在阿茲海默症中Aβ是一個明顯的治療靶點，目前有許多團隊根據不同的假說擬定各式策略以治療阿茲海默症，而我們專注於開發BACE 1抑製劑。
為了引入螺旋支架的三維性和結構新穎性，第一條路徑參考專利結構以diethyl 3-oxopentanedioate 1為起始物，預計以四步合成製備1,5-dibromo-3-methoxypentane，由於第二步之醚化反應不易進行，改將醇基以疊氮官能基進行取代，但均無法得到預期的疊氮化合物而是雙鍵副產物Diethylpent-2-enledioate 7，由於反應不易，改以1,5-dibromopentane 10為起始物與市售6-Bromo-1-indanone 11進行耦合反應，但反應無法如期進行。
第二條路徑選擇以天然核苷為主結構，以Uridine 13作為起始物，經過六步合成以獲得1-[2’,3’-Bis-O-(benzyl)-4’α-hydroxymethyl-β-D-ribopentofuranosyl]uracil 19後再與各式酸耦合以得其衍生物，之後再將1-[2’,3’-Bis-O-(benzyl)-4’α-hydroxymethyl-β-D-ribopentofuranosyl]uracil 19經兩步合成製備得1-[2’,3’-Bis-O-(benzyl)-4’,4’-bis(azidomethyl)-D-ribopentofuranosyl]uracil 21，其可用於往後之醯胺衍生物製備，這些化合物將可用於生物分析以挑選出最有潛力之新型藥物。

The prominent role played by accumulation of Aβ fragments during progression of Alzheimer disease makes it an attractive therapeutic target for small molecule development. This thesis is regarding the preparation of spironucleosides for inhibiting beta secretase enzymes
Initially, we attempted to prepare 1,5-dibromo-3-methoxypentane from the starting compound diethyl 3-oxopentanedioate in a four-step procedure. After several attempts in etherification reaction in the second step, another strategy adopting azido functionality was used. No desired azide compound but only the eliminated by-product diethylpent-2-enledioate. We finally coupled a truncated 1,5-dibromopentane with commercially available 6-bromo-1-indanone, but the reaction could not proceed as expected.
The second route was thus selected from natural nucleosides. Starting from uridine via six-step synthesis of silyl protection on the 5’-position of uridine, benzyl introduction, deprotection, oxidation, aldol condensation to give dihydroxy derivatives, di-triflate formation and diazide formation, t bis(azidomethyl)-D-ribopentofuranosyl]uracil was obtained in total 5.8 % yield. To a purpose of preliminary assessment, the dihydroxy nucleoside analog obtained in 20.6% yield was firstly coupled with a number of carboxylic acids to give the nucleoside ester analogs. The subsequent biological activities with respect of the beta-secretase was performed in due course.

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