Methylenedioxy bridge

The following table lists common names, position of ring substitution, and approximate activity of the amphetamine derivatives for some readily available allyl and propenyl benzenes (see J. Chromatography 30,54(1967) for further information on these compounds). Activity is relative to mescaline which equals 1 (an activity of 12 means a dose of about 25 mg). Parentheses indicate a methylenedioxy bridge other substituents are methoxy groups. 

The oxidative cyclization of an ortho-hydroxy-methoxy-substituted aromatic system giving a methylenedioxy group is also known to involve a cytochrome P-450-dependent mono-oxygenase. This enzyme hydroxylates the methyl to yield a formaldehyde hemiacetal intermediate, which can cyclize to the methylenedioxy bridge (the acetal of formaldehyde) by an ionic mechanism (Figure 2.21). 

BAUER, W., ZENK, M.H., Two methylenedioxy bridge forming cytochrome P-450 dependent enzymes are involved in (5)-stylopine biosynthesis. Phytochemistry, 1991,30,2953-2961. 

RUEFFER, M., ZENK, M.H., Canadine synthase from Thalictrum tuberosum cell cultures catalyzes the formation of the methylenedioxy bridge in berberine synthesis. Phytochemistry, 1994, 36, 1219-1223. 

The formation of the methylenedioxy bridge in Berberis has been found to be caused by the demethylating activity of a peroxidase (POD) found within the vesicle. It was also found that the cytochrome P450-requiring enzyme (canadine synthase) from microsomes of Berberis, Thalictrum and Coptis species formed the methylene bridge in (S)-tetrahydrocolumbamine (Ikezawa et al, 2003), but not in the quaternary alkaloid columbamine (Galneder et al, 1988 Zenk, 1995). Because of the substrate specificity of canadine s)mthase, the berberine pathway is considered to be that presented in Fig. 2.5 (Rueffer and Zenk, 1994). Columbamine, once proposed as an alternative route to berberine, is however converted to palmatine by a specific methyltransferase first isolated from Berberis wilsoniae cell cultures (Rueffer and Zenk, 1985 Ikezawa et al, 2003). 

Microsomal, cytochrome P450-dependent enz)unes isolated from the cells of E. californica convert (S)-scoulerine to (S)-stylopine by the introduction of methylenedioxy bridges (Bauer and Zenk, 1991). This conversion is catalysed by P450-dependent s)mthases (chalanthifoline and stylopine synthase) (Facchini, 2001 Ikezawa et al., 2007). The subsequent N-methylation requires... 

Figure 4.10 Biosynthesis of sesamin by the sequential introduction of two methylenedioxy bridges into pinoresinol by the c)4 ochrome P450 CYP81Q (Ono et al., 2006).

As indicated above, the methylenedioxy bridge of yatein is formed wifh 4, 5 -dimefhylfhujaplicatin as a substrate. The methylenedioxy bridge of bursehemin is, however, direcfly infroduced at the level of matairesinol prior to the methylation of the 4 -OH group (Sakakibara et al, 2003). 

Jiao, Y., Davin, L.B. and Lewis, N.G. (1998) Furanofuran lignan metabolism as a function of seed maturation in Sesamum indicum methylenedioxy bridge formation. Phytochemistry, 49, 387-94. 

Ono, E., Nakai, M., Fukui, Y, Tomimori, N., Fukuchi-Mizutani, M., Saito, M., Satake, H., Tanaka, T., Katsuta, M., Umezawa, T. and Tanaka, Y. (2006) Formation of two methylenedioxy bridges by a Sesamum CYP81Q protein yielding a furofuran lignan, (+)—sesamin. Proc. Natl. Acad. Sci. USA., 103,10116-21. 

Inouye K, Sato F. Molecular cloning and characterization of CYP719, a methylenedioxy bridge-forming enzyme that belongs 51. to a novel P450 family, from cultured Coptis japonica cells. J. 

Shamma and Moniot are of the opinion that the methylenedioxy bridge between the rings A and D in thalpenine (32) is formed during the biogenesis via the oxonium ion from the methoxyl group (430). 

Ikezawa, N., K. Iwasa, and F. Sato, Molecular cloning and characterization of methylenedioxy bridge-forming enzymes involved in stylopine biosynthesis in Eschscholzia califomica. FEBSJ., 2007. 274(4) p. 1019-35. 

Diaz Chavez, M. L., et al.. Characterization of two methylenedioxy bridge-forming cytochrome P450-dependent enzymes of alkaloid formation in the Mexican prickly poppy Argemone mexicana. ArcA Biochem. Biophys., 2011. 507(1) p. 186-93. 

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