Olefin metathesis as key step in the synthesis of bioactive compounds: Challenges in the total synthesis of (-)-kendomycin

in Current Organic Synthesis (2012), 9(3), 397-405

In this short review article, we highlight the application of the olefin metathesis reaction as a key step in the total synthesis of (-)-kendomycin, a macrocyclic polyketide ansamycin exhibiting ... [more ▼]

In this short review article, we highlight the application of the olefin metathesis reaction as a key step in the total synthesis of (-)-kendomycin, a macrocyclic polyketide ansamycin exhibiting pronounced activity as an endothelin receptor antagonist and antiosteoporotic agent, as well as important antibiotic potency against multiresistant bacteria and remarkable cytotoxicity versus a series of human tumour cell lines. By selecting this example from the recent literature, we hope to illustrate the great synthetic ability of olefin metathesis, while also revealing some problems encountered in the syntheses. © 2012 Bentham Science Publishers. [less ▲]

Synthesis and Catalytic Evaluation of Ruthenium-Arene Complexes Bearing Imidazol(in)ium-2-thiocarboxylate Ligands

in Organometallics (2011), 30(22), 6133-6142

Five new complexes with the generic formula [RuCl(2)(p-cymene)(SOC.NHC)] (2-6) were isolated in high yields by reacting the [RuCl(2)(p-cymene)](2) dimer with a range of imidazol(in)ium-2-thiocarboxylate ... [more ▼]

Five new complexes with the generic formula [RuCl(2)(p-cymene)(SOC.NHC)] (2-6) were isolated in high yields by reacting the [RuCl(2)(p-cymene)](2) dimer with a range of imidazol(in)ium-2-thiocarboxylate zwitterions bearing cyclohexyl, 2,4,6-trimethylphenyl (mesityl), or 2,6-diisopropylphenyl groups on their nitrogen atoms in CH(2)Cl(2) at -20 degrees C. All the products were fully characterized by IR and NMR spectroscopy, and the molecular structures of [RuCl(2)(p-cymene)(SOC.IMes)] (3) and [RuCl(2)(p-cymene)(SOC.SIMes)] (5) were determined by X-ray diffraction analysis. Coordination of the NHC.COS ligands took place via the sulfur atom. A remarkable shielding of the methine proton on the p-cymene isopropyl group was observed by (1)H NMR spectroscopy for complexes 3-6. It is most likely caused by the aromatic ring current of a neighboring mesityl or 2,6-diisopropylphenyl substituent. The catalytic activity of compounds 2-6 was probed in the ring-opening metathesis polymerization (ROMP) of cyclooctene, in the atom transfer radical polymerization (ATRP) of methyl methacrylate, and in the synthesis of enol esters from 1-hexyne and 4-acetoxybenzoic acid. In all these reactions, the [RuCl(2)(p-cymene)(SOC.NHC)] complexes displayed performances slightly inferior to those exhibited by [RuCl(2)(p-cymene)(NHC)] species that result from the reaction of [RuCl(2)(p-cymene)](2) with NHC.CO(2) inner salts. However, they were significantly better catalyst precursors than the much more robust chelates of the [RuCl(p-cymene)(S(2)C.NHC)PF(6) type obtained by coordination of NHC.CS(2) betaines to the ruthenium dimer. These results suggest that the Ru-(SOC.NHC) motif undergoes a dethiocarboxylation under the experimental conditions adopted for the catalytic tests and leads to the same elusive Ru-NHC active species as the preformed [RuCl(2)(p-cymene)-(NHC)] family of complexes. [less ▲]