- Stereoselective Synthesis of Baulamycin A
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New structural classes of antibiotics are rare, structurally novel broad-spectrum antibiotics exceptionally so. The recently discovered baulamycins constitute a remarkable example of these highly prized compounds and, as such, have attracted considerable attention in the form of both synthetic efforts and biological studies. For the first time, we report a gram-scale preparation of the common carbon framework of the baulamycin family, as well as the total synthesis of its most potent member, baulamycin A. Our approach employs highly stereoselective, catalyst-controlled asymmetric conjugate additions to thioesters to set key stereocenters, as well as the first reported use of "dry ozonolysis" to reveal a masked carboxylic acid in the total synthesis of a natural product.
- Sherman, David H.,Thielman, Jonathan R.,Williams, Robert M.
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p. 3812 - 3823
(2020/03/23)
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- Structural Revision of Baulamycin A and Structure-Activity Relationships of Baulamycin A Derivatives
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Total synthesis of the proposed structure of baulamycin A was performed. The spectral properties of the synthetic compound differ from those reported for the natural product. On the basis of comprehensive NMR study, we proposed two other possible structur
- Sengupta, Sandip,Bae, Munhyung,Oh, Dong-Chan,Dash, Uttam,Kim, Hak Joong,Song, Woon Young,Shin, Injae,Sim, Taebo
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p. 12947 - 12966
(2017/12/26)
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- Structure and Spectroscopy of Alkene-Cleaving Dioxygenases Containing an Atypically Coordinated Non-Heme Iron Center
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Carotenoid cleavage oxygenases (CCOs) are non-heme iron enzymes that catalyze scission of alkene groups in carotenoids and stilbenoids to form biologically important products. CCOs possess a rare four-His iron center whose resting-state structure and inte
- Sui, Xuewu,Weitz, Andrew C.,Farquhar, Erik R.,Badiee, Mohsen,Banerjee, Surajit,Von Lintig, Johannes,Tochtrop, Gregory P.,Palczewski, Krzysztof,Hendrich, Michael P.,Kiser, Philip D.
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p. 2836 - 2852
(2017/06/13)
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- Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: Synthesis and the structure-activity relationship
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To explore the structure-activity relationships on the inhibitory activity of flavanonols against nitric oxide (NO) production in inflammatory cells, we synthesized 19 flavanonols which shared a common 3,5,7-trihydroxychroman scaffold. A range of substitutions was included in the B ring in order to investigate the structure-activity relationship. We also succeeded in isolating stereoisomers from 16 of the flavanonols using chiral column chromatography. The inhibitory effects of these compounds on NO production were examined in RAW 264.7 cells (a murine macrophage-like cell line), which were activated by lipopolysaccharide (LPS). We only observed inhibitory activity against NO production in (2R,3R) stereoisomers, while the inhibitory activities of (2S,3S) stereoisomers were significantly weaker. We also evaluated the free radical scavenging potential of the flavanonols using 1,1-diphenyl-2-picrylhydrazyl (DPPH). Each stereoisomer indicated the equivalent DPPH scavenging potential as expected. The radical scavenging activity was not correlated with the inhibitory activity against NO. The inhibition of NO production by flavanonols is stereospecific and cannot simply be explained by their radical scavenging activity. We propose the possible existence of a 'target' molecule for flavanonols which is involved in the production and/or regulation of NO in RAW 264.7 cells.
- Jiang, Wen-Jun,Ishiuchi, Kan'Ichiro,Furukawa, Megumi,Takamiya, Tomoko,Kitanaka, Susumu,Iijima, Hiroshi
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p. 6922 - 6929
(2015/11/11)
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- New multi-target-directed small molecules against Alzheimer's disease: A combination of resveratrol and clioquinol
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Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the 'multi-target-directed ligands' (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced β-amyloid (Aβ) aggregation and copper(ii)-induced Aβ aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9-3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced Aβ aggregation (IC50 = 8.50 μM) and copper(ii)-induced Aβ aggregation and to disassemble the well-structured Aβ fibrils generated by self- and copper(ii)-induced Aβ aggregation. Note that 10c could also control Cu(i/ii)-triggered hydroxyl radical (OH) production by halting copper redox cycling via metal complexation, as confirmed by a Cu-ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg-1 and was able to cross the blood-brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD. This journal is the Partner Organisations 2014.
