Abstract
This dissertation consists of two partsPart I. First Total Syntheses of (±)-Annuionone B and (±)-TanarifuranonolThe intramolecular Diels-Alder reaction of cyclohexa-2,4-dien-1-one obtained from a 2-methylphenol I and isobutenol II provided the cycloaddition product III. Ozonolysis of the tricyclic adduct IV quickly furnished the 6-oxabicyclo[3.2.1]octane core V of the natural product annuionone B and tanarifuranonol. After several convenient functional group transformations, the strategy was then successfully applied to the synthesis of racemic annuionone B (VII). A potential intermediate VI - also led to the synthesis of the proposed structure of tanarifuranonol. To the best of our knowledge and after comparison of all spectral data, we propose compound VIII, which is an epimer of IX and has a different configuration at the chiral center bearing the hydroxyl functional group, to be the structure of the isolated natural product.Part II. Development of Novel Anti-Influenza Virus AgentsBPR2P series were the novel anti-influenza virus agents which were discovered by National Health Research Institute. In this thesis, more the 40 analogs from BPR2P series were synthesized for lead optimization. And In order to improve the drug properties of BPR2P compounds, simplification of the chemical structure of BPR2P compounds was also attempted. We synthesized coumarin derivatives XI and also benzofuran derivatives XII and checked their activities. The results showed that the furanocoumarin core structure was essential to maintain the anti-influenza activity.We also designed a novel synthesis route which can avoid the predicament form simple synthesis pathway. We used the 2,4-dihydroxy acetophenone XIII as starting material; the ortho-lithiation method was next applied to introduce the side chain to get compound XIV. Benzofuran moiety XV was first synthesized without using Fries rearrangement. Then the coumarin structure was constructed by using an intra-molecular Wittig type reaction led to final BPR2P analogs. In all, it takes 11 synthetic steps, but only five purification stages are required. By using this novel synthetic approach, several BPR2P analogs with tender substitutions were synthesized. Those compounds are crucial in the SAR study of BPR2P compounds.