本論文包含兩個部份

第壹部份：天然物(±)-Annuionone B與(±)-Tanarifuranonol之全合成

首先利用2-甲基酚類化合物I與2-甲基烯丙醇II進行氧化與分子內Diels-Alder反應之後，可以得到環化加成的化合物III。接著利用臭氧裂解還原後的參環化合物IV，便能快速的得到天然物annuionone B與tanarifuranonol所具有的6-氧雙環[3.2.1]辛烷核心結構V。接著，再經由數步官能基轉換，便可以成功的得到天然物annuionone (VII)。我們也成功利用合成步驟中的中間產物VI來完成tanarifuranonol的全合成，並且在比較所得到的光譜資料後，發現原本文獻報導所推測的tanarifuranonol的結構IX，原本羥基位向應該加以修正，我們合成的化合物XIII才是當初所分離得到的天然物tanarifuranonol。

第貳部份：新穎抗流行性感冒病毒藥物之發展研究

BPR2P系列化合物X是由國家衛生研究院團隊所發現的新穎抗流感病毒的藥物，在本論文中，主要是藉由合成了超過40個BPR2P系列之衍生物；並且為了尋求改善BPR2P藥物性質的可能性，我們也嘗試改變與簡化了BPR2P系列分子的化學結構：我們合成了薰草素的衍生物XI與苯并□喃的衍生物XII。結果顯示BPR2P系列結構中的□喃并薰草素結構對於其抗流感病毒的活性具有關鍵性的影響。
另外，我們也設計了新穎合成路徑來避免原先利用Fries重排反應所遭遇到的困難。首先，我們用2,4-二羥基乙醯苯XIII作為起始物，先在鄰位引進側鏈得到化合物XIV。接著再合成苯并□喃部份的結構XV，最後利用分子內Wittig類型反應合成結構中薰草素的結構。雖然一共花了11個反應步驟，但是只需要五個純化步驟。利用這個新發展的合成步驟，我們可以順利合成之前方法所無法合成的化合物，並使得結構與活性之關係的研究能更完整。

This dissertation consists of two parts

Part I. First Total Syntheses of (±)-Annuionone B and (±)-Tanarifuranonol

The 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 Agents

BPR2P 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.

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