西田 篤司

Highly regio- and stereoselective homodimerizative [2 + 2] cycloaddition of allenamides under nickel catalysis was developed. Xantphos is an essential ligand to give “tail to tail” products and DFT studies revealed that oxidative addition between a nickel(0) complex and two distal C[dbnd]C bonds of the allenamides would be a key process. Sequential formation of the metallacycle intermediate would proceed in both a regio- and stereoselective manner to give the corresponding cyclobutane as a single isomer.

<jats:p>Vinylallenes have been recognized as versatile C2 and C4 components for nickel-catalyzed intramolecular [4+2] and [2+2] cycloadditions. The former reaction was promoted by a Ni(0) complex (up to quantitative yield),...</jats:p>

Targeting cell‑cycle regulation to hinder cancer cell proliferation is a promising anticancer strategy. The present study investigated the effects of a novel sulfonamide, CCL113, on cell cycle progression in cancer cell lines (HeLa and HepG2), a noncancerous cell line (Vero) and a normal human fibroblast cell line (TIG‑1‑20). The present results showed that treatment with CCL113 significantly decreased the viability of the cancer cells. FACS analyses showed that CCL113 treatment increased the proportion of cancerous and noncancerous cells in the G2/M phase. Analyses of cell cycle regulatory proteins showed that CCL113 treatment inhibited the activity of CDK1 in HeLa cells, possibly due to the decrease in the level of Cdc25B/C proteins and arrest in the M phase. Using time‑lapse imaging‑assisted analyses of HeLa and Vero cells expressing fluorescent ubiquitination‑based cell cycle indicator (FUCCI), it was observed that CCL113 treatment led to a prolonged G2 phase at the G2/M checkpoint and arrest in the M phase in both cell lines. This possibly activated the DNA damage response in noncancerous cells, while inducing mitotic arrest leading to apoptosis in the cancer cells. The results of molecular docking studies suggested that CCL113 might have the potential to bind to the taxol‑binding site on β‑tubulin. In conclusion, CCL113 holds potential as a reliable anticancer drug due to its ability to induce mitotic arrest followed by apoptosis of cancer cells and to activate the DNA damage response in noncancerous cells, thereby facilitating exit from the cell cycle.

A one-step synthesis of enones from olefins is described. The reaction was performed under visible-light irradiation in the presence of molecular oxygen and a photocatalyst. The reaction proceeded with various types of trisubstituted olefins to give enones in good yields with high regioselectivity. In particular, oxygen- and nitrogen-containing functional groups, heteroaromatic rings, and cyclopropanes were tolerated. Mechanistic studies and previous reports indicated that the active oxygen species generated in the reaction system is singlet oxygen.

Copyright © 2020 American Chemical Society. In vitro assessment of lipid intermembrane transfer activity by cellular proteins typically involves measurement of either radiolabeled or fluorescently labeled lipid trafficking between vesicle model membranes. Use of bilayer vesicles in lipid transfer assays usually comes with inherent challenges because of complexities associated with the preparation of vesicles and their rather short "shelf life". Such issues necessitate the laborious task of fresh vesicle preparation to achieve lipid transfer assays of high quality, precision, and reproducibility. To overcome these limitations, we have assessed model membrane generation by bicelle dilution for monitoring the transfer rates and specificity of various BODIPY-labeled sphingolipids by different glycolipid transfer protein (GLTP) superfamily members using a sensitive fluorescence resonance energy transfer approach. Robust, protein-selective sphingolipid transfer is observed using donor and acceptor model membranes generated by dilution of 0.5 q-value mixtures. The sphingolipid transfer rates are comparable to those observed between small bilayer vesicles produced by sonication or ethanol injection. Among the notable advantages of using bicelle-generated model membranes are (i) easy and straightforward preparation by means that avoid lipid fluorophore degradation and (ii) long "shelf life" after production (≥6 days) and resilience to freeze-thaw storage. The bicelle-dilution-based assay is sufficiently robust, sensitive, and stable for application, not only to purified LTPs but also for LTP activity detection in crude cytosolic fractions of cell homogenates.

