- Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study
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Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68–70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid. 68–70 exhibited good LDH1 and LDH5 inhibitory activities with noncompetitive inhibition type, and were more potent than stiripentol. Notably, 70, as a representative agent, was also shown as a moderately positive allosteric modulator at human α1β2γ2 GABAA receptors (EC50 46.3 ± 7.3 μM). Thus, 68–70 were promising candidates for developing into anti-epileptic drugs, especially for treatment of refractory epilepsies such as Dravet syndrome.
- Bai, Yajun,He, Xirui,Bai, Yujun,Sun, Ying,Zhao, Zefeng,Chen, Xufei,Li, Bin,Xie, Jing,Li, Yang,Jia, Pu,Meng, Xue,Zhao, Ye,Ding, Yanrui,Xiao, Chaoni,Wang, Shixiang,Yu, Jie,Liao, Sha,Zhang, Yajun,Zhu, Zhiling,Zhang, Qiang,Zhao, Yuhui,Qin, Fanggang,Zhang, Yi,Wei, Xiaoyang,Zeng, Min,Liang, Jing,Cuan, Ye,Shan, Guangzhi,Fan, Tai-Ping,Wu, Biao,Zheng, Xiaohui
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- Unanticipated participation of HCl in nucleophilic chlorination reaction: Expedient route to meta chlorophenols
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o-Quinone monoketals participated in a 1,4-addition reaction with HCl furnishing m-chlorophenols in high yields. Several readily available o-quinone monoketals were selected to display the generality of this serendipitous and unprecedented reaction and the results are presented herein.
- Chittimalla, Santhosh Kumar,Bandi, Chennakesavulu
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- Divergent and concise total syntheses of dihydrochalcones and 5-deoxyflavones recently isolated from Tacca species and Mimosa diplotricha
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Dihydrochalcones and 5-deoxyflavones are types of compounds possessing various biologically interesting properties. Herein, we report the concise and divergent total syntheses of several naturally occurring dihydrochalcones and 5-deoxyflavones from readily available starting materials. The divergent strategy is based around manipulation of a common chalcone scaffold and features application of Algar-Flynn-Oyamada oxidation and benzoquinone C-H activation methodologies. These are the first reported total syntheses of these biologically interesting compounds and the concise and flexible route should be readily amenable to future analogue generation. Furthermore, this work provides an illustration of the utility of divergent synthesis for the expedient and step-economical preparation of natural product libraries.
- Sum, Tze Han,Sum, Tze Jing,Stokes, Jamie E.,Galloway, Warren R.J.D.,Spring, David R.
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p. 4557 - 4564
(2015/06/08)
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- Synthesis of polyhydroxylated flavonoids bearing a lipophilic decyl tail as potential therapeutic antioxidants
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Antioxidants have potential for the treatment of stroke and neurodegeneration, and chimeric compounds that combine a flavon-3-ol head group related to myricetin and a lipophilic decyl tail are known to protect membranes from oxidative damage at least as well as vitamin E. New flavon-3-ols that are highly hydroxylated in the B ring in ways not found in natural flavon-3-ols and bearing a lipophilic decyl tail have been prepared from trimethoxy-and tetramethoxybenzoic acids accessed by lithiation-carboxylation reactions. Direct enolate acylation was preferred over Baker-Venkataraman rearrangement when there were methoxy groups at both the 2-and the 6-position of the benzoic acid derivatives.
- Caldwell, Stuart T.,McPhail, Donald B.,Duthie, Garry G.,Hartley, Richard C.
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scheme or table
p. 23 - 33
(2012/03/07)
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- COGNITIVE DISORDER-AMELIORATING AGENT
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A cognitive impairment ameliorant is provided that is useful for the prevention or treatment of cognitive impairment, and particularly Alzheimer's disease. The cognitive impairment ameliorant contains royal jelly as an active ingredient thereof.
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- Toward establishing structure-activity relationships for oxygenated coumarins as differentiation inducers of promonocytic leukemic cells
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The presumption that some coumarins might be lead compounds in the search for new differentiation agents against leukemia is based on the fact that natural coumarins, 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin (C-2) and 5-methoxy-6,7-methylenedioxycoumarin (C-1) inhibit proliferation and induce differentiation in U-937 cells [Riveiro, M. E.; Shayo, C.; Monczor, F.; Fernandez, N.; Baldi, A.; De Kimpe, N.; Rossi, J.; Debenedetti, S.; Davio, C. Cancer Lett. 2004, 210, 179-188]. These promising findings prompted us to investigate the anti-leukemia activity of a broader range of related polyoxygenated coumarins. Twenty related natural or synthetically prepared coumarins, including a range of 5-substituted ayapin derivatives which have become easy accessible via newly developed synthesis methods, were evaluated, where treatments with 5-(2,3-dihydroxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (D-3) and 5-(2-hydroxy-3-methoxy-3-methylbutoxy)-6,7-methylenedioxycoumarin (D-2) were able to inhibit the cell growth and induce the differentiation of U-937 cells after 48 h treatment. These results provide insight into the correlation between some structural properties of polyoxygenated coumarins and their in vitro leukemic differentiation activity.
