- SYNTHESIS OF COLLETOCHLORIN D
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An efficient three-step synthesis of Colletochlorin D from orcinol has been achieved.
- Chen, Kau-Ming,Joullie, Madeleine M.
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Read Online
- Synthesis, biological, and photophysical studies of molecular rotor-based fluorescent inhibitors of the trypanosome alternative oxidase
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We have recently reported on the development and trypanocidal activity of a class of inhibitors of Trypanosome Alternative Oxidase (TAO) that are targeted to the mitochondrial matrix by coupling to lipophilic cations via C14 linkers to enable optimal interaction with the enzyme's active site. This strategy resulted in a much-enhanced anti-parasite effect, which we ascribed to the greater accumulation of the compound at the location of the target protein, i.e. the mitochondrion, but to date this localization has not been formally established. We therefore synthesized a series of fluorescent analogues to visualize accumulation and distribution within the cell. The fluorophore chosen, julolidine, has the remarkable extra feature of being able to function as a viscosity sensor and might thus additionally act as a probe of the cellular glycerol that is expected to be produced when TAO is inhibited. Two series of fluorescent inhibitor conjugates incorporating a cationic julolidine-based viscosity sensor were synthesized and their photophysical and biological properties were studied. These probes display a red emission, with a high signal-to-noise ratio (SNR), using both single- and two-photon excitation. Upon incubation with T. brucei and mammalian cells, the fluorescent inhibitors 1a and 2a were taken up selectively in the mitochondria as shown by live-cell imaging. Efficient partition of 1a in functional isolated (rat liver) mitochondria was estimated to 66 ± 20% of the total. The compounds inhibited recombinant TAO enzyme in the submicromolar (1a, 2c, 2d) to low nanomolar range (2a) and were effective against WT and multidrug-resistant trypanosome strains (B48, AQP1-3 KO) in the submicromolar range. Good selectivity (SI > 29) over mammalian HEK cells was observed. However, no viscosity-related shift could be detected, presumably because the glycerol was produced cytosolically, and released through aquaglyceroporins, whereas the probe was located, virtually exclusively, in the trypanosome's mitochondrion.
- Cueto-Díaz, Eduardo J.,Ebiloma, Godwin U.,Alfayez, Ibrahim A.,Ungogo, Marzuq A.,Lemgruber, Leandro,González-García, M. Carmen,Giron, Maria D.,Salto, Rafael,Fueyo-González, Francisco José,Shiba, Tomoo,González-Vera, Juan A.,Ruedas Rama, Maria José,Orte, Angel,de Koning, Harry P.,Dardonville, Christophe
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- Synthesis of natural product-like polyprenylated phenols and quinones: Evaluation of their neuroprotective activities
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Twenty-seven natural product-like polyprenylated phenols and quinones were synthesized and their neuroprotective activity was tested using human monoamine oxidase B (MAO-B) and SH-SY5Y cells. Eight compounds inhibited MAO-B (IC50 values 25 μM
- Kamauchi, Hitoshi,Oda, Takumi,Horiuchi, Kanayo,Takao, Koichi,Sugita, Yoshiaki
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- Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
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A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt2 or LiNiPr2 into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3′-diaryl BINOL ligands is also reported.
- Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
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supporting information
p. 9425 - 9429
(2018/07/29)
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- Unusual polycyclic fused product by oxidative enzymatic dimerisation of 5-methylpyrogallol catalysed by horseradish peroxidase/H2O2
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During investigations on the peroxidase-catalysed oxidation of polyhydroxylated monoaromatic substrates such as 5-methylpyrogallol, we observed a spectacular dimerisation proceeding by dearomatisation in contrast with most common reaction patterns involvi
- Bouges, Hélène,Calabro, Kevin,Thomas, Olivier P.,Antoniotti, Sylvain
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- BORON-CONTAINING SMALL MOLECULES
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Compounds, pharmaceutical formulations, and methods of treating bacterial infections are disclosed.
