide (10 nM), the most potent BR, and GA3 (1 μM) to Arabidopsis seedlings grown in the dark with 2R,4S-YCZ-2013 and 2S,4R-YCZ-2013 revealed that brassinolide recovered the induced dwarfism of Arabidopsis seedlings, whereas GA3 showed no effect.
- Oh, Keimei,Yamada, Kazuhiro,Yoshizawa, Yuko
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p. 6915 - 6919
(2014/01/06)
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- Transporting excess electrons along potential energy gradients provided by 2 ' -deoxyuridine derivatives in dna
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LUMO-level dependent: Chemically modified DNA molecules containing 2'-deoxyuridine (dU) derivatives with various LUMO energy levels have been synthesized to manipulate electron-transfer efficiencies. By arranging thymidine, the dU derivatives, and 5-fluor
- Ito, Takeo,Hamaguchi, Yuta,Tanabe, Kazuhito,Yamada, Hisatsugu,Nishimoto, Sei-Ichi
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supporting information; experimental part
p. 7558 - 7561
(2012/10/18)
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- Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides
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The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure-activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species-specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R)-Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity.
- Wu, Wenyan,Li, Rongti,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Kimbrell, Matthew R.,Amolins, Michael W.,Ukani, Rehman,Datta, Apurba,David, Sunil A.
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experimental part
p. 3198 - 3213
(2010/10/02)
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- Synthesis of hybrid 1,2,3-triazolo-δ-lactams/lactones using Huisgen [3+2] cycloaddition 'click-chemistry' in water
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The synthesis of a new class of hybrid 1,2,3-triazozlo-δ-lactams/lactones has been achieved using the Huisgen [3+2] dipolar cycloaddition 'click-chemistry' reaction of various organic azides with an activated alkyne in water, followed by cyclization.
- Kumar, Indresh,Rana, Sravendra,Cho, Jae Whan,Rode, Chandrashekhar V.
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scheme or table
p. 352 - 355
(2010/06/16)
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- Mycolic Acids Constitute a Scaffold for Mycobacterial Lipid Antigens Stimulating CD1-Restricted T Cells
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CD1-restricted lipid-specific T lymphocytes are primed during infection with Mycobacterium tuberculosis, the causative agent of tuberculosis. Here we describe the antigenicity of glycerol monomycolate (GroMM), which stimulates CD1b-restricted CD4+/s
- Layre, Emilie,Collmann, Anthony,Bastian, Max,Mariotti, Sabrina,Czaplicki, Jerzy,Prandi, Jacques,Mori, Lucia,Stenger, Steffen,De Libero, Gennaro,Puzo, Germain,Gilleron, Martine
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experimental part
p. 82 - 92
(2010/06/16)
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- An expedient route to new spiroheterocycles: Synthesis and structural studies
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We have developed a short, efficient and enantioselective synthesis of 1,4,7,10-tetraoxa- and 1,7-dioxa-4,10-dithiaspiro[5.5]undecanes. The method involved the reaction of solketal 5 or thiol derivative 6 with 1,3-dichloropropanone O-benzyloxime (4) which
- Goubert, Marlene,Canet, Isabelle,Sinibaldi, Marie-Eve
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p. 4805 - 4812
(2007/10/03)
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- Asymmetric synthesis of orthogonally protected (2S,4R)- and (2S,4S)-4-hydroxyornithine
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Synthesis of orthogonally protected (2S, 4R)- and (2S, 4S)-4-hydroxyornithine was reported featuring an asymmetric alkylation of N-(diphenylmethylene)glycine tert-butyl ester (6) by (5S)-N-benzyloxycarbonyl-5-iodomethyl oxazolidine (7). Double stereoselection was examined using chiral ammonium salts as phase transfer catalysts and a substrate-directed chiral induction is documented.
- Lépine, Renaud,Carbonnelle, Anny-Claude,Zhu, Jieping
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p. 1455 - 1458
(2007/10/03)
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- Nucleophilic reaction of glycidol tosylate and the corresponding cyclic sulfate with various nucleophiles: A comparative study
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The nucleophilic reaction of glycidol tosylate and the corresponding cyclic sulfate tosylate have been carried out with a number of nucleophiles to study the possible attack of nucleophiles at C1, C2 or C3 positions. The regioselectivity and reactivity of both the substrates i.e. epoxide tosylate 1 and the corresponding cyclic sulfate 2 have been compared and established that under similar conditions cyclic sulfate counterpart shows better regioselectivity and better reactivity than the corresponding epoxide.
