本論文研究包含兩個部份：第一部份是利用N,N-二異丙基-10-樟腦磺醯胺29作為掌性輔助基衍生之1,3-二口咢環戊-4-酮化合物36為起始物，進行奎寧酸前驅物65a的不對稱形式合成研究與LdT 96的不對稱形式合成研究；第二部份是以核心結構144為骨架來開發高潛力的組織蛋白酶S抑制劑。

I. (a) 在奎寧酸前驅物的不對稱形式合成研究方面：利用內酯縮酮化合物59為起始物衍生之化合物88與1,3-丁二烯進行不對稱Diels-Alder反應，得到乙醇酸衍生物69的前驅物93、94，合併總產率為39%，選擇性為4.9：1；或是利用內酯縮酮化合物36為起始物，進行不對稱的烷基化反應和ring-closing metathesis反應兩個關鍵步驟，共用了七步完成奎寧酸前驅物65a的合成，總產率33%。

(b) 在LdT的不對稱形式合成研究方面：利用內酯縮酮化合物36為起始物與alpha-三甲基矽烷丙烯醛131進行不對稱的醇醛反應，得到單一產物的1,2-相鄰雙醇130，共用了三步完成LdT前驅物123的合成，總產率37%。

II. 在開發高潛力的組織蛋白酶S抑制劑方面：修飾核心結構144上的苯環來合成一系列的144衍生物與合成alpha-酮醯胺衍生物179，可惜並未找到高潛力的組織蛋白酶S抑制劑。

This thesis consists of two parts. The first part was concerned with application of chiral 1,3-dioxolan-4-ones 36, derived from (1S)-(+)-N,N-diisopropyl-10-camphorsulfonamide 29, in enantioselective formal synthesis of precursor of (-)-quinic acid 65a and LdT 96. In the second part, discovering high potent Cathepsin S inhibitors based on skeleton of core structure 144 is described.

I. (a) Enantioselective formal synthesis of precursor of (-)-quinic acid: Asymmetric Diel-Alder reaction of dienophile 88, derived from 1,3-dioxolan-4-ones 59, with 1,3-butadiene afforded precursors of glycolic acid 69 derivatives, 93, 94 in 39% yield. The diastereoselective ratio of Diel-Alder reaction is 4.9 : 1. On the other hand, A seven-step synthesis, including diastereoselective alkylation and ring-closing metathesis reactions, of precursor of (-)-quinic acid 65a from 1,3-dioxolan-4-ones 36 has been achieved in 33% overall yield.

(b) Enantioselective formal synthesis of precursor of LdT: Aldol reaction of the enolate of 1,3-dioxolan-4-one 36 with alpha-trimethylsilyl acrolein 131 afforded corresponding product 130. A three-step synthesis of precursor of LdT 123 from aldol adduct 130 has been furnished in 37% overall yield.

II. Discovery of potent Cathepsin S inhibitors: Synthesis of various core structure 144 derivatives and alpha-ketoamide 179 for inhibition of Cathepsin S. Unfortunately, those compounds has low IC50 value of Cathepsin S.

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