Reaction of α,β‐unsaturated ketones using cerium (IV) sulfate tetrahydrate in acetic acid

Itoh, Ken‐ichi; Utsukihara, Takamitsu; Funayama, Kenji; Sakamaki, Hiroshi; Kanamori, Miyuki; Takahashi, Takafumi; Saitoh, Yoshikazu; Matsushita, Masatoshi; He, Liangyou; Hashimoto, Chikao; Sugiyama, Takashi; Horiuchi, C. Akira

doi:10.1002/aoc.1326

Cited by 6 publications

(4 citation statements)

References 14 publications

(12 reference statements)

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“…Yield 52%, White solid, MM: 370.18 g/mol, m.p. : 145–146 °C; 1 H NMR (200 MHz, CDCl 3 ) δ H 7.81 (d, J = 16.0 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.94 (s, 1H), 6.83 (s, 2H), 6.58 (d, J = 16.0 Hz, 1H), 3.91 (s, 9H), 2.91 (Hept, J = 6.0 Hz, 1H), 2.18 (s, 3H), 1.26 (s, 3H), 1.23 (s, 3H), 13 C NMR (50 MHz, CDCl 3 ) δ C 165.3, 153.6, 149.4, 148.2, 146.5, 140.5, 131.0, 129.8, 127.4, 124.3, 119.9, 116.5, 105.5, 61.1, 56.3, 33.7, 24.0, 16.0, IR ν max (KBr, cm −1 ) 3022, 2997, 2959, 2833, 1722, 1632, 1005, 1582, 1504, 822 [ 58 ].…”

Section: Methodsmentioning

confidence: 99%

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.

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Section: Methodsmentioning

confidence: 99%

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

et al. 2018

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“…These results strongly suggest that 3 a – d and 3 f bind with Na V irreversibly, which may account for the potent inhibitory activity. We considered that the enone moiety in these derivatives might serve as a Michael acceptor for amino acid residues such as Cys, Tyr, Asp, and Glu in the binding domain, resulting in an irreversible reaction . Next, the recovery from Na V 1.5 was investigated, because the STX‐binding site in Na V 1.5 carries a cysteine residue in Domain I (corresponding to Phe 385 in Na V 1.2 or Tyr 362 in Na V 1.7), which might serve as a Michael donor (Table ).…”

Section: Resultsmentioning

confidence: 99%

“…These resultss trongly suggest that 3a-d and 3f bind with Na V irreversibly,w hich may account for the potent inhibitory activity.W ec onsidered that the enone moiety in these derivatives might serve as aM ichael acceptor for amino acid residues such as Cys, Tyr, Asp, and Glu in the binding domain, resulting in an irreversible reaction. [25,26] Next, the recovery from Na V 1.5 was investigated, because the STX-binding site in Na V 1.5c arriesacysteiner esidue in Domain I( corresponding to Phe 385 in Na V 1.2 or Tyr 362 in Na V 1.7), which might serve as aM ichael donor ( Table 1). The 293T cells expressing Na V 1.5 was perfused with 2 and 3a,a nd the recovery rates were determined as 65 and 38 %, respectively.N otably, the recovery rate from Na V 1.5w as smaller than that from Na V 1.2, irrespective of whether 2 or 3a wasu sed for perfusing the cells.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of C12‐Keto Saxitoxin Derivatives with Unusual Inhibitory Activity Against Voltage‐Gated Sodium Channels

Adachi

Yamada

Ishizuka

et al. 2020

Chemistry A European J

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An ovel series of C12-keto-type saxitoxin (STX) derivatives bearinga nu nusualn onhydrated form of the ketone at C12 has been synthesized,a nd their Na V -inhibitory activity has been evaluated in ac ell-based assay as well as whole-cell patch-clamp recording. Among these compounds, 11-benzylidene STX (3a)s howedp otent inhibitory activity againstn euroblastoma Neuro2Ai nboth cell-baseda nd electrophysiological analyses,w ithE C 50 and IC 50 valueso f8 .5 and 30.7 nm,r espectively.I nterestingly,t he compound showed potent inhibitory activity against tetrodotoxin-resistant subtype of Na V 1.5, with an IC 50 value of 94.1 nm.D erivatives 3a-d and 3f showedl ow recovery rates from Na V 1.2 subtype (ca4 5-79 %) comparedt on atural dcSTX (2), strongly suggesting an irreversible mode of interaction. We propose an interaction model for the C12-ketod erivatives with Na V in which the enonem oiety in the STX derivatives 3 worksa sM ichaela cceptorf or the carboxylateo fA sp 1717 .

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“…6 On the other hand, the intermolecular version employing a direct nucleophilic activation of a carboxylic acid has seldom been achieved barring a couple of reports. 7,8 Focusing specifically on methyl vinyl ketone as the Michael acceptor, addition of a carboxylic acid would grant access to 4-acyloxy-2-butanones and eventually 1,3-butanediols, structural motifs that find numerous applications as potential building blocks in natural product synthesis. 9 In the literature, acyloxy butanones have generally been accessed by esterification of 4-hydroxy-2-butanone using the corresponding acid chloride, 10 among other singular examples.…”

mentioning

confidence: 99%

A Nucleophilic Activation of Carboxylic Acids by Proline: Oxa-Michael Addition to Methyl Vinyl Ketone under Solvent-Free Conditions

Jha

Inani

2017

Synlett

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A serendipitous nucleophilic activation of carboxylic acids by proline helped to achieve a direct hydrocarboxylation of methyl vinyl ketone at 60 °C under solvent-free conditions. A variety of carboxylic acids were used successfully in this oxa-Michael addition, affording useful 4-acyloxy-2-butanones in moderate yields. The reactions are carried out under solvent-free conditions, and the products are isolated in high purity by a simple work-up procedure without any need for column chromatographic purification, imparting a green quotient to the protocol. A heterodimeric non-covalent interaction between the amino acid and the carboxylic acid appears to be the most plausible mechanistic interpretation for the nucleophilic activation; additionally, the possible activation of the Michael acceptor by iminium ion formation presents an interesting case of proline acting as a bifunctional catalyst.

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Reaction of α,β‐unsaturated ketones using cerium (IV) sulfate tetrahydrate in acetic acid

Cited by 6 publications

References 14 publications

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma

Synthesis of C12‐Keto Saxitoxin Derivatives with Unusual Inhibitory Activity Against Voltage‐Gated Sodium Channels

A Nucleophilic Activation of Carboxylic Acids by Proline: Oxa-Michael Addition to Methyl Vinyl Ketone under Solvent-Free Conditions

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