- Lohray,Rajesh,Bhushan
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p. 586 - 592
(2007/10/03)
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- Naphthyloxy acetic acid derivatives and a pharmaceutical composition comprising them as an active ingredient
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The naphthyloxyacetic acid derivatives of the formula (I) wherein A is H, -(alkylene)COOR1, -(alkylene)CONR2R3, -(alkylene)OH, -(alkylene)tetrazole, -(alkylene)CN; E is single bond or alkylene; G is —S—, —SO—, —SO2—, —O— or —NR4—; L is alkylene, —(CH2)m—CH═CH—(CH2)n— or —(CH2)x—CH(OH)—(CH2)y—; M is phenyl, phenyl(thio, oxy, amino), diphenylmethyl, diphenylmethyl(thio, oxy, amino), and pharmaceutical composition comprising them as an active ingradient. The compounds of the formula (I) can combine PGE2receptor and exhibit the activity to antagonize or agonize for PGE2receptor. Therefore, they are useful as anti-hyperlipemia, for the prevention of abortion, for analgesics, as antidiarrheals, sleep inducer, diuretic, anti-diabetes, abortient, cathartics, antiulcer, anti-gastritis or antihypertensive etc.
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Referential example 6
(2010/11/29)
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- Polymer-aided stereodivergent synthesis (PASS): A new concept for the discrete preparation of optical antipodes
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A new concept to the discrete prepartion of optical antipodes is reported. The approach makes use of a cyclization/cleavage procedure that has been applied to polymer-supported quasi-meso compound 1, containing a polymeric leaving group and a regular leaving group. Two-directional cyclization leads to the formation and separation of quasi-enantiomers 2 and 3 simultaneously, with one being immobilized and on free in solution. Treatment of 2 and 3 with appropriate nucleophiles gives discrete enantiomers 4 and 5.
- Ten Holte, Peter,Thijs, Lambertus,Zwanenburg, Binne
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p. 1093 - 1095
(2007/10/03)
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- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
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This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
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- Synthesis of (S)-1-(2',3'-dihydroxypropyl)-2-alkylthiouracils as new antiviral agents
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2-Alkylthiouracils 1a-f have been prepared. Nucleoside coupling of 2 with sodium salt of 1a-f gave the corresponding dioxolane derivatives 3a-f which were treated with 80% acetic acid at reflux temperature to give (S)-1- (2',3'-dihydroxypropyl)-2-alkylthiouracil derivatives 4a-f. Treatment of 4d with 1 mol tosyl chloride gives the corresponding monotosylate 5. On the other hand, with 2 mol it gives the ditosylate 6. Treatment of 5 and/or 6 with sodium azide/dimethylformamide give 7 and 8 which could be reduced to the corresponding amino derivatives 9 and 10 by using triphenylphosphine/pyridine.
- Abdel Rahman,Abdel Aal
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p. 377 - 380
(2007/10/03)
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- Syntheses of L-threose and D-erythrose analogues modified at position 2
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2-O-Methyl-D-erythrose, 2-O-methyl-L-threose, 2-deoxy-D- and L- erythrose, and the corresponding acetonides have been prepared from the commercially available D-isoascorbic and L-ascorbic acids. The proportion of cyclic (α and β furanoses) and acyclic (aldehyde and hydrate) forms was determined in aqueous (D2O) solution by 1H and 13C NMR spectroscopy.
- Andre, Corinne,Bolte, Jean,Demuynck, Colette
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p. 1359 - 1367
(2007/10/03)
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- Syntheses of 4-deoxy-D-fructose and enzymatic affinity study
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Enantiomerically pure 4-deoxy-D-fructose has been prepared and characterised in a protected form, acidic hydrolysis of which led to an aqueous solution of 4-deoxy-D-fructose. Activities of this compound with enzymes of the glycolysis pathway involved in glucose metabolism make possible access to 4-deoxy-D-fructose-6-phosphate, 4-deoxy-D-glucose-6- phosphate and 4-deoxy-D-gluconate-6-phosphate.
- Andre, Corinne,Bolte, Jean,Demuynck, Colette
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p. 3737 - 3739
(2007/10/03)
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- Assignment of the stereochemistry of spiroxamine by two-dimensional NMR spectroscopy and stereoselective chemical synthesis
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Spiroxamine is a new powdery mildew fungicide in cereals consisting of four biologically active isomers (two diastereomers, four enantiomers). The four isomers were separated by preparative high-performance liquid chromatography (HPLC) on a chiral stationary phase. At this stage it was not possible to assign their stereochemistry. Using stereoselective synthesis starting with the corresponding chirally pure glycerol derivates, the configuration at the asymmetric center, could be fixed. The resulting diastereomers were separated by preparative HPLC. Using COSY, HSQC and NOESY NMR spectroscopy it was possible to assign the configuration of the amino residue relative to the cyclohexyl ring. The 600 MHz 1H NMR spectra permitted a complete assignment of all proton signals. The stereochemical assignment is based on NOEs observed in the NOESY spectrum.