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Lanthanide triflates and a series of hexadentate chiral ligand complexes were synthesized. X-ray-quality crystals were obtained from mixtures of the lanthanide complexes, which were helical in shape. The complexes showed Lewis acidity and catalyzed the enantioselective Diels–Alder reaction of electron-rich siloxydienes. The complexes were stable enough to be stored at ambient temperature on a laboratory bench and retained their Lewis acidity even after a month.

Synthesis of cyano-functionalized nitrogen heterocycles under palladium, nickel, and cobalt catalysis is described. These transformations include the activation of C-C multiple bonds to give the functionalized pyrrolidines and their related compounds. The palladium-catalyzed reactions promote nucleophilic cyanation to non-activated terminal alkynes. Nickel catalysis enables to install H and CN functionalities into allenes with regio- and stereoselective manner. In the case of cobalt-catalyzed hydrocyanation, hydroacylation and hydroarylation, simple olefins as well as enamines are suitable substrates to construct highly functionalized hetero- and carbocycles. The applications of the above methodologies for the synthesis of alkaloids and related compounds are also described.

© 2019 Elsevier Ltd A mild, general and efficient hydrocyanation and hydroarylation of enamines catalyzed by Co(salen) complexes are described. Both reactions include regioselective C[sbnd]H bond formation of enamines, and the corresponding products are obtained in high yield. Hydroarylation critically discriminates the benzyl and benzoyl aromatic rings on nitrogen in cyclization step, and the corresponding isoindolinones including quaternary carbons are exclusively given.

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A Ni-catalyzed [2+2+2] cycloaddition reaction between allene-ynes and various mono-, di- and tri-substituted allenes is described. This protocol effectively differentiates allenyl π components and shows broad substrate generality to give highly functionalized carbocycles. A DFT study played a key role in revealing a detailed reaction mechanism that controls site-, regio- and stereoselectivity, which are thought to originate in the substituent effect on π-bonds in the early transition state. (Figure presented.).

© 2019 Elsevier Ltd A nickel-catalyzed [2 + 2] cycloaddition of bisallenes has been described. Simple bisallenes are employed for the formation of “head to head” cycloadducts in the presence of Ni(0) with xantphos. The dienyl moiety in a product were applicable for various [4 + 2] cycloaddition reactions. Allene-allenamides under Ni-xantphos system gave the tricyclic compounds through sequential [2 + 2]–[4 + 2] cycloaddition reaction in highly stereoselective manner.

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Diels-Alder reaction is one of the most well-known named reactions in organic chemistry. It involves a diene substrate and a dienophile substrate. Among dienes, siloxydiene is a reactive substrate that is often used in Diels-Alder reaction. In general, Diels-Alder reaction is promoted by an acidic reagent. In many cases, the stereoselectivity of the reaction is also controlled by acids. However, siloxydienes are labile under acidic conditions. Thus, it should be difficult to develop a reaction using siloxydiene as a substrate. Nevertheless, siloxydienes are still used in synthetic organic chemistry, and most reactions are performed under thermal activation conditions. In this minireview, we summarize the reported examples of catalytic and enantioselective Diels-Alder reactions of siloxydienes based on the structure of the diene. We present the activation methods used, the existing problems, and a clue for the further development of this annulation chemistry.

© 2019 Nickel-catalyzed regioselective hydrocyanation of terminal alkynes is described. A tosylamide functionality at the propargyl position was the most suitable group for controlling the regiochemistry for C–CN bond formation as well as rate enhancement. A gram-scale synthesis was achieved by minimizing the catalyst loading to 2 mol%. The major HCN adduct could be transformed to the corresponding indoline through construction of a benzylic quaternary carbon under iron catalysis.

© 2018 Regio- and stereoselective sulfonylation of allenes under Cu catalysis is described. Allenyl sp carbons exclusively react with TsCN to give the corresponding alkenyl sulfones. The reaction is initiated by addition of tosyl radical to form benzyl radical intermediates, which determines the reaction pathway. The structure of the products is highly dependent on the substituents on allenes.