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Paragraph 0284
(2017/09/19)
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- First total synthesis of kipukasin A
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In this paper, a practical approach for the total synthesis of kipukasin A is presented with 22% overall yield by using tetra-O-acetyl-β-D-ribose as starting material. An improved iodine-promoted acetonide-forming reaction was developed to access 1,2-O-is
- Li, Chuang,Ding, Haixin,Ruan, Zhizhong,Zhou, Yirong,Xiao, Qiang
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supporting information
p. 855 - 862
(2017/06/20)
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- Synthesis and cytotoxic activities of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(-)-cis-khellactone derivatives that induce apoptosis via the intrinsic pathway
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This study deals with the design and synthesis of a series of novel 4-methoxy-substituted and 5-methyl-substituted (3′S,4′S)-(-)-cis-khellactones. The newly synthesized compounds were characterized by1H nuclear magnetic resonance (NMR),13
- Chen, Jingrun,Liu, Junjie,Cui, Dongxiao,Yan, Chaoqun,Meng, Liqiang,Sun, Liqian,Ban, Shurong,Ge, Rui,Liang, Taigang,Li, Qingshan
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p. 1891 - 1904
(2017/07/06)
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- COMPOUNDS FOR USE AS INHIBITORS OF ALTERNATIVE OXIDASE OR CYTOCHROME BC1 COMPLEX
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The invention provides compounds for use in inhibiting a microbial alternative oxidase (AOX) and/or cytochrome bc1 complex. The invention extends to the use of such inhibitors in agrochemicals and in pharmaceuticals, for treating microbial infe
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Paragraph 0112
(2015/07/27)
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- The natural product brartemicin is a high affinity ligand for the carbohydrate-recognition domain of the macrophage receptor mincle
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We demonstrate that the natural product brartemicin, a newly discovered inhibitor of cancer cell invasion, is a high-affinity ligand of the carbohydrate-recognition domain (CRD) of the C-type lectin mincle. Recent studies have revealed that mincle is a ke
- Jacobsen, Kristian M.,Keiding, Ulrik B.,Clement, Lise L.,Schaffert, Eva S.,Rambaruth, Neela D. S.,Johannsen, Mogens,Drickamer, Kurt,Poulsen, Thomas B.
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supporting information
p. 647 - 652
(2015/04/27)
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- 1 -HYDROXY-BENZOOXABOROLES AS ANTIPARASITIC AGENTS
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Provided are compounds useful for controlling endoparasites both in animals and agriculture. Further provided are methods for controlling endoparasite infestations of an animal by administering an effective amount of a compound as described above, or a pharmaceutically acceptable salt thereof, to an animal, as well as formulations for controlling endoparasite infestations using the compounds described above or an acceptable salt thereof, and an acceptable carrier. The claimed compounds are described by the following Markush formula:A typical example for a compound according to above formula is: A typical example for a compound according to above formula is:
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Page/Page column 113-114
(2014/10/03)
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- COMPOUNDS FOR USE AS INHIBITORS OF ALTERNATIVE OXIDASE OR CYTOCHROME BC1 COMPLEX
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The invention provides compounds for use in inhibiting a microbial alternative oxidase (AOX) and/or cytochrome bc1 complex. The invention extends to the use of such inhibitors in agrochemicals and in pharmaceuticals, for treating microbial infe
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Page/Page column 24
(2013/11/18)
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- Total synthesis of graphislactone G
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We present a total synthesis of the fungal natural product graphislactone G, a chlorinated resorcylic lactone. The key step is a Suzuki coupling used for the construction of the central biaryl bond. Graphislactone G was prepared in 13 steps with 22% yield
- Cudaj, Judith,Podlech, Joachim
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supporting information; experimental part
p. 3092 - 3094
(2010/07/18)
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- Benzimidazole Derivatives
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Novel compounds of the formula I (I), in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R, Q, W,
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Page/Page column 12
(2010/02/17)
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- MACROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF KINASES AND HSP90
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Disclosed are macrocyclic compounds of formulae I-V,which are analogs of the pochonin resorcylic acid lactones, and processes for the preparation of the compounds. The compounds disclosed are useful as inhibitors of kinases and Heat Shock Protein 90 (HSP 90). Also disclosed are pharmaceutical compositions comprising an effective kinase-inhibiting amount or an effective HSP90-inhibiting amount of the compounds and methods for the treatment of disorders that are mediated by kinases and HSP90.
