阿茲海默氏症（Alzheimer’s disease, AD），為一種腦部神經退化性疾病，在世界各地已經有越來越多的老年人受到影響，目前治療的選擇非常有限。因此，新的AD藥物發展是非常重要的課題。Tournefolic acid B（TAB）和tournefolic acid B ethyl ester（TABE）是從藤紫丹被分離出來具有dibenzooxepine骨架之天然物。TAB和TABE被報導分別對於amyloid (A)蛋白誘發神經毒以及N-methyl-D-aspartate (NMDA)誘發興奮毒性具有神經保護之活性，而神經保護活性的藥物可能是具有改善阿茲海默氏症的潛力。TAB以及TABE在藤紫丹中的含量非常少，而本論文中主要針對TAB和TABE進行全合成之研究，同時合成其衍生物為了進一步測試這些化合物的生物活性。
TAB以及TABE的全合成是由起始化合物7和8以7個步驟和6個步驟合成之，在本研究中，以芐基作為保護基，用來保護羥基，dibenzooxepine骨架是經由Wittig reaction以及Ullmann condensation兩方法合成出，然後丙烯酸的部分是利用Heck reaction合成出來的，最後再利用三氯化硼進行去除芐基反應得到TAB及TABE，3個衍生物也是以類似步驟所合成。
Alzheimer’s disease (AD), a neurodegenerative brain disorder, is affecting more and more elderly all around the world and has limited therapeutic options. Thus, the developments of new AD drugs are of importance. Tournefolic acid B (TAB) and tournefolic acid B ethyl ester (TABE) were previously isolated from Tournefortia sarmentosa, and they possessed dibenzooxepine skeleton. TAB and TABE were found to show neuroprotective effects on amyloid protein-mediated neurotoxicity and on N-methyl-D-aspartate (NMDA)-mediated excitotoxicity, respectively. Compounds with neuroprotective activity may have potential to develop useful drugs for treatment in Alzheimer's disease. Due to limited amounts of TAB and TABE in Tournefortia sarmentosa, in this thesis, the total synthesis of TAB and TABE were carried out. Their derivatives were also synthesized for further study on the biological activity.
The total synthesis of TAB and TABE was carried out in 7 steps and 6 steps, respectively, starting from benzylphosphoniun bromide and 3-benzyloxy-6-bromo-2-hydroxybenzaldehyde. In this research, benzyl groups were used for protection of hydroxyl groups. The Wittig reaction and Ullmann condensation were used to construct the dibenzooxepine skeleton. The Heck reaction was used for coupling acrylic acid moiety to dibenzooxepine skeleton. Finally, boron trichloride was used for debenzylation. In addition
