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DOI: 10.1039/A803853H (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1998, 3003-3010

Biosynthesis. Part 30.1 Colchicine: studies on the ring expansion step focusing on the fate of the hydrogens at C-4 of autumnaline

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Peter W. Sheldrake, Keith E. Suckling, Robert N. Woodhouse, Amanda J. Murtagh, Richard B. Herbert, Alan C. Barker, James Staunton and Alan R. Battersby

Abstract

Autumnaline 1 is a key biosynthetic precursor of colchicine 4. Syntheses are described of autumnalines that are labelled stereospecifically with tritium at C-4 of their isoquinoline ring. This corresponds to C-12 of the later intermediate dienone 2. Incorporation experiments with the labelled autumnalines using Colchicum autumnale plants show that (a) both HR and HS at C-4 of 1 are fully retained as the dienone is generated, (b) there is stereospecific loss of HS from C-12 of the dienone during the ring expansion process by which the tropolone ring of colchicine is formed and (c) also, there is partial loss (ca. 20%) of the 3H label from the HR position at C-12. These results are rationalised by a proposal for the biosynthesis of colchicine that involves a cyclopropane intermediate in the ring expansion step plausibly formed by a radical process.

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