Cell cultures of Ruta graveolens

The monomeric acridone alkaloids are derived from anthranilic acid and acetate via a polyketide. First studies, in which [ C]-acetate was utilized by cell cultures of Ruta graveolens, indicated that the C-ring of the acridone nucleus was acetate derived. Further research revealed that anthranilic acid is specifically incorporated into the A-ring of rutacridone (Baumert et al, 1982). 

Baumert, A., Porzel, A., Schmidt, J. and Groger, D. (1992) Formation of 1,3-dihydroxy-N-methylacridone from N-methylanthranoyl-GoA and malonyl-CoA by cell cultures of Ruta graveolens. Z. Naturforsch., 47c, 365-8. 

Purification of a furanocoumarin 0-methyltransferase from cell cultures of Ruta graveolens L. J, Chromatogr, 157 427-431. 

Dictamnine (7, R = Me) was a specific precursor of skimmianine (7, R = Me, 7,8-diOMe) and other furoquinoline alkaloids oxygenate in the aromatic ring in Skimmia japonica and Choisya ternate [41] similar results were obtained with cell cultures of Ruta graveolens [104]. Dihydro- (5) and furoquinolin-4-ones (8) are also known. 

Steck, W., B. K. Bailey, J. P. Shyluk, and O. L. Gamborg Coumarins and Alkaloids from Cell Cultures of Ruta graveolens. Phytochemistry 10, 191 (1971). 

Baumert, A., Kuzovkina, N.I., Krauss, G., Hieke, M. and Groger, D. (1982) Biosynthesis of rutacridone in tissue cultures of Ruta graveolens (L.). Plant Cell Rep., 1,168-71. 

Baumert, A., Maier, W., Groger, D. and Deutzmarm, R. (1994) Purification and properties of acridone synthase from cell suspension cultures of Ruta graveolens (L.). Z. Naturforsch., 49c, 26-32. 

Supporting evidence for the biosynthetic pathway to the furoquinoline alkaloids gleaned in whole plants comes from an investigation using cell suspension cultures of Ruta graveolens, which produced furoquinoline bases and edulinine (151). ... 

An acridone synthase respraisible for the conversion of Af-methylanthraniloyl CoA and malonyl CoA into l,3-d3iydroxy-Af-methylacridone (33, Scheme 24.10) has been purified from cell suspensimi cultures of Ruta graveolens and characterized [115,116]. The essential Af-methylatiOTi of the starter substrate was supported also by the anthrani-late Af-methyhransferase activity detected in crude extracts of R. graveolens cells [117]. 

Boulanger D, Bailey BK, Steck W (1973) Formation of edulinine and furoquinoline alkaloids from quinoline derivatives by cell suspension cultures of Ruta graveolens. Phytochemistry 12 2399-2405... 

Maier, W., Baumert, A., Schumarm, B., Furukawa, H. and Groger, D. (1993) Synthesis of 1,3-dihydroxy-N-methylacridone and its conversion to rutacridone by cell-free extracts of Ruta graveolens cell cultures. Phytochemistry, 32, 691-8. 

Rohde B, Hans J, Martens S, Baumert A, Hunziker P, Matem U (2008) Anthranilate N-methyltransferase, a branch-point enzyme of acridone biosynthesis. Plant J 53 541-553 Maier W, Schumann B, Groger D (1990) Biosynthesis of acridone alkaloids formation of rutacridone by cell-free extracts of Ruta graveolens cell suspension cultures. FEBS Lett 263 289-291... 

JUNGHANNS, K.T., KNEUSEL, R.E., BAUMERT, A, MAIER, W GROGER, D., MATERN, U., Molecular cloning and heterologous expression of acridone synthase from elicited Ruta graveolens L cell suspension cultures, Plant Molec. Biol., 1995, 27, 681-692. 

Maier et al. have observed that microsomes (from Ruta graveolens cell cultures) catalyze the condensation of 1,3-dihydroxy-lO-methylacridin-9(10//)-one 69 with isopentenyl p5Tophosphate or dimethylallyl pyrophosphate, in the presence of NADPH and O2, to produce rutacridone 327, and also that the reaction involved glycocitrine-II 265 as an intermediate (90MI2 93P691). A possible precursor 351 of rutacridone 327 has also been isolated from a reaction of glycocitrine-II 265 with m-chloroperbenzoic acid (MCPBA) (Scheme 67) (93CPB383). 

The biosynthetic pathway to rutacridone, which was isolated from Ruta graveolens (Rutaceae), was studied in detail using the cell culture method [4,5]. According to these results, the biosynthetic precursors of rutacridone are anthranilic acid, acetic acid, and an isopentenyl unit, as in the case of the quinoline alkaloids described in the previous section. However, in the biosynthesis of rutacridone, two additional C2 units participate in the biosynthesis of the acridone nucleus compared with the biosynthesis of quinoline alkaloids. 

A number of reductive biotransformations of acyl silanes into a-hydroxy silanes have appeared recently. Acetyl dimethylphenylsilane is converted into (/f)-(l-hydroxyethyl) dimethylphenylsUane by plant cell suspension cultures of Symphytum officinale L. and Ruta graveolens L. in low yields but in 81% ee and 6% ee, respectively . SUanol and disUoxane were observed as by-products. Microbial reduction of racemic acetyl t-butyldimethylsilane has been achieved using Trigonopsis variabilis (DSM 70714) and Corynebacterium dioxydans (ATCC 21766) on a 10- gramme scale with > 96% ee in each case and in up to 78% yield . Recently, Saccharomyces cerevisiae (DHWS 3), a commercially available form of bakers yeast, has been shown to reduce acetyl dimethylphenylsilane, again to (/ )-(1-hydroxyethyl) dimethylphenylsilane, in 40% yield and >99.5% ee . 

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