15340-83-7Relevant articles and documents
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.
Stereocontrolled total synthesis of (±)-totaryl methyl ether and (±)-semperviryl methyl ether
Das, Swati,Bhattachryya, Sukanta,Mukherjee, Debabrata
, p. 9101 - 9110 (2007/10/02)
Stereocontrolled synthesis in racemic form of the title diterpene ethers is described. Friedel-Crafts acylation of the naphthalene derivative 15 afforded the methyl ketone 16 in high yield. The compounds 5 and 16 were converted into the hydrophenanthrenones 6 and 7 respectively. Reductive methylation of 6 and 7 in anhydrous ammonia furnished the β, γ-unsaturated ketones 8 and 9 which were stereoselectively transformed into the trans-fused ketones 10 and 11. Huang-Minlon reduction of 10 and 11 afforded the octahydrophenanthrene 27 and (±)-totaryl methyl ether (2) respectively. Friedel-Crafts acylation of 27 provided the methyl ketone 28 which was converted into (±)-semperviryl methyl ether (4).