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Page/Page column 114; 144
(2010/11/30)
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- Total synthesis of CRM646-A and -B, two fungal glucuronides with potent heparinase inhibition activities
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CRM646-A (1) and -B (2), two fungal glucuronides with a dimeric 2,4-dihydroxy-6-alkylbenzoic acid (orcinol p-depside) aglycone showing significant heparinase and telomerase inhibition activities, were synthesized for the first time. The successful approac
- Wang, Ping,Zhang, Zhaojun,Yu, Biao
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p. 8884 - 8889
(2007/10/03)
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- Solution- and solid-phase synthesis of radicicol (monorden) and pochonin C
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A modular synthesis for pochonin C and radicicol is reported. The two natural products were prepared in seven and eight steps, respectively, from three readily available fragments. Alternative syntheses of these compounds were achieved using a combination of polymer-bound reagents and solid phase reactions. The conformation of the two natural products was studied and compared by using 2D NMR spectroscopy.
- Barluenga, Sofia,Moulin, Emilie,Lopez, Pilar,Winssinger, Nicolas
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p. 4935 - 4952
(2007/10/03)
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- A new and efficient method for o-quinone methide intermediate generation: Application to the biomimetic synthesis of the benzopyran derived natural products (±)-lucidene and (±)-alboatrin
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Lucidene and alboatrin are complex benzopyran derived natural products. A key step in their biogenesis may involve a hetero Diels-Alder cycloaddition between an o-quinone methide intermediate with a simple, or activated tri-substituted olefin. Experimental evidence is provided to support this hypothesis, with the biomimetic synthesis of both (±)-lucidene and (±)-alboatrin successfully achieved using a new and efficient method for o-quinone methide generation. The Royal Society of Chemistry 2005.
- Rodriguez, Raphael,Moses, John E.,Adlington, Robert M.,Baldwin, Jack E.
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p. 3488 - 3495
(2007/10/03)
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- TOTAL SYNTHESIS OF DAURICHROMENIC ACID
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The present invention provides a method to prepare 2H-benzo[6]pyrans, such as the anti-HIV natural product daurichromenic acid (1a), by microwave-assisted tandem aldol reaction of a phenolic enolate followed by intramolecular SN2' type cyclization to form the 2H-benzo[6]pyran core structure.
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Page 2/2; 10
(2008/06/13)
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- A new and efficient method for o-quinone methide intermediate generation: Application to the biomimetic synthesis of (±)-Alboatrin
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(Chemical Equation Presented) A new and efficient method for o-quinone methide intermediate generation from o-methyleneacetoxy-phenols has been developed and applied to the biomimetic synthesis of (±)-Alboatrin.
- Rodriguez, Raphael,Adlington, Robert M.,Moses, John E.,Cowley, Andrew,Baldwin, Jack E.
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p. 3617 - 3619
(2007/10/03)
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- Biologically active 1,3-bis-aromatic-prop-2-en-1-ones, 1,3-bis-aromatic-propan-1-ones, and 1,3-bis-aromatic-prop-2-yn-1-ones
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The invention relates to the use of 1,3-bis-aromatic-prop-2-en-1-ones (chalcones), 1,3-bis-aromatic-propan-1-ones (dihydrochalcones), and 1,3-bis-aromatic-prop-2-yn-1-ones for the preparation of pharmaceutical compositions for the treatment or prophylaxis of a number of serious diseases including i) conditions relating to harmful effects of inflammatory cytokines, ii) conditions involving infection by Helicobacter species, iii) conditions involving infection by viruses, iv) neoplastic disorders, and v) conditions caused by microorganisms or parasites. The invention also relates to novel chalcones and dihydrochalcones (especially alkoxy substituted variants) having advantageous substitution patterns with respect to their effect as drug substances, and to methods of preparing them, as well as to pharmaceutical compositions comprising the novel chalcones. Moreover, the present invention relates to a method for the isolation of Leishmania fumarate reductase, QSAR methodologies for selecting potent compounds for the above-mentioned purposes.
