Podophyllotoxin biosynthetic pathway

Figure 8.6 Podophyllotoxin biosynthetic pathway. DIR, dirigent protein PLR, pinoresinol-lariciresinol reductase SDH, sec-oisolariciresinol dehydrogenase PS, pluviatolide synthase OMT3, O-methyltransferase 3 CYPx, cytochromes P450 (CYP71CU1) OMT1, O-methyltransferase 1 and 2-ODD,...

Figure 4 Redox reactions in biosynthetic pathways. A one-electron oxidation of two coniferyi aicohoi monomers is the initiating step in podophyllotoxin biosynthesis, and a simiiar one-eiectron oxidation piays a key role in the biosynthesis of the aikaioid morphine. Redox reactions are also used to crosslink nascent scaffoids, as shown for vancomycin, or to add oxygen-based functionality to reduced scaffoids, as shown for taxoi.

Considerable progress has also been made in elucidating the biosynthetic pathway leading to the podophyllotoxin series (scheme 2) [38,39]. Dewick et al. have shown that demethylyatein (15a) and yatein (15b) are precursors of demethylpodophyllotoxin (18a) and podophyllotoxin (18b) respectively. Furthermore, 4 -demethyl-deoxypodophyllotoxin (16a) and deoxypodophyllotoxin (16b) undergo aromatic hydroxylation to yield a-peltatin (17a) and p-peltatin (17b) respectively. They have also shown that (-)-matairesinol (13) is efficiently incorporated into 4 -demethylpodophyllotoxin (18a), podophyllotoxin (18b), a-peltatin (17a) and p-peltatin (17b). These facts have been interpreted as indicating that matairesinol is a common precursor of both the 3,4,5-trimethoxyphenyl and 4-hydroxy-3,5-dimethoxyphenyl series. 

SCHEME 10.6 Biosynthetic pathway from coniferyl alcohol (40) to (-)-podophyllotoxin (39) via (-)-matairesinol (45). 

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