25360-32-1Relevant articles and documents
Structure-Based Design, Synthesis and Biological Evaluation of Bis-Tetrahydropyran Furan Acetogenin Mimics Targeting the Trypanosomatid F1 Component of ATP Synthase
Zacharova, Marija K.,Tulloch, Lindsay B.,Gould, Eoin R.,Fraser, Andrew L.,King, Elizabeth F.,Menzies, Stefanie K.,Smith, Terry K.,Florence, Gordon J.
supporting information, p. 5434 - 5440 (2019/06/10)
The protozoan parasites Trypanosoma brucei, Trypanosoma cruzi and Leishmania spp. are responsible for the severely debilitating neglected Tropical diseases of African sleeping sickness, Chagas disease and leishmaniasis, respectively. As part of our ongoing programme exploring the potential of simplified analogues of the acetogenin chamuvarinin we identified the T. brucei FoF1-ATP synthase as a target of our earlier triazole analogue series. Using computational docking studies, we hypothesised that the central triazole heterocyclic spacer could be substituted for a central 2,5-substituted furan moiety, thus diversifying the chemical framework for the generation of compounds with greater potency and/or selectivity. Here we report the design, docking, synthesis and biological evaluation of new series of trypanocidal compounds and demonstrate their on-target inhibitory effects. Furthermore, the synthesis of furans by the modular coupling of alkyne- and aldehyde-THPs to bis-THP 1,4-alkyne diols followed by ruthenium/xantphos-catalysed heterocyclisation described here represents the most complex use of this method of heterocyclisation to date.
Ring-expanded N-heterocyclic carbene complexes of ruthenium
Armstrong, Robert,Ecott, Christopher,Mas-Marza, Elena,Page, Mkhael J.,Mahon, Mary F.,Whittlesey, Michael K.
, p. 991 - 997 (2010/04/25)
The six-membered N-heterocyclic carbene l,3-bis(2,4,6-trimethylphenyl)-3,4, 5,6-tetrahydropyrimidin2-ylidene (6-Mes) reacts with Ru(PPh3) 3(CO)HF to afford Ru(6-Mes)(PPh3)(CO)HF (1), which is converted to the five-coordinate C-H activated carbene complex Ru(6-Mes)'(PPh3)(CO)H (2) upon treatment with Et3SiH. The hydride chloride precursor Ru(PPh3)3(CO)HCl affords a mixture of products with 6-Mes, but reacts cleanly with 1,3-bis(isopropyl)-3,4, 5,6-tetrahydropyrimidin-2-ylidene (6-1Pr) to give the six-coordinate activated complex Ru(6-1Pr)'(PPh3)2(CO)H (3a), in which the hydride is trans to the methylene arm of the activated NHC. This complex isomerizes in solution with ΔH# and Delta;S# values of 98.2 ± 4.6 kJ mol-1 and 15.5 ± 14.5Jmol -1 K-1.The major product from the isomerization, 3b, in which the hydride ligand is trans to carbene, can be made directly by reaction of 6-1Pr with Ru(PPh3)3(CO)H2.
Catalytic hydrodefluorination of aromatic fluorocarbons by ruthenium N-heterocyclic carbene complexes
Reade, Steven P.,Mahon, Mary F.,Whittlesey, Michael K.
, p. 1847 - 1861 (2009/08/07)
The catalytic hydrodefluorination (HDF) of hexafluorobenzene, pentafluorobenzene, and pen- tafluoropyridine with alkylsilanes is catalyzed by the ruthenium N-heterocyclic carbene (NHC) complexes Ru(NHC)(PPh 3)2(CO)H2 (NHC = SIMes (1,3-bis(2,4,6-trimethylphenyl) imidazolin-2-ylidene) 13, SIPr (1,3- bis(2,6-diisopropylphenyl)imidazolin-2- ylidene) 14, IPr (1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) 15, IMes (1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) 16). Catalytic activity follows the order 15 > 13 > 16 > 14, with 15 able to catalyze the HDF of C6F5H with Et3SiH with a turnover number of up to 200 and a turnover frequency of up to 0.86 h-1. The catalytic reactions reveal (i) a novel selectivity for substitution at the 2-position in C6F5H and C5F5N, (ii) formation of deuterated fluoroarene products when reactions are performed in C 6D6, or C6D5CD3, and (iii) a first-order dependence on [fluoroarene] and zero-order relationship with respect to [R3SiH]. Mechanisms are proposed for HDF of C 6F6 and C6F5H, the principal difference being that the latter occurs by initial C-H rather than C-F activation.