© 2019 The Royal Society of Chemistry. Fungi, including mushrooms and mycelia, are a rich source for natural products with medicinal properties. In some cases, they can lead to opportunistic infections in humans and other mammals. In 1994, the first case of bronchopulmonary mycosis caused by the Schizophyllum commune fungus was described. Culture of the isolated specimen led to the extraction of an alkaloid compound, schizocommunin, which was more recently synthesised for biological characterization. Herein we describe schizocommunin and one of its analogues as cytotoxic against human hepatoma cells at low micromolar concentrations. Schizocommunin is shown to be a potent activator of the aryl hydrocarbon receptor (AhR) gene battery, more specifically increasing expression of the CYP1A1, CYP1B1 and UGT1A genes in human liver and lung cells. A luciferase reporter assay further confirms induction of transcription by these compounds at the xenobiotic response element. This study improves our understanding of the interaction between this fungal metabolite and xenobiotic detoxifying mechanisms in the body, and points to schizocommunin as a putative mediator of the allergic response and a useful molecule for the study of the AhR pathway.

© 2019 The Royal Society of Chemistry. An efficient synthesis of carbo-and heterocycles using CC, CO and CN bonds under cobalt catalysis is described. The substituents on olefins are key for controlling the regio-and chemoselectivity in the initial hydrogen atom transfer step and quaternary carbons are efficiently constructed under mild conditions. Cyclopropane cleavage and tandem cyclization give highly functionalized bicyclic skeletons in a single operation.

© 2018 Elsevier Ltd A new ceramide analog, 1, containing two fluorescent dyes, NBD in the N-acyl part and KFL5 in the alkyl part, was synthesized. The fluorescence from both NBD and KFL5 was detected in living cells in a time-dependent manner. A multi-wavelength fluorescence detector was used to detect ceramide metabolites including sphingosine, sphingosine-1-phosphate, glucosylceramide, and sphingomyelin, which are connected to the fluorescent dyes, simultaneously in a single TLC plate.

© 2018 American Chemical Society. A new approach for the synthesis of highly functionalized tetrahydrocyclohepta[b]indoles through [5 + 2] cycloaddition was developed. Two carbon-carbon bonds were formed by the simple addition of an indium catalyst, which acted as both a δ-Lewis acid and σ-Lewis acid to activate the alkyne and unsaturated ester, respectively. The reaction could be applied to various substrates and proceeded regio- and diastereoselectively in all cases.

© 2018 Elsevier Ltd We developed an enantioselective carbonyl-ene-type cyclization using 2-substituted vinylsilane as a nucleophilic ene moiety catalyzed by a chiral copper-BOX complex. This reaction is the first example of enantioselective carbonyl-ene cyclization using a 1,2-disubstituted olefin. This methodology gave chiral indenols with a tetrasubstituted carbon.

© 2018 Elsevier Ltd This article describes the formal synthesis of quebrachamine based on regio- and stereoselective hydrocyanation of 1,3-disubstituted allenes. Allenyl C–C double bonds are effectively discriminated through Ni-catalyzed hydrocyanation and a CN group is utilized as a synthon of piperidine ring. Several steps from HCN adduct afforded known intermediates to quebrachamine.

© 2018 The Pharmaceutical Society of Japan. Total syntheses of carbazomycins A and B were demonstrated using a ytterbium-catalyzed Diels-Alder reaction with (silyloxyvinyl)indole as a diene. The densely substituted benzene ring of the target compound was successfully constructed by functionalization of a hydrocarbazolone intermediate and subsequent aromatization using N-bromosuccinimide.

© 2017 Elsevier Ltd The natural hydrocarbazolone alkaloid (1R,2R,3R)-3-hydroxy-1,2-dimethyl-1,2,3,9-tetrahydro-4H-carbazol-4-one has been synthesized in a catalytic and enantioselective manner. A key hydrocarbazole derivative was constructed by the holmium-catalyzed Diels-Alder reaction of (silyloxyvinyl)indole as the diene. Total synthesis of the natural product clarified the ambiguity in the spectroscopic data reported for natural products.

