- Biomimetic photooxidation of noscapine sensitized by a riboflavin derivative in water: The combined role of natural dyes and solar light in environmental remediation
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Noscapine (NSC) is a benzyl-isoquinoline alkaloid discovered in 1930 as an antitussive agent. Recently, NSC has also been reported to exhibit antitumor activity and, according to computational studies, it is able to attack the protease enzyme of Coronavirus (COVID-19) and thus could be used as antiviral for COVID-19 pandemic. Therefore, an increasing use of this drug could be envisaged in the coming years. NSC is readily metabolized with a half-life of 4.5 h giving rise to cotarnine, hydrocotarnine, and meconine, arising from the oxidative breaking of the C–C bond between isoquinoline and phthalide moieties. Because of its potentially increasing use, high concentrations of NSC but also its metabolites will be delivered in the environment and potentially affect natural ecosystems. Thus, the aim of this work is to investigate the degradation of NSC in the presence of naturally occurring photocatalysts. As a matter of fact, the present contribution has demonstrated that NSC can be efficiently degraded in the presence of a derivative of the natural organic dye Riboflavin (RFTA) upon exposure to visible light. Indeed, a detailed study of the mechanism involved in the photodegradation revealed the similarities between the biomimetic and the photocatalyzed processes. In fact, the main photoproducts of NSC were identified as cotarnine and opianic acid based on a careful UPLC-MS2 analysis compared to the independently synthesized standards. The former is coincident with one of the main metabolites obtained in humans, whereas the latter is related to meconine, a second major metabolite of NSC. Photophysical experiments demonstrated that the observed oxidative cleavage is mediated mainly by singlet oxygen in a medium in which the lifetime of 1O2 is long enough, or by electron transfer to the triplet excited state of RFTA if the photodegradation occurs in aqueous media, where the 1O2 lifetime is very short.
- Pavanello, Alice,Fabbri, Debora,Calza, Paola,Battiston, Debora,Miranda, Miguel A.,Marin, M. Luisa
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- Studies on asymmetric total synthesis of (?)-β-hydrastineviaa chiral epoxide ring-opening cascade cyclization strategy
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Herein, facile and enantioselective approaches to synthesize the core phthalide tetrahydroisoquinoline scaffold of (?)-β-hydrastineviaboth a CF3COOH-catalyzed (86% ee) and KHMDS-catalyzed (78% ee) epoxide ring-opening/transesterification cascade cyclization from chiral epoxide under very mild conditions are described. The key elements include a highly enantioselective epoxidation using the Shi ketone catalyst and an intramolecular CF3COOH-catalyzed cascade cyclization in one pot, and a late-stage C-3′ epimerization under MeOK/MeOH conditions as the key steps to achieve the first total synthesis of (?)-β-hydrastine (up to 81% ee).
- Cheng, Maosheng,Li, Jihui,Liu, Yongxiang,Meng, Jiaxin,Qin, Qiaohua,Song, Xinjing,Wu, Tianxiao,Zhao, Dongmei,Zheng, Yang
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p. 18953 - 18958
(2020/06/08)
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- An Acid-Catalyzed Epoxide Ring-Opening/Transesterification Cascade Cyclization to Diastereoselective Syntheses of (±)-β-Noscapine and (±)-β-Hydrastine
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An acid-catalyzed stereoselective epoxide ring-opening/intramolecular transesterification cascade cyclization reaction and N-Boc deprotection was found to be a successful strategy to construct the phthalide tetrahydroisoquinoline skeleton in one pot. Based on this strategy, the unified and highly diastereoselective routes for the total syntheses of (±)-β-Noscapine and (±)-β-Hydrastine were exploited.
- Li, Jihui,Liu, Yongxiang,Song, Xinjing,Wu, Tianxiao,Meng, Jiaxin,Zheng, Yang,Qin, Qiaohua,Zhao, Dongmei,Cheng, Maosheng
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supporting information
p. 7149 - 7153
(2019/09/30)
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- Copper(I) mediated facile synthesis of potent tubulin polymerization inhibitor, 9-amino-α-noscapine from natural α-noscapine
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Facile synthesis of natural α-noscapine analogue, 9-amino-α-noscapine, a potent inhibitor of tubulin polymerization for cancer therapy, is achieved via copper(I) iodide mediated in situ aromatic azidation and reduction of 9-bromo-α-noscapine (obtained by bromination of natural α-noscapine) with NaN3 in DMSO at 130 °C in the presence of l-proline as an amino acid promoter. The protocol developed here avoided isolation of 9-azido-α-noscapine and did not cleave the sensitive C-C bond between two heterocyclic phthalide and isoquinoline units.
