Synthetic Studies of Natural Coumarins

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