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- Total Synthesis of the Highly Potent Anti-HIV Natural Product Daurichromenic Acid along with Its Two Chromane Derivatives, Rhododaurichromanic Acids A and B
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(Equation presented) The highly potent anti-HIV natural product daurichromenic acid was successfully synthesized in only five steps with 49% overall yield. The key step in the synthetic strategy involves a microwave-assisted tandem condensation and intramolecular SN2′- type cyclization to form the 2H-benzopyran core structure.
- Kang, Ying,Mei, Yan,Du, Yuguo,Jin, Zhendong
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p. 4481 - 4484
(2007/10/03)
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- Anti-AIDS agents. 42. Synthesis and anti-HIV activity of disubstituted (3′R,4′R)-3′,4′-di-O-(S)-camphanoyl-(+)-cis- khellactone analogues
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A series of disubstituted 3′,4′-di-O-(S)-camphanoyl-(+)-cis-khellactone (DCK) analogues (1-10) were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 5-Methoxy-4-methyl DCK (8) was the most promising compound with an EC50 value of 7.21 × 10-6 μM and a therapeutic index of >2.08 × 10,7 which were much better than those of lead compound DCK in the same assay. Another six disubstituted DCK analogues (1-5 and 7) were more potent than AZT but less active than DCK. Conformational analysis suggested that resonance of the coumarin system is an essential structural feature for potent anti-HIV activity. Steric compression of C(4) and C(5) substituents of the coumarin moiety can reduce the overall planarity and thus resonance of the coumarin nucleus, resulting in a decrease or lack of anti-HIV activity.
- Xie,Takeuchi,Cosentino,McPhail,Lee
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p. 664 - 671
(2007/10/03)
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- Total synthesis of everninomicin 13,384-1 - Part 1: Synthesis of the A1B(A)C fragment
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The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The (1 → 1-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.
- Nicolaou,Mitchell, Helen J.,Suzuki, Hideo,Rodriguez, Rosa Maria,Baudoin, Olivier,Fylaktakidou, Konstantina C.
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p. 3334 - 3339
(2007/10/03)
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- Anti-AIDS agents. 37. Synthesis and structure-activity relationships of (3'R,4'R)-(+)-cis-khellactone derivatives as novel potent anti-HIV agents
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To explore the structural requirements of (+)-cis-khellactone derivatives as novel anti-HIV agents, 24 monosubstituted 3',4'-di-O-(S)- camphanoyl-(+)-cis-khellactone (DCK) derivatives were synthesized asymmetrically. These compounds included 4 isomeric monomethoxy analogues (3- 6), 4 isomeric monomethyl analogues (7-10), 4 4-alkyl/aryl-substituted analogues (11-14), and 12 4-methyl-(+)-cis-khellactone derivatives (15-26) with varying 3',4'-substituents. These (+)-cis-khellactone derivatives were screened against HIV-1 replication in acutely infected H9 lymphocytes. The results demonstrated that the (3'R,4'R)-(+)-cis-khellactone skeleton, two (S)-(-)-camphanoyl groups at the 3'- and 4'-positions, and a methyl group on the coumarin ring, except at the 6-position, were optimal structural moieties for anti-HIV activity. 3-Methyl- (7), 4-methyl- (8), and 5-methyl- (9) 3',4'- di-O-(S)-camphanoyl-(3'R,4'R)-(+)-cis-khellactone showed EC50 and therapeutic index values of -5 μM and >2.15 x 106, respectively, in H9 lymphocytes, which are much better than those of DCK and AZT in the same assay. Furthermore, 8 and 9 also showed potent inhibitory activity against HIV-1 replication in the CEM-SS cell line, and most monosubstituted DCK analogues were less toxic than DCK in both assays.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2662 - 2672
(2007/10/03)
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- Stereocontrolled synthesis of the everninomicin A1B(A)C ring framework
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A strategy based on a ring-closing olefin metathesis was used to convert divinylmethanol into 1, which served as a common precursor to activated derivatives 2 and 3. These in turn serve as precursors to the C and B carbohydrate units of the A1B
- Nicolaou,Rodriguez, Rosa M.,Mitchell, Helen J.,Van Delft, Floris L.
