22555-67-5Relevant articles and documents
Design, synthesis and anthelmintic activity of 7-keto-sempervirol analogues
Crusco, Alessandra,Bordoni, Cinzia,Chakroborty, Anand,Whatley, Kezia C.L.,Whiteland, Helen,Westwell, Andrew D.,Hoffmann, Karl F.
supporting information, p. 87 - 100 (2018/05/07)
The plant-derived, diterpenoid 7-keto-sempervirol was recently reported to display moderate activity against larval stages of Schistosoma mansoni (IC50 = 19.1 μM) and Fasciola hepatica (IC50 = 17.7 μM), two related parasitic blood and liver flukes responsible for the neglected tropical diseases schistosomiasis and fascioliasis, respectively. Here, we aimed to increase the potency of 7-keto-sempervirol by total synthesis of 30 structural analogues. Subsequent screening of these new diterpenoids against juvenile and adult lifecycle stages of both parasites as well as the human HepG2 liver cell line and the bovine MDBK kidney cell line revealed structure-activity relationship trends. The most active analogue, 7d, displayed improved dual anthelmintic activity over 7-keto-sempervirol (IC50 ≈ 6 μM for larval blood flukes; IC50 ≈ 3 μM for juvenile liver flukes) and moderate selectivity (SI ≈ 4–5 for blood flukes, 8–13 for liver flukes compared to HepG2 and MDBK cells, respectively). Phenotypic studies using scanning electron microscopy revealed substantial tegumental alterations in both helminth species, supporting the hypothesis that the parasite surface is one of the main targets of this family of molecules. Further modifications of 7d could lead to greater potency and selectivity metrics resulting in a new class of broad-spectrum anthelmintic.
Alkyldisulfanium salts: Isolable, electrophilic sulfur reagents competent for polyene cyclizations
Schevenels, Florian T.,Shen, Minxing,Snyder, Scott A.
, p. 2 - 5 (2017/11/27)
Tools that can effect electrophilic sulfur-promoted cation-π cyclizations are generally lacking, especially using alkylsulfide-based reagents. Herein we report that combining three different 1,2-dithioethers with Cl2 and SbCl5 generates isolable alkyldisulfanium salts that can effect such reactions. These new reagents can install -SMe, -SEt, and -SCH2CH2CF3 in modest, moderate, or good yield on diverse frameworks, including polyenes that terminate with electron-deficient groups. We also show that reagents such as dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) can accomplish similar chemistry.
Highly enantioselective proton-initiated polycyclization of polyenes
Surendra, Karavadhi,Corey
supporting information; experimental part, p. 11992 - 11994 (2012/09/08)
This report describes the synthesis of a range of chiral polycyclic molecules (tricyclic to pentacyclic) from achiral polyene precursors by enantioselective proton-initiated polycyclization promoted by the 1:1 complex of o,o′-dichloro-BINOL and SbCl5. Excellent yields (ca. 90% per ring formed) and enantioselectivety (20:1 to 50:1) were obtained. The process is practical as well as efficient, because the chiral ligand is both readily prepared from R,R- or S,S-BINOL and easily recovered from the reaction mixture by extraction.