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ABSTRACT: Chemoselective hydrogenation of unsaturated compounds bearing an o-nitrobenzenesulfonyl (Ns)-amide moiety, affording the corresponding saturated compounds, was accomplished efficiently without loss of the nitro group by using the Pd/MS3A catalyst and a H2 balloon. Partial hydrogenation of alkynes bearing an Ns group to corresponding cis alkenes was achieved with the combination of the Pd/BN catalyst and an additive (diethylenetriamine or acetic acid).
Organic Letters 03/2013; · 5.86 Impact Factor
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ABSTRACT: Tea polyphenol "catechins", which is a major constituent of green tea extract, has received special attention for its important bioactivities. In this article, we review the recent various syntheses of catechins by classifying the mode of of flavan ring-construction. Additionally, we also take notice of the application of the modified catechins that were created to uncover the mechanism of bioactivities and discover new activities.
Current pharmaceutical design 02/2013; · 4.41 Impact Factor
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ABSTRACT: Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity.
Bioorganic & medicinal chemistry letters 12/2012; · 2.65 Impact Factor
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ABSTRACT: Asymmetric bromolactonization of prochiral cyclohexadiene derivatives with N-bromosuccimide proceeded in the presence of (DHQD)(2)PHAL as a chiral catalyst to afford the corresponding bromolactones with up to 93% ee. This reaction was also applicable to the kinetic resolution of a racemic cyclic ene-carboxylic acid, where the starting material was recovered with high enantioselectivity.
Organic Letters 11/2012; · 5.86 Impact Factor
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ABSTRACT: Under control: A stereocontrolled total synthesis of (+)-UCS1025A, a potent telomerase inhibitor, was achieved. The synthesis features an intramolecular Diels-Alder reaction, a tandem Staudinger/aza-Wittig reaction, and stereoselective construction of the hemiaminal moiety facilitated by neighboring-group participation.
Angewandte Chemie International Edition 11/2012; · 13.45 Impact Factor
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ABSTRACT: When life gives you lemons: An efficient and convergent enantioselective total synthesis of (-)-lemonomycin, which shows potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VREF), is presented. The key reaction steps are a Hosomi-Sakurai-type cyclization, a thermodynamically controlled Pictet-Spengler reaction, and a glycosidation reaction with lemonose.
Chemistry 07/2012; 18(36):11192-5. · 5.93 Impact Factor
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ABSTRACT: Enantioselective mono-fluorination of α-keto esters was achieved using a mildly basic palladium μ-hydroxo complex as catalyst. Subsequent one-pot reduction afforded optically active β-fluoro-α-hydroxy esters. These compounds were then converted into β-fluoro-α-amino esters, which are potentially useful in medicinal chemistry research.
Angewandte Chemie International Edition 03/2012; 51(19):4581-5. · 13.45 Impact Factor
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ABSTRACT: CF(3) on C sp 3: Trifluoromethylation of allylsilane derivatives was accomplished through the use of CuI and Togni's reagent (1) under mild conditions. The reaction of allylsilanes without a substituent in the 2-position gave vinylsilane derivatives, while 2-substituted allylsilanes afforded desilylated products. The utility of the products was demonstrated through their further transformation.
Angewandte Chemie International Edition 03/2012; 51(19):4577-80. · 13.45 Impact Factor
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ABSTRACT: A cobalt-phosphine complex supported on PS-PEG beads was found to react with a propargyl carbamate tag, and the tagged molecules immobilized on the beads could be released by acidic treatment through the Nicholas reaction pathway. These reactions work in aqueous media at 4 °C, so that this catch and release procedure is compatible with conditions generally used in biochemical experiments.
Organic & Biomolecular Chemistry 09/2011; 9(22):7667-70. · 3.70 Impact Factor
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ABSTRACT: Epipolythiodiketopiperazine (ETP) alkaloids are structurally characterized by the presence of diketopiperazine rings having sensitive (poly)sulfide bridges, and most of them are classified as fungal secondary metabolites. Various biological activities have been reported for members of this family, including cytotoxic, antibacterial, antimicrobial, antiviral, antitumor, antiallergic, and antimalarial activities. Notably, some of the molecules were reported to show specific inhibitory activities against certain critical enzymes. Since the supply of these compounds from natural sources is quite limited, efficient chemical syntheses of ETP alkaloids would be useful for biological studies. However, total syntheses of ETP alkaloids remain a formidable challenge in current synthetic organic chemistry because of their structural complexity. In this review article, we present an overview of synthetic approaches to the ETP alkaloids during the past 50 years, and discuss significant milestones. We also summarize the biological activities of these compounds, focusing on the molecular mechanisms.
Israel Journal of Chemistry. 04/2011; 51(3‐4):420 - 433.
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ABSTRACT: The tandem aza-Michael reaction/enantioselective protonation of α-substituted α,β-unsaturated carbonyl compounds is described in detail. The key to success is the combined use of a Brønsted basic palladium-μ-hydroxo complex and amine salts, which allows for the controlled generation of active catalyst and nucleophilic free amines. This catalytic system was applicable to various acceptors and aromatic amines, and the desired β-amino acid derivatives with a chiral center at the α position were produced in good yield with excellent enantioselectivity (up to 98% ee). For electron-deficient amines, the introduction of free amine as an additive was effective in promoting the reaction. The results of mechanistic studies, including determination of the absolute configuration of the product, are discussed.
