Synthetic Approaches to Complex Naturally Occurring Coumarins

Mowat, Douglas (1973) Synthetic Approaches to Complex Naturally Occurring Coumarins. PhD thesis, University of Glasgow.

Abstract

Synthetic routes to the naturally occurring coumarins glabralactone and the more complex dentatin have been developed to provide unequivocal proof of their structures. The structure assigned to angelicone, an isomer of glabralactone, has also been synthesised, by an unambiguous pathway. As a consequence of this work, the published structure of angelicone has been shown to be incorrect. A key step in each of these syntheses has been the base-catalysed retro-Michael opening of a chrom-anone ring, to generate a phenolic coumarin containing an ortho senecioyl grouping. Additionally, base treatment in this manner has provided, by coumarin ring opening and alternative reclosure, a method for the efficient synthesis of both 6- and 8-senecioyl-5,7-dioxygenated coumarins. The above described chromanone ring opening and coumarin ring Isomerisation processes have also been utilised in the synthesis of dentatin, a linear chromenocoumarin whose structure had been based on spectroscopic data only. The 1,1-dimethylallyl group at C-8 was introduced by the ortho-Claisen rearrangement of the 7-O-(3,3-dimethylallyl) ether derived from a readily available phenolic chromanocoumarin. The further rearrangements to which this type of alkenyl is prone, were deliberately prevented by having a senecioyl group at C-6. The rapid intramolecular cyclisation of this group with the 7-hydroxyl liberated during the Claisen rearrangement, resulted, in high yield, in the formation of a linear chromanocoumarin having the correct carbon skeleton and oxygenation pattern of the natural product. Further careful reduction and dehydration proceeded smoothly to give pure dentatin. Preliminary investigations have been directed towards the syntheses of some structurally complex natural 4-alkyl coumarins which have recently been shown to possess important physiological activity. The reaction of 2,2-dimethy1-5,7-dihydroxychroman-4-one with acetylene dicarboxylic acid dimethyl ester has given two new isomeric 4-carbomethoxy chromanocoumarins The structures of these have been assigned on both spectroscopic and chemical evidence. Attempts to modify the carbomethoxy group and to induce chromanone ring opening have been made. The corresponding 4-methyl analogues have been prepared and shown to be resistant to oxidation.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Organic chemistry
• Date of Award: 1973
• Depositing User: Enlighten Team
• Unique ID: glathesis:1973-78635
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 30 Jan 2020 15:07
• Last Modified: 30 Jan 2020 15:07
• URI: https://theses.gla.ac.uk/id/eprint/78635