- Etzel,Gau,Kraemer,Stelzer,Weissmueller
-
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- Mild and efficient preparation of alkynepentacarbonyldicobalt complexes containing the chiral (R) -(+) -Glyphos ligand
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A range of diastereomeric alkynepentacarbonyldicobalt complexes containing the (R)-(+)-Glyphos ligand have been prepared in moderate to good yields under standard thermal conditions. Additionally, novel tertiary amine N-oxide mediated reactions have been developed which allow the synthesis of the same range of complexes at room temperature with good selectivity in consistently high yields. Optically pure (R)-(+)-Glyphos containing complexes have been obtained by preparative HPLC separation of the sets of diastereomeric compounds. Finally, the amine N-oxide techniques allow the rapid and clean preparation of alkynepentacarbonyltriphenylphosphinedicobalt complexes in good to high yields at room temperature.
- Kerr, William J.,Kirk, George G.,Middlemiss, David
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- Studies on agents with vasodilator and β-blocking activities. III synthesis and activity of optical isomers of TZC-1370
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Optical isomers of TZC-1370 (1) were prepared from (R)- and (S)-1-(2- chlorophenoxy)-2,3-epoxypropane. When given intravenously to anesthetized rats, the (S)-isomer was about 40 times more potent in terms of β-blocking activity than the (R)-isomer, while
- Seki,Takezaki,Ohuchi,Saitoh,Ishimori,Yasuda
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p. 1719 - 1723
(2007/10/03)
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- Diastereo- and Enantioselective Routes to Some 2,8-Dimethyl-1,7-dioxaspiroundecanols. Absolute Stereochemistry of (E,E,E)-2,8-dimethyl-1,7-dioxaspiroundecan-3-ol and of ((E,E)-8-methyl-1,7-dioxaspiroundecan-2-yl)methanol Present in Bactroce
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Routes to the four regioisomeric 2,8-dimethyl-1,7-dioxaspiroundecanols have been developed, and in the racemic series, mercury(II)-mediated reactions of appropriate dienone, hydroxy enone, dienedione, and hydroxy dienone systems have been exploited.M
- Perkins, Michael V.,Jacobs, Mark F.,Kitching, William,Cassidy, Peter J.,Lewis, Judith A.,Drew, Richard A. I.
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p. 3365 - 3380
(2007/10/02)
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- Synthesis and antimuscarinic properties of some N-substituted 5- (aminomethyl)-3,3-diphenyl-2(3H)-furanones
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In a study aimed toward developing new, selective antimuscarinic drugs with potential utility in the treatment of urinary incontinence associated with bladder muscle instability, a series of N-substituted 5-(aminomethyl)- 3,3-diphenyl-2(3H)-furanones, conformationally-constrained lactone relatives of benactyzine, was prepared. The compounds were examined in several paradigms that measure muscarinic (M1, M2, and M3) receptor antagonist activity. Selected members of the series that displayed potency and/or selectivity in these tests were studied for their effects on urinary bladder contraction, mydriasis, and salivation in guinea pigs. These studies revealed that incorporation of the amino functionality into an imidazole or pyrazole ring resulted in some novel, potent, and selective antimuscarinic agents. Appropriate alkyl substitution of position 2 of the imidazole strikingly affected muscarinic, particularly M3, receptor activity and may reflect a complementary site of interaction. Some of the compounds selectively reduced bladder pressure in a cystometrogram (CMG) model without producing concomitant mydriatic and salivary effects. The separate and distinct action of several compounds of this series in these in vivo protocols suggests the possibility of subtypes of muscarinic receptors that may correspond to previously characterized molecular cloned subpopulations. In this article, structure-activity relationships for the series of substituted lactones are discussed. These studies led to the identification of (R)-[(2-isopropyl-1H- imidazol-1-yl)methyl]-4,5-dihydro-3,3-diphenyl-2(3H)-furanone (23) as a clinical candidate for treating urinary bladder dysfunction.
- Kaiser,Spagnuolo,Adams Jr.,Audia,Dupont,Hatoum,Lowe,Prosser,Sturm,Noronha-Blob
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p. 4415 - 4424
(2007/10/02)
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- Enantiomeric Recognition of Organic Ammonium Salts by Chiral Dialkyl-, Dialkenyl-, and Tetramethyl-Substituted Pyridino-18-crown-6 and Tetramethyl-Substituted Bis-pyridino-18-crown-6 Ligands: Comparison of Temperature-Dependent 1H NMR and Empirical Force
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Six new chiral pyridino-18-crown-6 and one chiral bis-pyridino-18-crown-6 ligands have been prepared.The pyridino-crowns contain either two isopropyl, two isobutyl, two (S)-sec-butyl, two benzyl, two 3-butenyl, or four methyl substituents on chiral macror
- Bradshaw, Jerald S.,Huszthy, Peter,McDaniel, Christopher W.,Zhu, Cheng Y.,Dalley, N. Kent,et al.