© The Royal Society of Chemistry. The transfer of axial chirality of allenes is beginning to be exploited as a powerful method for creating central chirality, particularly through the use of transition metal catalysis. In this communication, the transfer of axial chirality of chiral allenes via nickel-catalysed hydrocyanation is achieved through both regio- and face-selective hydronickelation as well as regioselective reductive elimination. This protocol was applied to 12 substrates and gave chiral carbonitriles with up to 97% ee. Further application to hydrocyanative cyclization using a chiral allene-yne is also presented, along with a discussion of the corresponding mechanism of racemization.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim A nickel-catalyzed hydrocyanation triggered by hydronickelation of the carbon-carbon double bonds of allenes followed by cyclopropane cleavage is described. The observed regio- and stereochemistries in the products are strongly influenced by the initial hydronickelation step, and allenyl- and methylenecyclopropanes reacted smoothly to promote the cleavage of cyclopropane. In contrast, this cleavage was not observed with vinylidenecyclopropanes, because the initial hydronickelation does not give a suitable intermediate for cleavage of the cyclopropanes. (Figure presented.).

© 2017 The Japan Institute of Heterocyclic Chemistry Received. The enantioselective Diels-Alder reaction of silyloxydiene that incorporates a pyrrolidine ring was studied. This reaction was catalyzed by a chiral holmium complex and gave multi-substituted chiral hydroindoles that contained a silyl enol ether, which is a key functional group for further transformations. We demonstrate here the synthesis of chiral pyrroloacridine, dibenzodiazocine, and pyrrolocarbazole skeletons.

© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies. Enantioselective total syntheses and determination of the absolute stereochemistry of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and following enantioselective deprotonation, lactone formation, vinylation, allylic amination, and ring-closing metathesis, gave the above alkaloids in optically active form.

© 2016 The Pharmaceutical Society of Japan. We have developed a new method for synthesizing chiral isotwistane and homoisotwistane skeletons as well as aminocyclitols in a highly stereoselective manner. These results were achieved through the use of a common intermediate, which was derived from the ytterbium-catalyzed asymmetric Diels-Alder reaction of Danishefsky diene.

© 2015 American Chemical Society. A Ni(NTf2)2 and tetradentate bisimino-bisquinoline ligand complex catalyzed the enantioselective Nazarov cyclization of heteroaryl vinyl ketones. An X-ray-quality crystal was obtained from a mixture of the Ni complex and the substrate, which was the dinuclear chiral Ni complex. From information regarding the structure of the complex, the substrate was distorted to form a helical shape, and the carbon atoms involved in bond formation were close to each other. In addition, mechanistic studies revealed that the configuration of the olefin moiety was isomerized before bond formation.

© 2015 American Chemical Society. The catalytic and enantioselective total synthesis of (-)-minovincine has been accomplished. The key highly substituted hydrocarbazole derivative was obtained by an asymmetric Diels-Alder reaction of siloxyvinylindole catalyzed by 0.5 mol % of a chiral holmium complex. The Diels-Alder adduct was converted to a tetracyclic intermediate in a one-pot procedure. No waste stereoisomers were produced throughout the entire total synthesis.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. The Golgi complex plays a prominent role in the modification and sorting of lipids and proteins, and is a highly dynamic organelle that is dispersed and rearranged before and after mitosis. Several reagents including 4-nitrobenzo-2-oxa-1,3-diazole-labeled C6-ceramide (NBD-C6-ceramide, a ceramide having an NBD-bound C6-N-acyl chain) and Golgi-specific proteins that emit fluorescence are used as Golgi markers. In the present study, we synthesized a new ceramide analog, acetyl-C16-ceramide-NBD (a ceramide having an acetylated C-1 hydroxyl group, C16-N-acyl chain, and NBD-bound C15-sphingosine), and showed that it preferentially accumulated in the Golgi complex without cytotoxicity for over 24 h. Pathways for cellular uptake and interorganelle trafficking of acetyl-C16-ceramide-NBD were investigated. Acetyl-C16-ceramide-NBD was transported to the Golgi complex via ceramide transport proteins. In contrast to NBD-C6-ceramide, acetyl-C16-ceramide-NBD was resistant to ceramide metabolic enzymes such as sphingomyelin synthase and glucosylceramide synthase. Because of its weaker cytotoxicity and resistance to ceramide metabolic enzymes, the localization of the Golgi complex could be observed in acetyl-C16-ceramide-NBD-labeled cells before and after mitosis.

