Synthetic Studies of Natural Coumarins

Zeghdi, Saad (1988) Synthetic Studies of Natural Coumarins. MSc(R) thesis, University of Glasgow.

Abstract

The main emphasis of the work has been directed towards the synthesis of naturally occurring coumarins possessing the relatively rare trans-3-hydroxy-1-methy1but-1-enyl side chain. Initially, work was undertaken to establish the structure of a possibly pharmacologically-active new natural coumarin, CM-c2, isolated in Japan in 1985, for which two stereoisoineric structures were possible. From previous investigations it was believed that photo-oxygenation-reduction of osthol, 7-methoxy-8-(3-methylbut-2-enyl)coumarin, should give CM-c2. After improvements were made to a previously reported synthesis of osthol, photo-oxygenation-reduction was found to proceed by a different pathway. However, this afforded a synthesis of a co-occurring natural coumarin, CM-c1. A method was successfully established for the introduction into a coumarin nucleus of a trans-3-hydroxy-3-rnethylbut-1-enyl side chain using the palladium acetate-catalysed Heck condensation of halocoumarins with 2-methylbut-3-en-2-ol. In this way a variety of 3- and 8-substituted coumarins were prepared including the naturally occurring coumarins, CM-C2, swietenocournarin G and seselin. Controlled dehydration of CM-C2 provided a synthetic route to another natural coumarin, trans---dehydroosthol and established the stereochemistry of the former. The relationship of CM-C2 to murraol, a coumarin first reported in mid-1987, has been clarified. Epoxidation of trans-3-hydroxy-3-methylbut-1-enylcoumarins using meta-chioroperbensoic acid gave the corresponding trans-1,2-epoxy-3-ols in good yields. Attempts were made to transform these epoxyalcohols into the corresponding 2,3-epoxy-1-ols by the Payne rearrangement but without success. However, a study of a non-coumarin model compound showed that the desired rearrangement could be brought about. Heck reactions with 3-methylbut-2-en-1-ol were also studied and shown to give 1-hydroxy-3-methylbut-3-en-2-ylaryl compounds.

• Item Type: Thesis (MSc(R))
• Qualification Level: Masters
• Keywords: Pharmacology
• Date of Award: 1988
• Depositing User: Enlighten Team
• Unique ID: glathesis:1988-77611
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 14 Jan 2020 11:53
• Last Modified: 14 Jan 2020 11:53
• URI: https://theses.gla.ac.uk/id/eprint/77611