Abstract
Abstract This thesis describes the use of the Diels-Alder cycloaddition reaction between diester 57 and diene 78 for the purpose of achieving the total synthesis of natural products of a high degree of structural complexity. Specifically, the first chapter details the total synthesis of (±)-teucvin (44) and (±)-12-epi-teucvin (45) while the second describes the total synthesis of (±)-montanin A (46) as well as the research geared towards eventual total synthesis of (±)-montanin B (47) and (±)-12-epi-montanin B (48). All of the above mentioned naturally occurring compounds are from the Teucrium family which has been a constant source of clerodanoid natural products, a class under which 44-48 all fall under. Starting with dienophile 57, Diels-Alder cycloaddition of which with diene 78 furnished tricyclic enone 79. Subsequent 1,4-addition of a methyl group onto the corresponding acetate furnished ketone 82. Base hydrolysis of 82 then allowed for the generation of ketone 108 which was subsequently subjected to a series of reactions including hydrogenation, Jones oxidation, and an acid promoted cyclization and dehydration to give lactone 111. Finally, lactone 111 was carried through to the end of the total synthesis endeavor via the conversion of its carboxyl to an aldehyde via the corresponding acid chloride, treatment of the resulting aldehyde with 3-furyllithium followed by a base promoted cyclization of the ensuing addition product furnished (±)-teucvin (44) and (±)-12-epi-teucvin (45). Towards the montanin series of natural products (i.e. 46-48), ketone 87 was oxidized with Jones reagent and the resulting intermediate was reduced by Dibal-H in a highly regioselective manner to furnish furan 119. Oxidation of the hydroxyl of furan 119 was achieved by treatment with Fétizon’s reagent to give aldehyde 122, treatment of which with 3-furyllithium followed by base allowed for the completion of the total synthesis of (±)-montanin A (46). Towards the total synthesis of 47 and 48, furan 120 was oxidized with PDC to yield enone 130 which was subsequently reduced by treatment with sodium cyanoborohydride to give a mixture of epimeric alcohols 135 and 136. It is envisioned that alcohols 135 and 136 would be suitable advanced intermediates for the total synthesis of naturally occurring 47 and 48. The results of these and the above mentioned research and studies constitutes the body of this thesis.