Synthesis of Colchicine Derivatives

Abstract

WHILE the methoxylated carbon-system of (IV) is conclusively established for certain degradation products of colchicine^1,2, the synthesis of such unsymmetrically substituted dibenzcycloheptatrienes, necessary for further work, has hitherto miscarried, because of difficulties which are partly concealed and partly apparent^2–4. A synthesis which promises to afford the requisite degree of adaptability has now been found and is based on the oxidation of appropriate 9- or 10-methylphenanthrenes with osmium tetroxide in benzene-pyridine^5,6. In a model experiment, 9-methylphenanthrene (I) was thereby oxidized to 9 : 10-dihydroxy-9: 10-dihydro-9-methylphenanthrene (II), m.p. 130-131° (found: C, 79.9 ; H, 6.1 ; C₁₅H₁₄O₂ requires C, 79.7 ; H, 6.2 per cent), from which, by cleavage with lead tetra-acetate and renewed cyclization, there was obtained the known 3 : 4 : 5 : 6-dibenzcyclohepta-1: 3 : 5-trien-7-one (III)². Similarly, 2 : 3 : 4: 7-tetramethoxy-10-methylphenanthrene, m.p. 134–135° (found: C, 73.2 ; H, 6.4 ; C₁₉H₂₀O₄ requires C, 73.1 ; H, 6.4 per cent), Was converted via the corresponding 9: 10-dihydro-9 : 10-diol, m.p. 156° (found: C, 66.0 ; H, 6.4 ; C₁₉H₂₂O₆ requires C, 65.9 ; H, 6.4 per cent) into the unsaturated ketone (IV), which was identical with the part-product previously obtained¹ by oxidizing deaminocolchinol methyl ether with sodium dichromate in acetic acid.