29549-60-8Relevant articles and documents
Enantioselective syntheses of sulfoxides in octahedral ruthenium(II) complexes via a chiral-at-metal strategy
Li, Zheng-Zheng,Wen, A-Hao,Yao, Su-Yang,Ye, Bao-Hui
supporting information, p. 2726 - 2733 (2015/03/30)
The preparation of chiral 2-(alkylsulfinyl)phenol compounds by enantioselective coordination-oxidation of the thioether ruthenium complexes with a chiral-at-metal strategy has been developed. The enantiomerically pure sulfoxide complexes δ-[Ru(bpy)2{(R)-LO-R}](PF6) (bpy is 2,2′-bipyridine, HLO-R is 2-(alkylsulfinyl)phenol, R = Me (δ-1a), Et (δ-2a), iPr (δ-3a), Bn (δ-4a), and Nap (δ-5a)) and δ-[Ru(bpy)2{(S)-LO-R}](PF6) (R = Me (δ-1a), Et (δ-2a), iPr (δ-3a), Bn (δ-4a), and Nap (δ-5a)) have been synthesized by the reaction of δ-[Ru(bpy)2(py)2]2+ or δ-[Ru(bpy)2(py)2]2+ with the prochiral thioether ligands 2-(alkylthio)phenol (HL-R), followed by enantioselective oxidation with m-CPBA as oxidant. The X-ray crystallography was used to verify the stereochemistry of ruthenium complexes and sulfur atoms. The configurations of the ruthenium complexes are stable during the coordination and oxidation reactions. Moreover, the chiral sulfoxide ligands are enantioselectively generated by controlling of the configuration of ruthenium centers in the course of oxidation reaction. That is, the δ configuration at the ruthenium center generates the S sulfoxide ligand; on the contrary, the δ configuration of the ruthenium complex originates the R sulfoxide ligand. Acidolysis of δ-[Ru(bpy)2{(R)-LO-R}](PF6) and δ-[Ru(bpy)2{(S)-LO-R}](PF6) complexes in the presence of TFA-MeCN afforded the chiral ligands (R)-HLO-R and (S)-HLO-R in 96-99% ee values, respectively. Importantly, the chiral ruthenium complexes can be recycled as δ/δ-[Ru(bpy)2(MeCN)2](PF6)2 and reused in a next reaction cycle with complete retention of the configurations at ruthenium centers.
Covalent modification of cyclooxygenase-2 (COX-2) by 2-acetoxyphenyl alkyl sulfides, a new class of selective COX-2 inactivators
Kalgutkar, Amit S.,Kozak, Kevin R.,Crews, Brenda C.,Hochgesang Jr., G. Phillip,Marnett, Lawrence J.
, p. 4800 - 4818 (2007/10/03)
All of the selective COX-2 inhibitors described to date inhibit the isoform by binding tightly but noncovalently at the substrate binding site. Recently, we reported the first account of selective covalent modification of COX-2 by a novel inactivator, 2-acetoxyphenyl hept-2-ynyl sulfide (70) (Science 1998, 280, 1268-1270). Compound 70 selectively inactivates COX-2 by acetylating the same serine residue that aspirin acetylates. This paper describes the extensive structure-activity relationship (SAR) studies on the initial lead compound 2-acetoxyphenyl methyl sulfide (36) that led to the discovery of 70. Extension of the S-alkyl chain in 36 with higher alkyl homologues led to significant increases in inhibitory potency. The heptyl chain in 2-acetoxyphenyl heptyl sulfide (46) was optimum for COX-2 inhibitory potency, and introduction of a triple bond in the heptyl chain (compound 70) led to further increments in potency and selectivity. The alkynyl analogues were more potent and selective COX-2 inhibitors than the corresponding alkyl homologues. Sulfides were more potent and selective COX-2 inhibitors than the corresponding sulfoxides or sulfones or other heteroatom-containing compounds. In addition to inhibiting purified COX-2, 36, 46, and 70 also inhibited COX-2 activity in murine macrophages. Analogue 36 which displayed moderate potency and selectivity against purified human COX-2 was a potent inhibitor of COX-2 activity in the mouse macrophages. Tryptic digestion and peptide mapping of COX-2 reacted with [1-14C-acetyl]-36 indicated that selective COX-2 inhibition by 36 also resulted in the acetylation of Ser516. That COX-2 inhibition by aspirin resulted from the acetylation of Ser516 was confirmed by tryptic digestion and peptide mapping of COX-2 labeled with [1- 14C-acetyl]salicyclic acid. The efficacy of the sulfides in inhibiting COX- 2 activity in inflammatory cells, our recent results on the selectivity of 70 in attenuating growth of COX-2-expressing colon cancer cells, and its selectivity for inhibition of COX-2 over COX-1 in vivo indicate that this novel class of covalent modifiers may serve as potential therapeutic agents in inflammatory and proliferative disorders.
Alkylthiolation of Phenols
Ranken, Paul F.,McKinnie, B. Garry
, p. 117 - 119 (2007/10/02)
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