Chemistry - An Asian Journal 02/2011; 6(2):658-68. · 4.50 Impact Factor
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Advanced Synthesis & Catalysis 10/2010; 352(16):2708 - 2732. · 6.05 Impact Factor
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ABSTRACT: Chaetocin, a natural product isolated from Chaetomium species fungi, was reported to have various biological activities, including antitumor and antifungal activities. Recently, we reported the first total synthesis of chaetocin and its derivatives. Here, we examined the cell-death-inducing activity of these compounds in human leukemia HL-60 cells. The unnatural enantiomer of chaetocin (ent-chaetocin) was more potent than chaetocin, and was found to induce apoptosis through the caspase-8/caspase-3 activation pathway.
Bioorganic & medicinal chemistry letters 09/2010; 20(17):5085-8. · 2.65 Impact Factor
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ABSTRACT: The first total synthesis of (+)-chaetocin has been accomplished in nine steps starting from known N-Cbz-N-Me-serine using radical alpha-bromination reaction of diketopiperazine 10 and Co(I)-mediated reductive dimerization reaction of 12 as key reactions. The enantiomers show comparable inhibitory activity toward histone methyltransferase (HMT) G9a, but analogues without the sulfur functionality are inactive.
Journal of the American Chemical Society 03/2010; 132(12):4078-9. · 9.91 Impact Factor
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ABSTRACT: A highly efficient, catalytic, diastereo- and enantioselective conjugate addition of alpha-ketoesters to nitroalkenes has been devised. The reaction was applicable to various substrates. Notably, the combination of endogenous and exogenous bases was effective, allowing a small amount of the catalyst (0.1-1 mol % Ni) to promote the reaction efficiently. The synthetic utility of this reaction was demonstrated in the synthesis of substituted pyrrolidine derivatives, whose stereochemistry is closely related to biologically important natural products such as kainic acid.
Journal of the American Chemical Society 03/2010; 132(12):4036-7. · 9.91 Impact Factor
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ABSTRACT: Chiral cationic Pd aqua complexes can function as acid-base catalysts, effectively activating active methylene and methine compounds to give chiral Pd enolates. It is noteworthy that such enolate formation occurs with concomitant formation of a strong protic acid. Although the reactivity of the Pd enolate itself is not sufficient for reactions with carbon-based electrophiles, its cooperative action with the protic acid to activate the electrophiles allows the desired C-C bond-forming reactions to proceed smoothly in a highly enantioselective manner. Based on this mechanistic feature, reactions with acetals have been developed; these are difficult to achieve using conventional basic enolate chemistry.
Chemical Communications 10/2009; · 6.17 Impact Factor
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ABSTRACT: This paper describes catalytic asymmetric Mannich-type reactions of beta-ketoesters and malonates using chiral palladium complexes. Although readily enolizable, carbonyl compounds are attractive substrates, the use of such compounds as nucleophiles in Mannich-type reactions has not been extensively investigated. In the presence of chiral Pd aqua complexes (2.5 mol %), beta-ketoesters reacted with various N-Boc imines (Boc=tert-butoxycarbonyl) to afford the desired beta-aminocarbonyl compounds in good yield with high to excellent stereoselectivity (up to 96:4 d.r., 95-99 % ee in most cases). In these reactions, construction of highly crowded vicinal quaternary and tertiary carbon centers was achieved in one step. A chiral Pd enolate is considered to be the key intermediate. To elucidate the stereoselectivity observed in the reaction, possible transition-state models are discussed, taking into account steric and stereoelectronic effects. Furthermore, this catalytic system was applied to the Mannich-type reaction of malonates with N-Boc imine as well as one-pot classical aminomethylation of beta-ketoesters using benzylamine salt and formalin. The reactions proceeded smoothly, and the corresponding Mannich products were obtained in high yield with moderate to good enantioselectivity.
Chemistry - An Asian Journal 08/2008; 3(8-9):1443-55. · 4.50 Impact Factor
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ABSTRACT: Detailed mechanistic studies on our recently reported asymmetric addition reactions of malonates to dihydroisoquinolines (DHIQs) catalyzed by chiral Pd(II) complexes were carried out. It was found that an N,O-acetal was generated in situ by the reaction of DHIQ with (Boc)2O, and cooperative action of the Pd(II) complex as an acid-base catalyst allowed the formation of a chiral Pd enolate and a reactive iminium ion via alpha-fragmentation. The iminium ion was also accessible via oxidation with DDQ as an oxidant, and a catalytic asymmetric oxidative Mannich-type reaction was achieved with tetrahydroisoquinolines (THIQs) as starting materials. This oxidation protocol was applicable to N-acryloyl-protected THIQs, allowing the efficient synthesis of optically active tetrahydrobenzo[a]quinolizidine derivatives via intramolecular Michael reaction.
The Journal of Organic Chemistry 07/2008; 73(15):5859-71. · 4.45 Impact Factor
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Angewandte Chemie International Edition 02/2008; 47(22):4196-9. · 13.45 Impact Factor
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ABSTRACT: We describe herein the catalytic asymmetric conjugate reduction of a,b-unsaturated carbonyl compounds using a novel cationic Pd– i Pr-DUPHOS complex. In this reaction, EtOH worked well as a solvent and a reducing agent, and the reaction was completed within several hours in most cases to afford the reduced compounds almost quantitatively with modest to good enantioselectivity (up to 72% ee). It was found that the Pd– i Pr-DUPHOS complex was more reactive than the previously reported Pd–BINAP complex when molecular sieves 4A was added as an additive. Based on an X-ray structural analysis of [Pd{(S,S)-i Pr-duphos}](OTf) 2 complex, a working hypothesis of the reaction mechanism is also described.
11/2007;
