5524-25-4Relevant articles and documents
Cytochrome P450-Catalyzed Hydroxylation Initiating Ether Formation in Platensimycin Biosynthesis
Rudolf, Jeffrey D.,Dong, Liao-Bin,Zhang, Xiao,Renata, Hans,Shen, Ben
supporting information, p. 12349 - 12353 (2018/09/27)
Platensimycin (PTM) and platencin (PTN) are potent and selective inhibitors of bacterial and mammalian fatty acid synthases. The regio- and stereospecificity of the ether oxygen atom in PTM, which PTN does not have, strongly contribute to the selectivity and potency of PTM. We previously reported the biosynthetic origin of the 11S,16S-ether moiety by characterizing the diterpene synthase PtmT3 as a (16R)-ent-kauran-16-ol synthase and isolating 11-deoxy-16R-hydroxylated congeners of PTM from the ptmO5 mutant. PtmO5, a cytochrome P450, was proposed to catalyze formation of the ether moiety in PTM. Here we report the in vitro characterization of PtmO5, revealing that PtmO5 stereoselectively hydroxylates the C-11 position of the ent-kaurane scaffold resulting in an 11S,16R-diol intermediate. The ether moiety, the oxygen of which originates from the P450-catalyzed hydroxylation at C-11, is formed via cyclization of the diol intermediate. This study provides mechanistic insight into ether formation in natural product biosynthetic pathways.
Synthesis, in vitro antimalarial activity and in silico studies of hybrid kauranoid 1,2,3-Triazoles Derived from Naturally Occurring Diterpenes
De Santos, Juliana O.,Pereira, Guilherme R.,Brand?o, Geraldo C.,Borgati, Tatiane F.,Arantes, Lucas M.,De Paula, Renata C.,Soares, Luciana F.,Do Nascimento, Maria F.A.,Ferreira, Marlia R.C.,Taranto, Alex G.,Varotti, Fernando P.,De Oliveira, Alaíde B.
, p. 551 - 565 (2016/03/19)
We herein report the synthesis of hybrid kauranoid molecules of type 1,2,3-triazole-1,4-disubstituted aiming to improve the antimalarial activity of kaurenoic and xylopic acids. The CuI-catalyzed cycloaddition of azides and kauranoid terminal a
Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines
Ukiya, Motohiko,Sawada, Shingo,Kikuchi, Takashi,Kushi, Yasunori,Fukatsu, Makoto,Akihisa, Toshihiro
, p. 177 - 188 (2013/04/23)
Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC50 values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4′,4′,4′-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC50 values in the range of 1.2-4.1 μM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity. Copyright
