Abstract:
Tetrasubstituted tetrahydrofuran lignans are natural products which exhibit a host of biological activities and are potential candidates as drug compounds. Previously the total syntheses of a series of these lignans has employed the acyl-Claisen rearrangement as the key reaction to generate stereodefined compounds. This thesis describes the syntheses and studies of six novel α-fluoro-α,β-disubstituted morpholine amides 83 – 87 generated using an acyl-Claisen rearrangement process. These novel fluorinated amide compounds were characterized and compared to their non-fluorinated counterparts. A number of these amides were converted into 5-membered iodolactones 101a – 103a and comprehensively analysed using NMR techniques to determine that the stereochemistry of 2- and 3- substituents of the fluorinated amides are in a syn relationship. The applicability of the fluorinated amides in the syntheses of fluorinated analogues of tetrahydrofuran lignans was demonstrated through the conversion of amide 83 to precursor alcohol 108 using the same synthetic route towards the natural tetrahydrofuran lignan galbegin (4).