© The Royal Society of Chemistry 2015. Regio- and stereoselective hydrocyanation under nickel catalysis is described. This report shows that allenyl C-C double bonds are discriminated and converted to the corresponding carbonitriles as a single product. The key functionalities for achieving high regio- and stereocontrol are aryl and cyclopropyl groups in the substrates. This journal is

© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. A total synthesis of the Kopsia tenuis alkaloid (-)-lundurine B has been achieved. A quaternary chiral carbon has been created by an asymmetric deprotonation using a symmetric spiro cyclohexanone intermediate with a chiral lithium amide. The hexacyclic skeleton was sequentially constructed through metal-mediated reactions. The absolute stereochemistry of intermediate 5 has been unambiguously established by X-ray crystallographic analysis. This is the first description of the absolute stereochemistry of Kopsia tenuis alkaloids based on chemical synthesis.

© 2015 The Japan Institute of Heterocyclic Chemistry. A chiral decahydroisoquinoline was constructed using our asymmetric Diels-Alder reaction catalyzed by a chiral Yb (ytterbium) complex as a key step. The decahydroisoquinoline is a synthetic intermediate of the anti-obesity drug candidate AMG 076 (Amgen).

© 2014 Elsevier Ltd. All rights reserved. The catalytic Diels-Alder reaction of siloxyvinylindole and cyclic Z-olefin derived from pyroglutamic acid gave optically active substituted hydrocarbazoles. The exo/endo selectivity of this reaction could be controlled by using an appropriate Lewis acid. Scandium triflate gave high exo-selectivity and copper triflate gave moderate endo-selectivity. Subsequent stereoselective alkylation of the cycloadduct led to the synthesis of highly substituted hydrocarbazoles with five continuous chiral centers including a quaternary carbon.

A total synthesis of (±)-lundurines A and B is described. These natural products have a unique hexacyclic skeleton which includes a cyclopropane-fused indoline. A stereospecific construction of the pentasubstituted cyclopropane core was achieved, by radical cyclization using SmI2, with perfect stereoselectivity. Cyclizations to give seven- and five-membered heterocycles, under palladium and ruthenium catalysis, respectively, accomplished the total syntheses. The late-stage construction of the F ring by ring-closing metathesis enabled access to the title compounds from a spiroindoline intermediate which is a common structure of other kopsia alkaloids. To the core: The total synthesis of (±)-lundurines A and B is described. One of the key reactions is a SmI2-mediated cyclopropanation, which delivered the core structure with perfect stereocontrol of the quaternary carbon centers. Palladium- and ruthenium-catalyzed cyclizations were also effective for constructing seven- and five-membered heterocycles, respectively, to complete the total syntheses. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A total synthesis of (±)-lundurine B was accomplished. A combination of stereoselective intramolecular cyclopropane formation and aryl amination furnished cyclopropane-fused indoline stereoselectively. Ring-closing metathesis (RCM) of siloxy diene and intramolecular aminoacetal formation followed by bridgehead vinylation of an anti-Bredt iminium cation led to the construction of six- and seven-membered rings with a quaternary carbon center. After the formation of dihydropyrrole by RCM, the Boc-protecting group of indoline was converted into the corresponding methyl carbamate via silyl carbamate to complete the total synthesis of (±)-lundurine B. The characteristic rearrangement of the cyclopropane-fused indoline skeleton is also described. © 2014 American Chemical Society.

A [2+2] cycloaddition reaction of allene-ynes under thermal conditions with/without a metal complex is described. A key feature of this reaction is that a 2-benzothiazolylphenyl group bearing a C-C triple bonds remarkably promotes the reaction to give the corresponding cyclobutenes with or without metal catalysts. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A proposed structure for schizocommunin (Z)-1hydroxy and its geometric isomer (E)-1hydroxy, which exist in a keto form, has been synthesized. However, the spectroscopic data of (Z)-1keto and (E)-1keto were not consistent with those reported for natural schizocommunin. After reinvestigating the spectral data for natural schizocommunin, we synthesized the quinazolinone derivative (Z)-2 as a revised structure for schizocommunin. All of the spectral data of (Z)-2 were completely identical to those reported for natural schizocommunin. (Z)-2 showed moderate antiproliferative activity. © 2013 The American Chemical Society and American Society of Pharmacognosy.

