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ABSTRACT: Gold-catalyzed intermolecular addition of hydroxybenzotriazole derivatives to alkynes at room temperature, gives vinyl ethers 3 in high yields and with excellent regioselectivity. Unlike many other vinyl ethers, 3 can easily be purified by regular silica-gel chromatography. On heating, 3,3-sigmatropic rearrangement of 3 gives access to highly functionalized benzotriazoles. This two-step sequence represents an efficient oxygen transfer protocol which incorporates a nucleophilic oxygen atom into an alkyne group. Reaction of 3 with an electrophilic fluorinating reagent (Selectfluor) gives a fluorinated ketone regioselectively and in high yield.
Organic Letters 02/2013; · 5.86 Impact Factor
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ABSTRACT: Recently, our group reported the discovery of three new withanolides, physangulidines A-C, from Physalis angulata. In this study, the biological effects of physangulidine A (1), which was the most active and abundant of the three new constituents, are described. It was found that 1 significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1 induces cell cycle arrest in the G(2)/M phase and causes defective mitosis. It was determined also that 1 produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of 1 may contribute significantly to the biological activities and potential medicinal properties of its plant of origin.
Journal of Natural Products 12/2012; · 3.13 Impact Factor
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ABSTRACT: A copper-catalyzed tandem-cyclization-triggered addi-tion strategy that relies on electrophilic enamine activation has been used to synthesize various cyclic -aminophosphonate derivatives in good to excellent yields. Both five-and six-membered rings can be generated under mild conditions with high regioselectivity. A mechanism based on copper-catalyzed enamine activation is pro-posed.
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ABSTRACT: Allenyl carbinol ester 3 isomerizes to an E,Z mixture of the corresponding diene 2 in the presence of gold catalyst 4, but the resulting mixture yields monofluoroalkyl α,β-unsaturated ketone 1 with exclusive E selectivity and in high yields after reaction with Selectfluor.
The Journal of Organic Chemistry 08/2012; 77(17):7725-9. · 4.45 Impact Factor
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ABSTRACT: Bioassay-directed fractionation of the whole plant of Physalis angulata L. afforded three new antiproliferative withanolides with an unusual carbon framework: physangulidines A (1), B (2), and C (3). Structures of the three isomeric withanolides were determined by a combination of HRMS, NMR spectroscopic, and X-ray crystallographic methods. Each has shown significant antiproliferative activity against DU145 prostate cancer cells. Physangulidine A (1) was further tested against a wide range of additional cancer cell lines and found to exhibit significant antiproliferative activity.
Organic Letters 03/2012; 14(5):1230-3. · 5.86 Impact Factor
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ABSTRACT: Gold catalysis is considered one of the most important breakthroughs in organic synthesis during the past decade, but a rational understanding of ligand effects in gold catalysis is lacking. Most gold-catalyzed reactions go through three major stages: (i) electronic activation of alkyne (or allene) to generate a vinyl gold intermediate; (ii) protodeauration to generate the product and regenerate the cationic gold catalyst; (iii) decay of the active gold catalyst. Our research provides a clearer understanding of how ligands influence each of the three stages in the gold catalytic cycle. What is even more important, by not focusing on a particular gold-catalyzed reaction, we have been able to categorize most gold-catalyzed reactions and propose a ligand design protocol for each category of gold-catalyzed reactions.
Journal of the American Chemical Society 02/2012; 134(12):5697-705. · 9.91 Impact Factor
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ABSTRACT: Homogeneous gold catalysis has been one of the most active research fields in organic chemistry for more than a decade, and it has been also among the most efficient methodologies for forming carbon-carbon or carbon-heteroatom bonds. Recently, a number of organogold intermediates were isolated from stoichiometric reactions, which helps to better understand the mechanisms. Meanwhile, the reactivity of organogold compounds has been attracting the attention of organic chemists in the field. This tutorial review collects the most recent advances in the isolation and reactivity of organogold compounds that may help to open new directions in homogenous gold catalysis.
Chemical Society Reviews 01/2012; 41(8):3129-39. · 28.76 Impact Factor
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ABSTRACT: The gold-catalyzed intramolecular oxygen-transfer reactions of 2-alkynyl-1,5-diketones or 2-alkynyl-5-ketoesters-obtained from tetra-n-butylammonium fluoride mediated Michael addition of activated allenes to electron-deficient olefins-furnished cyclopentenyl ketones under very mild conditions. These reactions proceeded much easier and faster than similar reactions reported in literature, and the corresponding products were obtained in very good yields. Mechanistic investigations on the cycloisomerization were carried out by means of both (18) O isotopic experiments and quantum chemical calculations. The results from both, the designed isotopic experiments and theoretical calculations, satisfactorily supported the novel proposed intramolecular [4+2] cycloaddition of a gold-containing furanium intermediate to a carbonyl group, instead of the previous well-accepted [2+2] pathway.
