Synthetic Studies of Natural Coumarins and Chromones

Hogg, Thomas C (1972) Synthetic Studies of Natural Coumarins and Chromones. PhD thesis, University of Glasgow.

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A variety of methods have been investigated by many workers for the synthesis of ortho-3,3-dimethylallylphenols. However, all of these synthetic routes have their limitations. One method, developed in this laboratory for the synthesis of naturally occurring oxygenated coumarins, besides being more efficient, has the advantages of utilising a preformed coumarin nucleus and mild conditions for the three step isoprenoid insertion process. In this present study, the method has been extended to the synthesis of two natural coumarins, sesibiricin and toddaculin and now provides a viable synthetic route to substitution at C-6 or C-8 of the coumarin nucleus through Claisen rearrangement of the appropriate 1,1-dimethylallyloxy ether. As an alternative synthetic route to sesibiricin, the para Claisen rearrangement of 5-0-(3,3-dimethylallyl)-7-methoxycoumarin has been used for isoprenylation at C-8. Thermal pyrolyses of the 3,3-dimethylallyl ethers of 7-mono and 5,7-dioxygenated chromones, as in the analogous coumarin series, can give a complex mixture of products resulting from cyclisation and abnormal Claisen rearrangement. However, these disadvantages have been overcome by trapping the first formed phenol as the butyrate ester followed by mild hydrolysis which generally affords the phenol. The major drawback to the synthesis of ortho-3,3-dimethylallyl phenols via Claisen rearrangement of 1,1-dimethylallyl ethers has been the initial propargylation step. Attempts were made to improve the efficiency of this step and eventual application of the route to 5,7-dihydroxy-2-methylchromone afforded the isopentenylchromones, peucenin and heteropeucenin. Oxidative cyclisation of peucenin and its 7-methyl ether was achieved through epoxidation of the isoprenoid chain in situ followed by selective nucleophilic ring opening by the ortho hydroxyl groups. Cyclisation with the 7-hydroxyl of peucenin gave a mixture of the secondary alcohol, hamaudol and the tertiary alcohol, visamminol which were separable by acetylation. Oxidative cyclisation of peucenin-7-methyl ether showed that angular cyclisation with the chelated 5-hydroxyl group of the chromone was also a competitive reaction. These results have been confirmed by numerous epoxidation experiments are in complete disagreement with a recent publication which suggests that hamaudol is the sole product of the epoxidation of peucenin.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry, Pharmacology
Date of Award: 1972
Depositing User: Enlighten Team
Unique ID: glathesis:1972-78596
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:09
Last Modified: 30 Jan 2020 15:09

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