471-79-4Relevant academic research and scientific papers
ZnI2/Zn(OTf)2-TsOH: A versatile combined-Acid system for catalytic intramolecular hydrofunctionalization and polyene cyclization
Chou, Ting-Hung,Yu, Bo-Hung,Chein, Rong-Jie
supporting information, p. 13522 - 13525 (2019/11/14)
A mild and efficient combined-Acid system using a zinc(ii) salt [ZnI2 or Zn(OTf)2] and p-Toluene sulfonic acid (TsOH) was investigated for catalytic cationic cyclizations, including intramolecular hydrocarboxylation, hydroalkoxylation, hydroamination, hydroamidation, hydroarylation and polyene cyclizations. This reaction provides easy access to five-and six-membered O-and N-containing saturated heterocyclic compounds, tetrahydronaphthalene derivatives and polycyclic skeletons in excellent yield with perfect Markovnikov selectivity and under mild conditions. The operational simplicity, broad applicability, and use of inexpensive commercially available catalysts make this protocol superior to existing methodologies.
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.
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.
The synthesis and antibacterial activity of totarol derivatives. Part 1: Modifications of ring-C and pro-drugs
Evans, Gary B.,Furneaux, Richard H.,Gravestock, Michael B.,Lynch, Gregory P.,Scott, G.Kenneth
, p. 1953 - 1964 (2007/10/03)
A series of analogues of, and potential pro-drugs derived from, the potent antibacterial diterpene totarol (1) were synthesized in order to elucidate the minimum structural requirements for antibacterial activity and to seek compounds with good bioavailability in vivo. These analogues varied in the structural features of their aromatic rings and the prodrugs were O-glycosylated derivatives. They were tested in vitro against three Gram-positive bacteria: β-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA); and against the Gram-negative multi-drug-resistant Klebsiella pneumoniae. None of the analogues was more potent than totarol itself, which is effective against these Gram-positive bacteria at MIC values of 7 μM. The results were evaluated in terms of a structure-activity relationship and this showed that a phenolic moiety was essential for potent antibacterial activity. Amongst the pro-drugs, totaryl α-D-mannopyranoside (22) proved the most active in vitro (MIC 18 μM). The in vivo antibacterial activities of compounds 1, 22 and totarol β-lactoside (23) were assessed in a mouse model of infection, but they were found to be ineffective. Compounds 1 and 22 were shown to be cytotoxic towards proliferating human cell cultures, CH 2983, HeLa, and MG 63, but only at concentrations of > 30 μM.
Stereoselective intramolecular 6-exo-Heck reaction : A facile synthetic route to podocarpa-8,11,13-triene and diterpenoid resin acids intermediates
Mukhopadhyaya, Jayanta K.,Ghosh, Ajit K.,Ghatak, Usha Ranjan
, p. 835 - 837 (2007/10/03)
Intramolecular Heck reaction of the olefins 1a-c in the presence of sodium formate affords ca 3:1 mixtures of the respective trans- and cis-octahydrophenanthrenes 3a-c and 4a-c. Similar reaction of the olefmic ester 2 provides a 70:30 mixture of (±)-methyl desisopropyldehydroabietate 6 and (±)10-epi-methyl desoxypodocarpate 7.
AN EFFICIENT SYNTHESIS OF 2-SUBSTITUTED 3,3-DIMETHYLCYCLOHEXAN-1-ONES. A SIMPLE SYNTHETIC ROUTE TO PODOCARPA-8,11,13-TRIENE INTERMEDIATES.
Banik, Bimal K.,Chakraborti, Asit K.,Ghatak, Usha Ranjan
, p. 3391 - 3397 (2007/10/02)
2-Substituted 3,3-dimethylcyclohexan-1-ones are conveniently prepared from the respective 2-substituted 3-methylcyclohex-2-en-1-ones through boron trifluoride-ether-mediated conjugate addition of a methyl group with lithium dimethylcuprate and those incorporating 2β-phenylethyl substituents have been further transformed to podocarpa-8,11,13-triene intermediates in excellent yields.