- Mao, Fei,Yan, Jun,Li, Jianheng,Jia, Xian,Miao, Hui,Sun, Yang,Huang, Ling,Li, Xingshu
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supporting information
p. 5936 - 5944
(2014/08/05)
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- Scope and limitations of the Heck-Matsuda-coupling of phenol diazonium salts and styrenes: A protecting-group economic synthesis of phenolic stilbenes
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4-Phenol diazonium salts undergo Pd-catalyzed Heck reactions with various styrenes to 4′-hydroxy stilbenes. In almost all cases higher yields and fewer side products were observed, compared to the analogous 4-methoxy benzene diazonium salts. In contrast, the reaction fails completely with 2- and 3-phenol diazonium salts. For these substitution patterns the methoxy-substituted derivatives are superior. The Royal Society of Chemistry 2013.
- Schmidt, Bernd,Elizarov, Nelli,Berger, René,H?lter, Frank
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supporting information
p. 3674 - 3691
(2013/06/27)
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- 3,5,2′,4′-Tetrahydroxychalcone, a new non-purine xanthine oxidase inhibitor
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Xanthine oxidase is a key enzyme that catalyses hypoxanthine and xanthine to uric acid and the overproduction of uric acid will lead to hyperuricemia which is an important cause of gout. In the present study, three chalcone derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, only Compound 1, 3,5,2′,4′-tetrahydroxychalcone, exhibited a significant inhibitory activity on xanthine oxidase with an IC50 value of 22.5 μM. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that it was a competitive inhibitor of xanthine oxidase and Ki value was 17.4 μM. In vivo, intragastric administration of Compound 1 was able to significantly reduce serum uric acid levels and inhibited hepatic xanthine oxidase activities of hyperuricemic mice in a dose-dependent manner. Acute toxicity study in mice showed that Compound 1 was very safe at a dose of up to 5 g/kg. These results suggest that Compound 1 is a novel competitive xanthine oxidase inhibitor and is worthy of further development.
- Niu, Yanfen,Zhu, Huajie,Liu, Jia,Fan, Huafang,Sun, Ling,Lu, Wei,Liu, Xu,Li, Ling
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scheme or table
p. 161 - 166
(2012/01/11)
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- Phenolic bis-styrylbenzenes as β-amyloid binding ligands and free radical scavengers
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Starting from bisphenolic bis-styrylbenzene DF-9 (4), β-amyloid (Aβ) binding affinity and specificity for phenolic bis-styrylbenzenes, monostyrylbenzenes, and alkyne controls were determined by fluorescence titration with β-amyloid peptide Aβ1-40 and a fluorescence assay using APP/PS1 transgenic mouse brain sections. Bis-styrylbenzene SAR is derived largely from work on symmetrical compounds. This study is the first to describe Aβ binding data for bis-styrylbenzenes unsymmetrical in the outer rings. With one exception, binding affinity and specificity were decreased by adding and/or changing the substitution pattern of phenol functional groups, changing the orientation about the central phenyl ring, replacing the alkene with alkyne bonds, or eliminating the central phenyl ring. The only compound with an Aβ binding affinity and specificity comparable to 4 was its 3-hydroxy regioisomer 8. Like 4, 8 crossed the blood-brain barrier and bound to Aβ plaques in vivo. By use of a DPPH assay, phenol functional groups with para orientations seem to be a necessary, but insufficient, criterion for good free radical scavenging properties in these compounds.
- Flaherty, Daniel P.,Kiyota, Tomomi,Dong, Yuxiang,Ikezu, Tsuneya,Vennerstrom, Jonathan L.