- Riveiro, Maria E.,Maes, Dominick,Vazquez, Ramiro,Vermeulen, Monica,Mangelinckx, Sven,Jacobs, Jan,Debenedetti, Silvia,Shayo, Carina,De Kimpe, Norbert,Davio, Carlos
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scheme or table
p. 6547 - 6559
(2009/12/09)
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- Total synthesis of naturally occurring 5,6,7- and 5,7,8-trioxygenated coumarins
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The synthesis of five naturally occurring polyoxygenated coumarins is described. It concerns two 5,6,7-trioxygenated coumarins, i.e., 6-hydroxy-5,7-dimethoxycoumarin (fraxinol) 1 and 5,6,7-trimethoxycoumarin 2, and three 5,7,8-trioxygenated coumarins, i.e., 8-hydroxy-5,7-dimethoxycoumarin (leptodactylone) 3, 5,7,8-trimethoxycoumarin 4 and 8-(3-methyl-2-butenyloxy)-5,7-dimethoxycoumarin (artanin) 5. Key feature of the synthetic pathway is the synthesis of suitable tetraoxygenated benzaldehydes, which are then converted to the corresponding coumarins via a Wittig reaction.
- Maes, Dominick,Riveiro, Maria Eugenia,Shayo, Carina,Davio, Carlos,Debenedetti, Silvia,De Kimpe, Norbert
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p. 4438 - 4443
(2008/09/21)
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- Acid catalyzed stereoselective rearrangement and dimerization of flavenes: synthesis of dependensin
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Appropriately substituted flavenes undergo stereoselective rearrangement and dimerization when treated with methanolic hydrochloric acid to give benzopyranobenzopyrans. A rationale for the rearrangement is proposed. This synthetic methodology has been used for a high yield synthesis of the natural product dependensin.
- Deodhar, Mandar,Black, David StC,Kumar, Naresh
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p. 5227 - 5235
(2008/02/01)
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- Miscrowave-assisted efficient synthesis of polymethoxyacetophenones and natural polymethoxyflavones, and thier inhibitory effects on melanogenesis
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Microwave, assisted Friedel-Crafts acetylation of polymethoxybenzenes with acetic anhydride in the presence of In(CF3SO3)3 under solvent-free conditions was achieved rapidly to give polymethoxyacetophenones in high yields. Microwave-assisted benzoylation of 2'-hydroxypolymethoxyacetophenones with polymethoxybenzoyl chlorides, followed by the rearrangement of the resulting benzoates and the final formation of natural polymethoxyflavones was achieved rapidly and efficiently. The polymethoxyflavones showed inhibitory effects on melanogenesis in human melanoma cells.
- Tsukayama, Masao,Kusunoki, Eiji,Hossain, Mohammad M.,Kawamura, Yasuhiko,Hayashi, Shinji
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p. 1589 - 1600
(2008/09/17)
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- Synthesis of 2-aryl- and 2-heteroaryl-3,5-dimethoxy-1,4 -benzoquinones involving Pd-catalyzed cross-coupling of (2,3,4,6-tetramethoxyphenyl)boronic acid
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A series of 2-aryl- and 2-heteroaryl-substituted 3,5-dimethoxy-1,4- benzoquinones (compounds 27-36) have been synthesized by cross-coupling of (2,3,4,6-tetramethoxyphenyl)boronic acid (2) with aromatic bromides or iodides in the presence of [Pd0/sup
- Lana, Enio Jose Leao,Carazza, Fernando,De Oliveira, Rosilene Aparacida
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p. 1825 - 1831
(2007/10/03)
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- Improved, rapid and efficient synthesis of polymethoxyflavones under microwave irradiation and their inhibitory effects on melanogenesis
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The microwave-assisted methylation of 2,5-dihydroxy-1,3-dimethoxybenzene with (CH3O)2SO2 for 5 min gave easily 1,2,3,5-tetramethoxybenzene, which was converted into pentamethoxybenzene. The microwave-assisted Friedel-Crafts acylation of pentamethoxybenzene in the presence of In(CF3SO3)3 gave pentamethoxyacetophenone for 15 min under solvent-free conditions in high yield. The microwave-assisted cyclization reaction of the diketones, which were synthesized from the acetophenone via three steps under microwave irradiation, gave the desired polymethoxyflavones for 1.5-3 min in high yields. The polymethoxyflavones showed inhibitory effects on melanogenesis in a human melanoma.
- Tsukayama, Masao,Kawamura, Yasuhiko,Ishizuka, Takaaki,Hayashi, Shinji,Torii, Fumihito
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p. 2775 - 2784
(2007/10/03)
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- An Improved Synthesis of 1,4-Benzo- and 1,4-Naphthoquinones Bearing Active Substituents
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The synthesis of 1,4-benzoquinones and 1,4-naphthoquinones 3a-j carrying substituents such as methoxyl, allyl or oxiranyl was substantially improved.The 1-methoxy-4-methoxymethyloxy 2a-d, g-k or 1,4-bis(methoxymethyloxy) derivatives 2e-f were used, as a substrates instead of 1,4-dimethoxy derivatives 1a-j hitherto used and they were oxidized with silver(II) dipicolinate.Among numerous examples, the synthesis of a new analog of ubiquinone 3d with the oxiranyl substituent, being a new bioactivated alkylating agent, is reported.
- Syper, Ludwik,Kloc, Krystian,Mlochowski, Jacek
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p. 808 - 822
(2007/10/02)
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- SYNTHESIS OF 5,6'-dihydroxy-2',3',4',6,7-PENTAMETHOXYFLAVONE
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5,6'-Dihydroxy-2',3',4',6,7-pentamethoxy- (1), 2',5-dihydroxy-3',4',6,6',7-pentamethoxy- (2) and 3',5-dihydroxy-2',4',6,6',7-pentamethoxyflavone (3) were synthesized to compare with brickellin isolated from Brickellia veronicaefolia and B. chlorolepis.The
- Iinuma, Munekazu,Iwashima, Kiyoshi,Tanaka, Toshiyuki,Matsuura, Shin
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p. 4217 - 4219
(2007/10/02)
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