- Manchukonda, Naresh K.,Sridhar, Balasubramanian,Naik, Pradeep K.,Joshi, Harish C.,Kantevari, Srinivas
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scheme or table
p. 2983 - 2987
(2012/06/15)
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- Syntheses of differentially protected isocoumarins
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Syntheses of an isocoumarin subunit suitable for the completion of purpuromycin are outlined. Specifically, work targeting an orthogonally protected isocoumarin (eventually 12% yield over 12 steps) and an improved synthesis of a symmetrically protected isocoumarin (18% over 10 steps) are described. A new modification for selective catechol protection as mediated by potassium bicarbonate is also presented along with insights into oxidative and reductive functionalization of isocoumarins.
- Lowell, Andrew N.,Wall, Philip D.,Waters, Stephen P.,Kozlowski, Marisa C.
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experimental part
p. 5573 - 5582
(2010/10/01)
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- First Rational Synthesis of the Thiothiono Analogue of an Unsymmetrically Substituted Phthalic Anhydride
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equation presented Treatment of the dithiolane derivative of an α-carboxyethyl benzaldehyde with LDA at -78°C smoothly produced the thiothionophthalic anhydride. The mechanism is proposed to involve loss of ethene and attack of an intermediate dithiocarboxylate onto the ester. Heating the thiothionophthalic anhydride gave the 3,3′-bithiophthalide.
- Morrison, Christopher F.,Burnell, D. Jean
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p. 3891 - 3892
(2007/10/03)
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- Synthesis of saulatine
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A study directed toward the synthesis of saulatine (5,8,9,14a-tetrahydro- 3,4,11,12-tetramethoxy-isoquino[1,2-b]benzazepine-6,14-dione) is described. The successful synthetic route consists of three steps starting with 3,4- dimethoxyphenethylamine and 2-bromo-(3,4-dimethoxy-2- ethoxycarbomethylphenyl)-acetate. It was found that the methoxy moieties present on the aromatic rings prohibit the use of the intramolecular Friedel- Crafts reaction with a Lewis acid catalyst for ring construction because of their demethylation tendency under the reaction conditions.
- Dong Chin Kim,Won Hyung Yoon,Choi,Kim
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p. 1431 - 1436
(2007/10/02)
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- Influence of Alkoxyalkyl Substituents in the Regioselective Lithiation of the Benzene Ring
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The concomitant presence of an alkoxyalkyl group (α-alkoxyalkyl, α- or β-dialkoxyalkyl) and of an alkoxy group in the relative positions 1 and 3 in a benzene ring generally permits an easy lithiation of position 2 by proton-metal exchange with n-butyllithium; the only aromatic compound tested, bearing a β-alkoxyalkyl group, gave, however, extensive decomposition in the metalation step.Reaction of the metalated species with an electrophile (such as carbon dioxide or ethyl chloroformate) leads to the corresponding substituted products in good to excellent yields.The following transformations are described: 3,4-dimethoxybenzyl α-ethoxyethyl ether (1) into 6,7-dimethoxyphthalide (15); 3,4-(methylenedioxy)benzyl α-ethoxyethyl ether (2) into 6,7-(methylenedioxy)phthalide (16); 3,4-dimethoxybenzyl methyl ether (3) into ethyl 2-(methoxymethyl)-5,6-dimethoxybenzoate (18) and into ethyl 2-(chloromethyl)-5,6-dimethoxybenzoate (20); 3,4-(methylenedioxy)benzyl methyl ether (4) into ethyl 2-(methoxymethyl)-5,6-(methylenedioxy)benzoate (19) and into ethyl 2-(chloromethyl)-5,6-(methylenedioxy)benzoate (21); 3,4-dimethoxybenzaldehyde dimethyl acetal (5) into 5,6-dimethoxyphthalaldehydic acid (22); 3,4-(methylenedioxy)benzaldehyde dimethyl acetal (6) into 5,6-(methylenedioxy)phthalaldehydic acid (23); (3,4-dimethoxyphenyl)acetaldehyde dimethyl acetal (7) into ethyl 2-(2,2-dimethoxyethyl)-5,6-dimethoxybenzoate (25); 3,4,4'-trimethoxydeoxybenzoin ethylene acetal (10) into 2-(ethoxycarbonyl)-3,4,4'-trimethoxydeoxybenzoin (26); 4,3',4'-trimethoxydeoxybenzoin ethylene acetal (11) into 2'-(ethoxycarbonyl)-4,3',4'-trimethoxydeoxybenzoin (27); 3,4,3',4'-tetramethoxydeoxybenzoin ethylene acetal (12) into a mixture of 3-(3,4-dimethoxybenzylidene)-6,7-dimethoxyphthalide (28) and 3-(3,4-dimethoxyphenyl)-7,8-dimethoxyisocoumarin (29).The dioxole ring of methylenedioxy-substituted benzenes is sometimes unstable under these metalation conditions, and partial decomposition usually causes the yields to be lower than those in the case of the corresponding methoxy-substituted benzenes.Many of the products listed above, which have been already prepared by other methods, are more conveniently obtained by the present approach.
- Napolitano, Elio,Giannone, Enrico,Fiaschi, Rita,Marsili, Antonio
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p. 3653 - 3657
(2007/10/02)
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