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p. 1874 - 1876
(2007/10/03)
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- Anti-AIDS agents 33.1 Synthesis and anti-HIV activity of mono-methyl substituted 3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (DCK) analogues
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Four isomeric methyl substituted DCK analogues (2-5) were asymmetrically synthesized from different starting materials. 3-Methyl, 4-methyl, and 5- methyl-3',4'-di-O-(-)-camphanoyl-(+)-cis-khellactone (2 -4) all were extremely potent against HIV-1 replication in H9 lymphocyte cells with EC50 and therapeutic index values of -7 μM and >3.72 x 108, respectively, which are much better than those of DCK and AZT in this assay.
- Xie, Lan,Takeuchi, Yasuo,Cosentino, L. Mark,Lee, Kuo-Hsiung
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p. 2151 - 2156
(2007/10/03)
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- Antileishmaniai chalcones: Statistical design, synthesis, and three- dimensional quantitative structure-activity relationship analysis
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A large number of substituted chalcones have been synthesized and tested for antileishmanial and lymphocyte-suppressing activities. A subset of the chalcones was designed by using statistical methods. 3D-QSAR analyses using 67 (antileishmanial activity) and 63 (lymphocyte-suppressing activity) of the compounds for the training sets and 9 compounds as an external validation set were performed by using the GRID/GOLPE methodology. The Smart Region Definition procedure with subsequent region selection as implemented in GOLPE reduced the number of variables to approximately 1300 yielding 3D-QSAR models of high quality (lymphocyte-suppressing model, R2 = 0.90, Q2 = 0.80; antileishmanial model, R2 = 0.73, Q2 = 0.63). The coefficient plots indicate that steric interactions between the chalcones and the target are of major importance for the potencies of the compounds. A comparison of the coefficient plots for the antileishmanial effect and the lymphocyte- suppressing activity discloses significant differences which should make it possible to design chalcones having a high antileishmanial activity without suppressing the proliferation of lymphocytes.
- Nielsen, Simon Feldb?k,Christensen, S?ren Br?gger,Cruciani, Gabriele,Kharazmi, Arsalan,Liljefors, Tommy
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p. 4819 - 4832
(2007/10/03)
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- Asymmetric synthesis of orsellinic acid type macrolides: The example of lasiodiplodin
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The asymmetric synthesis of both enantiomers of methyl lasiodiplodin is described. The chiral centers were created in the very last steps of the synthesis by asymmetric induction of a chiral sulfoxide group.
- Solladie,Rubio,Carreno,Ruano
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p. 187 - 198
(2007/10/02)
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- A CONVENIENT SYNTHESIS OF (+/-) ASCOCHLORIN
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A convergent total synthesis of (+/-) ascochlorin is described.
- Safaryn, J. E.,Chiarello, J.,Chen, K.-M.,Joullie, M. M.
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p. 2635 - 2642
(2007/10/02)
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- Total Syntheses of Fungal Metabolites and Functionalized Furanones
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Simple, efficient syntheses of the fungal metabolites colletochlorin D and (+/-)-ascofuranone and one of its stereoisomers are described.Our investigations of functionalized furanones also enabled us to develop a nine-step (22percent overall yield) synthe
- Chen, Kau-Ming,Semple, J. Edward,Joullie, Madeleine M.
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p. 3997 - 4005
(2007/10/02)
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