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p. 3129 - 3137
(2007/10/02)
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- Synthesis of both the enantiomers of 4-dodecanolide, the pheromone of the rove beetle
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A simple and efficient synthesis of the target pheromone in its enantiomeric forms has been formulated using easily accessible (R)-2,3- isopropanedioxyglyceraldehyde (2) as the single starting chiron.
- Chattopadhyay,Mamdapur,Chadha
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p. 3667 - 3672
(2007/10/02)
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- A simple synthesis of the queen substance of oriental hornet, Vespa orientalis from (R)-2,3-O-isopropylideneglycerol
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(R)- and (S)-5-Hexadecanolides I have been synthesized in high optical purity using (R)-2,3-O-isopropylideneglycerol 1 as the chiral source.Stereoisomerization of 1,2-diol 3, Grignard coupling, regioselective Grignard reaction and oxidative cleavage of olefin are some of the key steps involved in it.
- Chattopadhyay, S.,Mamdapur, V. R.,Chadha, M. S.
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p. 108 - 111
(2007/10/02)
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- PRACTICAL ROUTE TO BOTH (S)- AND (R)-ENANTIOMERS OF O-(4-METHOXYPHENYL)GLYCIDOL USING (S)-1,2-O-ISOPROPYLIDENEGLYCEROL AS A COMMON PRECURSOR
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Practical route to both (R)- and (S)-enantiomers of O-(4-methoxyphenyl)glycidol is devised using (S)-1,2-O-isopropylideneglycerol as a common chiral starting material.
- Takano, Seiichi,Moriya, Minoru,Suzuki, Mahito,Iwabuchi, Yoshiharu,Sugihara, Takumichi,Ogasawara, Kunio
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p. 1555 - 1563
(2007/10/02)
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- Synthesis and antiarrhythmic activity of new 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1H-imidazoles and related compounds
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Various 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1H-azoles were synthesized and investigated for β-adrenoceptor-blocking and antiarrhythmic activities. Although no compounds showed more potent β-blocking effects than propranolol in the isolated guinea pig right atria, many compounds exhibited significant antiarrhythmic effects against aconitine or ischemic arrhythmia in mice or dogs. 1-[2,5-Dichloro-6-[1-(1H-imidazol-1-yl)ethenyl]phenoxy]-3-[(1-methylethyl) amino]-2-propanol hydrochloride (48) (711389-S) was selected as a candidate for clinical evaluation in man, since its antiarrhythmic effects were superior to those of quinidine, disopyramide, or propranolol. Asymmetric synthesis of (R)-(+)- and (S)-(-)-48 is described, and it is proven that there is no stereospecificity in the antiarrhythmic effect of 48.
- Ogata,Matsumoto,Takahashi,Shimizu,Kida,Ueda,Kimoto,Haruna
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p. 1142 - 1149
(2007/10/02)
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- Practical Syntheses of - and -1-Alkylamino-3-aryloxy-2-porpanols from a Single Carbohydrate Precursor
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A practical synthetic route to optically active - and -1-alkylamino-3-aryloxy-2-propanols (β-blockers) from -2,3-O-isopropylideneglyceraldehyde (-1) was developed.Synthesis of the -isomers was carried out as follows.Borohydride reduction of -1 in the presence of excess alkylamine followed by alkoxycarbonylation, acid hydrolysis, and cyclization under K2CO3 catalysis gave -3-alkyl-5-hydroxymethyl-1,3-oxazolidin-2-ones, the tosylates of which were coupled with various phenols then hydrolyzed by alkali treatment to give -(-)-β-blockers (e.g., propranolol, carteolol) in satisfactory yields. -,-, and rac-pindolol were synthesized from the corresponding 3-isopropyl-5-(2-methyl-3-nitrophenoxymethyl)-1,3-oxazolidin-2-one by application of the Leimgruber-Batcho method.Keywords--- and -1-alkylamino-3-aryloxy-2-propanols; optically active β-blockers; propranolol; carteolol; pindolol; carbohydrate precursor; -2,3-O-isopropylideneglyceraldehyde; -3-alkyl-5-hydroxymethyl-1,3-oxazolidin-2-ones; Leimgruber-Batcho indole synthesis
- Tsuda, Yoshisuke,Yoshimoto, Kimihiro,Nishikawa, Terumi
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p. 3593 - 3600
(2007/10/02)
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