Alkaloid biosynthesis. Part XVI. Colchicine: origin of the tropolone ring and studies with the C6–C3–C6–C1 system

Abstract

Colchicine (1), isolated from Colchicum autumnale plants which had been fed with (±)-[3-¹⁴C]tyrosine, is degraded to prove that ca. 85% of its total activity is located in the tropolone ring at C-12. It is thereby established that the tropolone system is generated from the aromatic nucleus of tyrosine by a ring-expansion process with inclusion of the benzylic carbon atom. A biosynthetic scheme for colchicine based upon a C₆–C₃–C₆–C₁ precursor is outlined and is tested by experiments with labelled 1 -(5-hydroxy-2-hydroxymethyl-4-methoxyphenyl)-3-(3-hydroxy-4,5-dimethoxyphenyl)propylamine (10). This is not incorporated into colchicine by the plants and the implications of this finding are discussed. The lactone prepared by treatment of the Windaus anhydride (7-benzamido-8,9-dihydro-2,3,4-trimethoxy-7H-benzocycloheptene-5,6-dicarboxylic anhydride)(5) with hydriodic acid is 7-benz-amido-8,9-dihydro-2,3-dihydroxy-7H-benzocycloheptene-5,4-carbolactone (6).