Autumnaline, biosynthesis

Definitive evidence arising from and H-labelling studies points to the intermediacy of (5)-autumnaline (124) in the biosynthesis of colchicine (125). The incorporation of (i S)-[l- C]autumnaline [as (124)] into colchicine (125), with enhancement of the n.m.r. signal for C-7 only, affirms this conclusion. 

Nasreen, A., M. Rueffer, and M.H. Zenk (1996). Cytochrome P-450-dependent formation of isoan-drocymbine from autumnaline in colchicine biosynthesis. Tetrahedron Lett. 37, 8161-8164. 

Nasreen A, Rueffer M, Zenk MH (1996) Cyto-ehrome P 50-dependent formation of isoandro-eymbine from autumnaline in eolehieine biosynthesis. Tetrahedron Lett 37 8161-8164... 

Woodhouse RN, McDonald E, Ramage R, Battersby AR (1998) Biosynthesis. Part 29. Colchicine studies on the ring expansion step focusing on the fate of the hydrogens at C-3 of autumnaline. J Chem Soc Perkin Trans 1 2995-3001... 

The crucial test for the hypothesis lay in the examination of compounds of type 6.171) and 6.173) as colchicine precursors. In the event [119-121], 0-methylandrocymbine 6.172) was a spectacularly good precursor for colchicine. The phenethylisoquinoline 6.171), called autumnaline, was also clearly implicated in biosynthesis only the (5)-isomer of autumnaline, with the same absolute configuration as colchicine is involved, and oxidative coupling of this base occurs in a para-para sense rather than the alternative, ortho-para. Results of other experiments, together with those discussed here, led to the pathway illustrated in Scheme 6.34. 

As demonstrated for the biosynthesis of benzyltetrahy-droisoquinoline alkaloids in the previous section of this chapter, different aryl-aryl coupling reactions affect structurally diverse carbon skeletons for the resulting secondary metabolites. As shown in Scheme 12.9, oxidative phenolic ortho-para coupling of autumnaline results in the formation of floramultine (46), a prominent member of the homoapor-phine family of alkaloids, which can be isolated from several families of higher plants [29],... 

Several genera of the Liliaceae plant family have been identified to produce the secondary metabolite autumnaline (45), which also serves as key intermediate in the biosynthesis of a variety of phenethylisoquinoline alkaloids (see Schemes 12.9 and 12.10). Colchicine (54), derived from autumnaline (45) via a remarkable ring-expanding rearrangement, is the most prominent member of this class of tyrosine-derived alkaloids. 

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