Syntheses in the Colchicine Series

Jack, James (1951) Syntheses in the Colchicine Series. PhD thesis, University of Glasgow.

Abstract

In part I it has been shown that the ring closure of certain diphenylyl propionic acids does not lead to dibenzocycloheptadienone derivatives. These cyclisation products are indanone derivatives. In part II the expansion of the central ring of several 9- and 10- methylphenanthrenes to dibenzocyclo-heptatrienone derivatives has been examined. Ring expansion can be achieved in three stages viz. (1) formation of a 9:10-diol (2) cleavage of the diol to a keto-aldehyde which is (3) cyclised to give the required type of product. Optimum conditions for the cyclisation stage have been found. When 2:3:4:7-tetramethoxy-9-methylphenanthrene was submitted to the above process 9:12:13:14-tetramethoxy-3:4-5:6-dibenzocyclohepta-3:5:7-trien-2-one was formed. Hydrogenation of the latter afforded 9:12:13:14-tetramethoxy-3:4-5:6-dibenzocyclohepta-3:5-dien-2-one. The oxime of the last named compound was hydrogenated to give (+)-2-amino-9:12:13:14-tetramethoxy-3:4-5:6-dibenzocyclohepta-3:5-diene (I) which was resolved by means of (+)-6:6'-dinitro-diphenic acid. The resulting laevorotatory form of (I) was shown to be identical with (-)-colchinol methyl ether obtained by degradation of colchicine. The structure of the last named product is thereby firmly established. In part III (+)-2-hydroxy-9:12:13:14-tetramethoxy- 3:4-5:6-dibenzocyclohepta-3:5-diene is described. It has been shown to be structurally distinct from the (-)-carbinol formed by the action of nitrous acid on colchinol methyl ether. The latter reaction involves a Demjanow rearrangement, accompanied by some racemisation, affording (-)- and (+)-9:10-dihydro-9-hydroxymethyl-2:3:4:7-tetramethoxyphenanthrene. The (+)- form of the latter has been synthesised and converted, by dehydration, to 9:12:13:14-tetramethoxy-3:4-5:6-dibenzocyclohepta-1:3:5-triene. The dihydro derivative of the latter proved identical with dihydrodeaminocolchinol methyl ether. By the action of nitrous acid (+)-9:10-dihydro-9-aminomethyl-2:3:4:7-tetramethoxyphenanthrene has been converted to deaminocolchinol methyl ether. In part IV a total synthesis of colchicine has been envisaged but the initial step viz. the hydrogenation of ring C of N-acetylcolchinol or its methyl ether, has not been realised.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1951
• Depositing User: Enlighten Team
• Unique ID: glathesis:1951-78878
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 14:54
• Last Modified: 30 Jan 2020 14:54
• URI: https://theses.gla.ac.uk/id/eprint/78878