23978-65-6Relevant academic research and scientific papers
Aryltetralin-lignan formation in two different cell suspension cultures of Linum album: Deoxypodophyllotoxin 6-hydroxylase, a key enzyme for the formation of 6-methoxypodophyllotoxin
Federolf, Katja,Alfermann, A. Wilhelm,Fuss, Elisabeth
, p. 1397 - 1406 (2008/04/12)
Suspension cultures initiated from two different Linum album seedlings accumulate either podophyllotoxin (PTOX, 2.6 mg/g DW) or 6-methoxypodophyllotoxin (6MPTOX, 5.4 mg/g DW) as main lignans. Two molecules of coniferyl alcohol are dimerized to pinoresinol which is converted via several steps into deoxypodophyllotoxin (DOP) which seems to be the branching point to PTOX or 6MPTOX biosynthesis. DOP is hydroxylated at position 7 to give PTOX by deoxypodophyllotoxin 7-hydroxylase (DOP7H). In contrast, 6MPTOX biosynthesis is achieved by DOP hydroxylation at position 6 to β-peltatin by the cytochrome P450 enzyme deoxypodophyllotoxin 6-hydroxylase (DOP6H). The following methylation to β-peltatin-A-methylether is catalyzed by β-peltatin 6-O-methyltransferase (βP6OMT) from which 6MPTOX is formed by hydroxylation at position 7 by β-peltatin-A-methylether 7-hydroxylase (PAM7H). DOP6H and βP6OMT could be characterized in protein extracts from cell cultures of L. flavum and L. nodiflorum, respectively, and here in L. album for the first time. DOP7H and PAM7H activities could not yet be detected with protein extracts. Experiments of feeding DOP together with inhibitors of cytochrome P450 depending as well as dioxygenase enzymes were performed in order to shed light on the type of DOP7H and PAM7H. Growth parameters and specific activities of enzymes from the phenylpropane as well as the lignan specific biosynthetic pathway were measured during a culture period of 16 days. From the enzymes studied only the DOP6H showed a differential activity sustaining the hypothesis that this enzyme is responsible for the differential lignan accumulation in both cell lines.
β-peltatin 6-O-methyltransferase from suspension cultures of Linum nodiflorum
Kranz, Kerstin,Petersen, Maike
, p. 453 - 458 (2007/10/03)
S-Adenosyl-L-methionine:β-peltatin 6-O-methyltransferase was isolated and characterized from cell suspension cultures of Linum nodiflorum L. (Linaceae), a Linum species accumulating aryltetralin lignans such as 6-methoxypodophyllotoxin. The enzyme transfers a methyl group from S-adenosyl-L-methionine to the only free OH-group of β-peltatin in position 6 thus forming β-peltatin-A methylether. This reaction is a putative biosynthetic step in the biosynthesis of 6-methoxypodophyllotoxin from deoxypodophyllotoxin. The enzyme has a pH-optimum at pH 7.7 and a temperature optimum at 40 °C. The enzyme activity is strongly inhibited by MnSO 4, FeCl3, FeSO4 and ZnSO4 as well as S-adenosyl-homocysteine. Mg2+ and EDTA did not influence the methylation of β-peltatin. Substrate saturation curves were obtained for S-adenosyl-methionine and β-peltatin and apparent Km-values of 15 μM and 40 μM, respectively, were determined for these substrates. Substrate inhibition was observed for β-peltatin. No other lignan substrate tested nor caffeic acid were accepted. The suspension cell line of Linum nodiflorum was characterized with respect to growth, medium alterations and lignan production as well as activity of SAM:β-peltatin 6-O-methyltransferase. Highest specific activities of β-peltatin 6-O-methyltransferase were determined on day 7 of the culture period corresponding to the highest levels of 6-methoxypodophyllotoxin on days 7 to 12.
Studies on the Constituents of the Seeds of Hernandia ovigera L. IV. Syntheses of β-Peltatin-A and -B Methyl Ethers from Desoxypodophyllotoxin
Yamaguchi, Hideo,Nakajima, Syunji,Arimoto, Masao,Tanoguchi, Mariko,Ishida, Toshimasa,Inoue, Masatoshi
, p. 1754 - 1760 (2007/10/02)
Two kinds of 4-aryltetralin type lignans, β-peltatin-A methyl ether (I-A) and β-peltatin-B methyl ether (I-B), were synthesized from desoxypodophyllotoxin (DPT), which is available in large quantities from the seeds of Hernandia ovigera L. (Hernandiaceae).The syntheses were achieved via demethylene-DPT (IV), 8-bromo-demethylene-DPT (V) and 8-bromo-DPT (VI).Methylenation of V was carried out successfully by using cesium fluoride and methylene iodide in DMF.Compound I-B was readily obtained by the reaction of VI with cuprous iodide and sodium methoxide in the presence of pyridine.Synthesis of I-A was only achieved by the reaction of lithiated VI with nitrobenzene at -100 deg C in the presence of tetramethylethylene diamine, and I-A was obtained in low yield, together with I-B.Keywords Hernandia ovigera; 4-aryltetralin lignan; desoxypodophyllotoxin (DPT); desoxypicropodophyllin (DPP); 2'-bromo-desoxypodophyllotoxin; 8-bromo-desoxypodophyllotoxin; beta-peltatin-A methyl ether; beta-peltatin-B methyl ether; lithiated desoxypodophyllotoxin; lignan X-ray analysis
SYNTHESE TOTALES DE LA (+/-) ISO β-PELTATINE ET DE SES ANALOGUES
Brown, Eric,Loriot, Michel,Robin, Jean-Pierre
, p. 949 - 952 (2007/10/02)
α-Hydroxyalkylation of a β-(2-alkoxy 3,4-methylenedioxy benzyl)-γ-butyrolactone (17 or 25) with 3,4,5-trimethoxybenzaldehyde or syringaldehyde 27, followed by cyclisation, afforded good yields of the corresponding (+/-) isopeltatins.
Synthesis of (+/-)-Iso-β-peltatin-A Methyl Ether
Mallaiah, M.,Hazra, B. G.,Das, K. G.
, p. 434 - 435 (2007/10/02)
Synthesis of (+/-)-Iso-β-peltatin-A methyl ether utilising sequential substitution of the β- and α-positions of butenolide followed by acid cyclisation is presented.