Chemistry 08/2011; 17(38):10690-9. · 5.93 Impact Factor
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ABSTRACT: Using a readily available secondary aminoalkyne as starting material, a powerful strategy was discovered to prepare precursors of biologically important unnatural cyclic aminoacids and fluorinated N-heterocycles with important ring sizes (e.g., 5-7) in a one-pot reaction using two nucleophilic additions in a tandem fashion.
Organic Letters 07/2011; 13(13):3450-3. · 5.86 Impact Factor
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ABSTRACT: An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes.
Planta Medica 04/2011; 77(14):1597-9. · 2.15 Impact Factor
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ABSTRACT: During the last decade, gold-catalyzed reactions have become a tour de force in organic synthesis. Recently, the gold-, Brønsted acid- or Lewis acid-catalyzed oxygen transfer from carbonyl to carbon-carbon triple bond, the so-called alkyne-carbonyl metathesis, has attracted much attention because this atom economical transformation generates α,β-unsaturated carbonyl derivatives which are of great interest in synthetic organic chemistry. This mini-review focuses on the most recent achievements on gold-catalyzed oxygen transfer reactions of tethered alkynones, diynes or alkynyl epoxides to cyclic enones. The corresponding mechanisms for the transformations are also discussed.
Beilstein Journal of Organic Chemistry 01/2011; 7:606-14. · 2.52 Impact Factor
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Annalen der Chemie und Pharmacie 10/2010; 2010(35):6855 - 6862. · 3.10 Impact Factor
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ABSTRACT: Gold-catalyzed reactions of 2-(ynol)aryl aldehydes were investigated. Benzochromanes were obtained from the reaction when AuCl(3) was employed as the catalyst, whereas benzobicyclo[n.3.1]acetals were produced when triazole-gold was employed as the catalyst. Plausible mechanisms are discussed.
Organic Letters 10/2010; 12(20):4640-3. · 5.86 Impact Factor
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Angewandte Chemie International Edition 10/2010; 49(48):9132-5. · 13.45 Impact Factor
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Angewandte Chemie International Edition 09/2010; 49(40):7247-52. · 13.45 Impact Factor
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José C Aponte,
Abraham J Vaisberg,
Denis Castillo,
German Gonzalez,
Yannick Estevez,
Jorge Arevalo,
Miguel Quiliano,
Mirko Zimic,
Manuela Verástegui,
Edith Málaga,
Robert H Gilman,
Juan M Bustamante,
Rick L Tarleton,
Yuehong Wang,
Scott G Franzblau,
Guido F Pauli,
Michel Sauvain, Gerald B Hammond
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ABSTRACT: The synthesis of 2-(5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)hydrazone-derivatives (BTPs) and their in vitro evaluation against Trypanosoma cruzi trypomastigotes, Mycobacterium tuberculosis, Leishmania amazonensis axenic amastigotes, and six human cancer cell lines is described. The in vivo activity of the most active and least toxic compounds against T. cruzi and L. amazonensis was also studied. BTPs constitute a new family of drug leads with potential activity against infectious diseases. Due to their drug-like properties, this series of compounds can potentially serve as templates for future drug-optimization and drug-development efforts for use as therapeutic agents in developing countries.
Bioorganic & medicinal chemistry 03/2010; 18(8):2880-6. · 2.82 Impact Factor
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ABSTRACT: An aminoalkyne (terminal or internal) and a terminal alkyne furnish functionalized five-, six-, and seven-membered N-heterocycles in excellent yields via a Cu(I)-catalyzed, one-pot, tandem hydroamination/alkynylation process.
Journal of the American Chemical Society 01/2010; 132(3):916-7. · 9.91 Impact Factor
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ABSTRACT: gem -Difluoro-1,7-enyne amides are suitable building blocks for the synthesis of difluorodihydropyridinones via a ring-closing metathesis reaction, and of 4,4-difluoro-3-oxoisoquinolines through a ring-closing metathesis–enyne metathesis tandem reaction. These products, in turn, undergo a Diels–Alder reaction to yield heterotricyclic systems in moderate to good yields.
Beilstein Journal of Organic Chemistry. 01/2010;
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ABSTRACT: The in vitro screening of 43 polysubstituted chalcones against Leishmania amazonensis axenic amastigotes, led to the evaluation of 9 of them in a macrophage-infected model with the two other most infectious Leishmania species prevalent in Peru (L. braziliensis and L. peruviana). The five most active and selective chalcones were studied in vivo, resulting on the identification of two chalcones with high reduction parasite burden percentages.
Bioorganic & medicinal chemistry letters 11/2009; 20(1):100-3. · 2.65 Impact Factor
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ABSTRACT: A highly efficient gold(I) chloride catalyzed cycloisomerization of 2-alkynyl-1,5-diol (1) to dioxabicyclo[4.2.1] ketal (2) and its further transformation to tetrahydropyran (3) are reported. The diol is readily obtained by the reduction of 2-alkynyl-substituted glutarates, isolated from the Michael addition of allenoates to methyl acrylate. These reactions proceeded smoothly under very mild conditions. A plausible mechanism for the formation of the said tetrahydropyran from the corresponding ketal is proposed.
Organic Letters 10/2009; 11(21):5090-2. · 5.86 Impact Factor