The carbocyanative cyclization of allene-ynes and bis-allenes under nickel catalysis is described. The key steps are the regioselective hydronickelation of allenes and subsequent cyclization via carbometalation. The former step determines the reaction pathway, and the latter controls the stereochemistry of substituted olefins. The products are useful carbo- and heterocycles that include a cyano group, functionalized double bonds, and quaternary carbons. © 2013 American Chemical Society.

The catalytic and asymmetric cycloaddition between 3-[1-(silyloxy)vinyl] indoles and electron-deficient olefins gave substituted hydrocarbazoles in up to 99% yield and 94% ee. This reaction was catalyzed by a novel chiral holmium(III) complex. Alkylation of the cycloadduct gave a tricyclic compound with four continuous chiral centers, one of which was a quaternary carbon. © 2013 American Chemical Society.

Packed with functionality: The key step in the title reactions with acetone cyanohydrin is a regioselective hydronickelation of allenes. Subsequent carbometalation of the alkyne followed by reductive elimination gave cyano-functionalized tetrasubstituted alkenes in a regio- and stereoselective manner (see scheme; EWG=electron-withdrawing group, Ts=p-toluenesulfonyl). Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti carbocyanative cyclization using 1,6-enynes under nickel catalysis is described. This reaction is triggered by hydronickelation to alkenes followed by carbometalation. Steric repulsion caused by the bulky substituents on alkynes promotes isomerization of the carbon-carbon double bond geometry in an organonickel intermediate to introduce both alkyl and cyano groups in an anti fashion. © 2013 American Chemical Society.

A nickel-catalyzed three-component coupling reaction through cyanation of a carbon-carbon triple bond is described. A nickel(0) complex effectively catalyzes a sequential coupling reaction between allenes, alkynes and hydrogen cyanide from acetone cyanohydrin in a highly regio-and stereoselective fashion. The trigger for this reaction is hydronickelation to allenes. The initial hydride attack predominantly occurs at the central carbon of the allene to give a p-allylnickel(II) species. Subsequent syncarbometalation connects a β-carbon of alkynoates and a less-hindered carbon of the allylnickel(II) species, and the corresponding cyanoalkenes are obtained as a single stereoisomer without any another organometallic reagents as a coupling partner. © 2013 Wiley-VCH Verlag GmbH&Co. KGaA, Weinheim.

Ceramide-1-phosphate (C1P) has been shown to bind with C2 domain in group IVA cytosolic phospholipase A2 (cPLA2α, PLA2G4A) and activate the enzyme activity directly. In cells, C1P causes translocation of cPLA2α to perinuclear regions including the Golgi complex by interacting with C2 domain in the enzyme, and then cPLA2α releases arachidonic acid from substrate phospholipids in the regions. In this study, we synthesized new di-ethyl (DE) phosphate ester analogs of C1P with N-acyl chains of different lengths, and examined their effects on cPLA 2α. A DE-C1P analog with a C2-N-acyl chain (C2-DE-C1P), but not DE-C1P analogs with longer N-acyl chain, such as C6- and C16-DE-C1P, inhibited release of arachidonic acid via cPLA2α activation in CHO-W11A cells expressing platelet-activating factor (PAF) receptors without changing secretory phospholipase A2-induced release. Treatment with C2-DE-C1P did not modify phosphorylation of extracellular signal-regulated kinase 1/2 and cPLA2α and increase of intracellular Ca2+ level induced by PAF, but inhibited Ca2+- and PAF-induced accumulation of cPLA2α in the Golgi complex. Phosphatidylcholine vesicles containing C2-DE-C1P reduced cPLA2α activity in vitro. C2-DE-C1P disturbed the binding of the enzyme to glycerophospholipids in the lipid-protein overlay assay, and the reagent alone did not bind to the enzyme. Interestingly, C2-DE-C1P inhibited neither Ca2+- and PAF-induced accumulation of C2 domain of cPLA2α in the Golgi complex nor binding of cPLA2α to C16-C1P. These results suggest that C2-DE-C1P appeared to inhibit cPLA2α, probably by interaction with a site in the catalytic domain of the enzyme, not with the site in C2 domain responsible for native C1P. © 2012 Elsevier B.V. All rights reserved.