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supporting information; experimental part
p. 7992 - 7999
(2011/03/19)
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- Efficient and general preparation of pyranostilbenes: First total synthesis of artocarbene and pawhuskin B
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An efficient and general synthesis providing pyranostilbenes in moderate yields has been developed. It consists of the reaction of pinosylvin with the appropriate a,β-unsaturated aldehyde catalyzed by ethylenediamine diacetate. As an application of this m
- Byung, Ho Park,Yong, Rok Lee,Won, Seok Lyoo
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experimental part
p. 2146 - 2154
(2010/02/28)
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- Synthesis and structure revision of the myo-inositol monophosphatase inhibitor l-671,776
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Concomitant deprotection/spiro-heteroannulation of 6 utilizing (EtO)3SiI was exploited for the asymmetric total synthesis of the title tetracyclic terpenoid whose structure was revised to 13.
- Falck,Kishta Reddy,Chandrasekhar
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p. 5245 - 5248
(2007/10/03)
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- Synthesis and Characterization of Doubly-Strapped Porphyrins
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Synthesis of a "doubly-strapped" porphyrin is described, which has two -O(CH2)10O- straps on both sides of the porphyrin ring.This porphyrin did not form the zinc complex when treated with zinc acetate, even under forcing conditions.Such inertness toward
- Nagata, Toshi
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p. 385 - 391
(2007/10/02)
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- Synthesis of Averufin and its Role in Aflatoxin B1 Biosynthesis
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Described are two total syntheses of (+/-)-averufin (4) proceeding through a common intermediate and predicated on the efficient introduction of isotopic label(s) at side-chain and nuclear sites for the purpose of biosynthetic investigations of aflatoxin B1 (8).Using these methods, (+/-)--and --averufin, (65) and (68) respectively, and a 1:1 mixture of (+/-)-- and --averufin (71) were prepared and incorporated into aflatoxin B1 using mycelial suspensions of Aspergillus parasiticus (SU-1).In each instance efficient and specific utilization of label was observed in the product by (13)C-n.m.r.spectroscopy, demonstrating the intact incorporation of averufin.When compared with earlier observations of acetate incorporation, a complete correlation of the carbon skeleton from the intermediate anthraquinone stage of the four carbons lost in this overall process were unambiguously identified.In the formation of the dihydrobisfuran, the anthraquinone nucleus migrates to C-2' to branch the linear side-chain of averufin.Deuterium bound at C-1' in averufin is carried to C-13 of aflatoxin.Preparation from (+/-)-averufin (68) of (+/-)--averufin (73) and incorporation of the latter into versiconal acetate (5) demonstrated loss of the terminal two carbons of the averufin side-chain, presumably as acetate, by way of a Baeyer-Villiger-like oxidation.
- Townsend, Craig A.,Christensen, Siegfried B.,Davis, Steven G.
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p. 839 - 862
(2007/10/02)
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- SYNTHESIS OF HORMOTHAMNIONE
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Hormothamnione 1 has been obtained from 2,3-dimethyl-5,6,7,8-tetramethoxy-chromone 18 in 63percent yield.Synthesis of the required chromone 18 as well as of the 2 and 3-styryl analogs 5 and 9 are described.
- Alonso, Ricardo,Brossi, Arnold
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p. 735 - 738
(2007/10/02)
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- Synthesis of 2'- and 3'-acetoxyolivetols [5-(2- and 3-acetoxypentyl)-1,3-benzenediols]: Key intermediates in the synthesis of tetrahydrocannabinol derivatives
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Generally, the synthesis of side-chain derivatives of THC's has been achieved by condensation of the appropriately substituted olivetol with a monoterpene, e.g., the biologically potent metabolite 3'-hydroxy-Δ1-THC was synthesized from 3'-aceto
- Duffley,Handrick,Uliss,et al.
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p. 733 - 736
(2007/10/02)
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