162131-96-6Relevant articles and documents
Synthesis of sulfur- and sulfoxide-substituted 2,3-oxidosqualenes and their evaluation as inhibitors of 2,3-oxidosqualene-lanosterol cyclase
Zheng, Yi Feng,Oehlschlager, Allan C.,Georgopapadakou, Nafsika H.,Hartman, Peter G.,Scheliga, Petra
, p. 670 - 680 (1995)
2,3-Oxidosqualene (23-OS) analogs that contain thioether (52-55) and sulfoxide (56-60) at positions normally occupied by carbons considered to be cationic during 2,3-oxidosqualene-lanosterol cyclase (OSC) cyclization (C-6, C-10, C-14, and C-19) were synthesized and tested as substrate mimic inhibitors of fungal and mammalian OSC. The analogs were found to be potent inhibitors of cyclase in cell-free extracts of Candida albicans and rat liver. Thioether analogs were more potent than the corresponding sulfoxides. In both series, those 2,3-OS analogs containing a sulfur at the position normally occupied by C-19 were the most potent. With C. albicans cyclase, the IC50 for thioether 55 was 0.0023 μM while 60 exhibited an IC50 of 0.065 μM, which are the lowest values reported for a inhibitor of this enzyme. Similarly, thioether 55 displayed an IC50 of 0.00082 μM for rat liver cyclase which is the best inhibitor up to date for this enzyme. These results suggest that mimics with modification in the region of C-19 of 2,3-OS have a high affinity for the active site of these enzymes. The same series of analogs (52-60) were also tested for inhibition of cholesterol biosynthesis in intact MDBK (Madin Darbin bovine kidney) cells and for in vitro antifungal activity against C. albicans.
Highly Regioselective 5-endo-tet Cyclization of 3,4-Epoxy Amines into 3-Hydroxypyrrolidines Catalyzed by La(OTf)3
Hoshino, Yoshihiko,Iwabuchi, Yoshiharu,Kuriyama, Yuse,Sasano, Yusuke,Uesugi, Shun-ichiro,Yamaichi, Aoto
, p. 1961 - 1965 (2021/01/04)
Highly regioselective intramolecular aminolysis of 3,4-epoxy amines has been achieved. Key features of this reaction are (1) chemoselective activation of epoxides in the presence of unprotected aliphatic amines in the same molecules by a La(OTf)3 catalyst and (2) excellent regioselectivity for anti-Baldwin 5-endo-tet cyclization. This reaction affords 3-hydroxy-2-alkylpyrrolidines stereospecifically in high yields. DFT calculations revealed that the regioselectivity might be attributed to distortion energies of epoxy amine substrates. The use of this reaction was demonstrated by the first enantioselective synthesis of an antispasmodic agent prifinium bromide.
Hydrogen-bond-assisted epoxidation of homoallylic and allylic alcohols with hydrogen peroxide catalyzed by selenium-containing dinuclear peroxotungstate
Kamata, Keigo,Hirano, Tomohisa,Kuzuya, Shinjiro,Mizuno, Noritaka
scheme or table, p. 6997 - 7004 (2009/09/30)
The reaction of peroxotungstates (H2WO4 + H 2O2) with H2SeO4 gave the novel seleniumcontaining dlnuclear tungsten species, (TBA)2[SeO 4{WO(O2)2}2] (I, TBA = [(n-C 4H9)4N]+), which was characterized by elemental analysis, IR, Raman, UV-vls, 77Se NMR, 183W NMR, and CSI-MS. Various kinds of homoallyllc and allyllc alcohols were efficiently epoxldlzed to the corresponding epoxy alcohols In high yields with 1 equlv. H2O2 with respect to thesubstrates. Compound I showed the highest catalytic activity for H 2O2-based epoxldatlon of homoallyllc and allyllc alcohols among selenium and tungsten complexes. The turnover frequency reachedup to 150 h-1 In a 10 mmol-scale epoxldatlon of c/s-3-hexen1 -ol and this value was the highest among those reported for the translt lon-metal catalyzed epoxldatlon of homoallyllc alcohols with H2O2. The kinetic, mechanistic, computational studies showed that the stabilization of the transition-state by the hydrogen bonding between I and the substrates results In the high reactivity for the l-catalyzed epoxldatlon of homoallyllc and allyllc alcohols. The nature of the hetero atoms In the dland tetranuclear peroxotungstates with XO 4n- ligands (X = As(V), P(V), S(VI), SI(IV), etc.) was crucial In controlling the Lewis acidity of the peroxotungstates, which significantly affects their electrophlllc oxygen transfer reactivity. Allthe data of the structural, kinetic, spectroscopic, and computational c omparison show that the dlmerlc peroxotungstate unit, {WO(O2)2} 2, In I Is activated by the SeO42- ligand.
