3958-83-6Relevant academic research and scientific papers
Rh-Catalyzed [2 + 2 + 2] Cycloadditions with Benzoquinones: De Novo Access to Naphthoquinones for Lignan and Type II Polyketide Synthesis
Wood, James M.,Da Silva, Eufranio N.,Bower, John F.
supporting information, p. 265 - 269 (2020/01/02)
The first examples of Rh-catalyzed [2 + 2 + 2] cycloadditions between diynes and benzoquinones are described. The method enables de novo and step-economical access to challenging naphthoquinones that are of relevance to lignan and type II polyketide synthesis. The value of the chemistry is demonstrated by a short total synthesis of justicidone.
Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2?+?2?+?2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi
Wood, James M.,Satam, Nishikant S.,Almeida, Renata G.,Cristani, Vinicius S.,de Lima, Dênis P.,Dantas-Pereira, Luiza,Salom?o, Kelly,Menna-Barreto, Rubem F.S.,Namboothiri, Irishi N.N.,Bower, John F.,da Silva Júnior, Eufranio N.
, (2020/06/23)
Rhodium-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulations and nitroalkene reactions have been employed for the synthesis of 56 quinone-based compounds. These were evaluated against Trypanosoma cruzi, the parasite that causes Chagas disease. The reactions described here are part of a program that aims to utilize modern, versatile and efficient synthetic methods for the one or two step preparation of trypanocidal compounds. We have identified 9 compounds with potent activity against the parasite; 3 of these were 30-fold more potent than benznidazole (Bz), a drug used for the treatment of Chagas disease. This article provides a comprehensive outline of reactions involving over 120 compounds aimed at the discovery of new quinone-based frameworks with activity against T. cruzi.
Halogen-Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules
Ungati, Harinarayana,Govindaraj, Vijayakumar,Nair, Chithra R.,Mugesh, Govindasamy
, p. 3391 - 3399 (2019/02/13)
The poor uptake of fluorescent probes and therapeutics by mammalian cells is a major concern in biological applications ranging from fluorescence imaging to drug delivery in living cells. Although gaseous molecules such as oxygen and carbon dioxide, hydrophobic substances such as benzene, and small polar but uncharged molecules such as water and ethanol can cross the cell plasma membrane by simple passive diffusion, many synthetic as well as biological molecules require specific membrane transporters and channel proteins that control the traffic of these molecules into and out of the cell. This work reports that the introduction of halogen atoms into a series of fluorescent molecules remarkably enhances their cellular uptake, and that their transport can be increased to more than 95 % by introducing two iodine atoms at appropriate positions. The nature of the fluorophore does not play a major role in the cellular uptake when iodine atoms are present in the molecules, as compounds bearing naphthalimide, coumarin, BODIPY, and pyrene moieties show similar uptakes. Interestingly, the introduction of a maleimide-based fluorophore bearing two hydroxyethylthio moieties allows the molecules to cross the plasma and nuclear membranes, and the presence of iodine atoms further enhances the transport across both membranes. Overall, this study provides a general strategy for enhancing the uptake of organic molecules by mammalian cells.
Synthesis and structure - Phytotoxicity relationships of acetylenic phenols and chromene metabolites, and their analogues, from the grapevine pathogen Eutypa lata
Smith, Leverett R.,Mahoney, Noreen,Molyneux, Russell J.
, p. 169 - 176 (2007/10/03)
Eutypa lata, the fungus responsible for dying-arm disease in grapevines, produces a number of structurally related secondary metabolites, of which eutypine (1) has been implicated as the principal phytotoxin. However, analysis of an E. lata strain from California known to be pathogenic to grapevines showed that eutypine was not present, suggesting that other metabolites could be phytotoxic. Investigation of the relative phytotoxicities of individual metabolites has been limited by insufficient material and lack of a reliable bioassay. Metabolites of particular interest and their precursors were therefore synthesized, and a rapid, quantitative bioassay via topical application of individual compounds to disks of grape leaves and measurement of chlorophyll loss was developed to provide a relative measure of tissue damage. The recently reported metabolite eulatachromene (2) was found to have phytotoxicity greater than that of eutypine (1). The cyclization product, 5-formyl-2-methylvinyl[1]benzofuran (3), also showed significant activity, whereas the reduction product, eutypinol (4), was inactive, as was the quinol, siccayne (5). These results indicate that before strains of Eutypa are incriminated as pathogenic they must be analyzed for the presence or absence of specific constituents for which the phytotoxicity has been unequivocally established.
A concise synthesis of thyroxine (T4) and 3,5,3'-Triiodo-L-thyronine (T3)
Salamonczyk, Grzegorz M.,Oza, Vibha B.,Sih, Charles J.
, p. 6965 - 6968 (2007/10/03)
The mono- and di-iodo derivatives of 1-oxaspiro[2,5]bicycloocta-4,7-dien-6-one, 8 and 9, reacted readily with 3,5-diiodo-L-tyrosine at pH 8.0 to give 3,5,3'-triiodo-L-thyronine (T3) and thyroxine in 70% and 94% yields respectively. In turn, 8 and 9 were prepared by the sodium bismuthate oxidation of their corresponding iodinated p-hydroxybenzyl alcohol derivatives, 6 and 7 in 32% and 37% yields.
Synthesis of Substituted Dibenzophospholes. Part 5. Synthesis of Intermediates for 4- and 6-Aryl Substituents
Buttrus, Nabeel H.,Cornforth, Sir John,Hitchcock, Peter B.,Kumar, Ashok,Stuart, Alan S.
, p. 851 - 858 (2007/10/02)
6-Iodo-5-methoxy-8-methyl-1,2,3,4-tetrahydro-1,4-ethanonaphthalene was prepared from the Diels-Alder adduct of benzoquinone and cyclohexadiene.Diels-Alder condensation of 2-acetamimido-benzoquinone and 2-iodobenzoquinone (convenient, new syntheses of both quinones are described) with 2-methylcyclohexa-1,3-diene led to mixtures of adducts; the major adduct from the iodoquinone was isolated and found by X-ray analysis to have the methyl and iodo substituents at the 2- and 7-positions, respectively, of the 1,4-ethanonaphthalene skeleton.Addition of 2-acetamidobenzoquinone to mentha-2,6,8(9)-triene derived from (-)-carvone gave two regioisomers (structures determined by n.m.r. spectroscopy).In a smooth 4-step synthesis from 6,6-dimethylfulvene and benzoquinone, 6-iodo-9-syn-isopropyl-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-methanonaphthalene was prepared and its stucture confirmed by X-ray analysis.
