Synthesis of labelled precursors of podophyllotoxin
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Podophyllotoxin is an aryltetralin lignan and anticancer agent produced by the Podophyllum and some other species and is extracted from Podophyllin in up to 30 percent yield. Little definitive information is available on the biosynthetic pathways to podophyllotoxin. Administering various specifically labelled precursors into intact plants and tissue cultures can give a much improved insight into the lignan biogenesis. The first part of the work has been to the synthesis of two diastereotopically labelled with 2H at C-4. Desoxypodophyllotoxin is the penultimate intermediate of the podophyllotoxin pathway and specifically labelled compounds can be used for the C-4 hydroxylation studies. Doubly 2H labelled desoxypodophyllotoxin at C-4 was also prepared which can be used for a control experiment. This work also led to the unambiguous assignment of the proton nmr of desoxypodophyllotoxin. A second part of the work has been the synthesis of p-coumarlc acid, a known lignan precursor, doubly labeled with 2H or 2H and 13C at the C-3â position. This labeling was selected because the availability of a C-3-labeled monomeric precursor would thus make possible the isolation and study of dimeric compounds labeled at this key positions. These compounds were synthesized, and their identity and stereochemistry were determined by spectroscopic and analytical techniques. The isotopic incorporation of these compounds was 95% d, or d2 (or greater), as determined by mass spectral analysis.
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