一、對掌 -酮醯胺之不對稱還原反應 二、Cisplatin類似物之設計合成

Abstract

本論文主要分為兩個部分，摘要如下： 第一部分在探討對掌-酮醯胺之不對稱還原反應。以具有樟腦架構之N-tosyl camphorpyrazolidinone 70為對掌輔助劑，製備其-酮醯胺衍生物74、76-79為起始物，進行不對稱還原反應。實驗結果顯示：以L-Selectride為還原劑時，雖僅得到中等產率（65-81%）之非鏡像異構物，但可得到不錯之非鏡像超越值（94% de）。且由X-ray單晶繞射解析得知：苯環取代基之副產物80b之絕對立體組態為R-form，故其主產物之絕對立體組態為S-form（若取代基為2-噻吩時，則主產物為R-form）。 第二部分為設計合成具有反式-(-)-(1R,2R)-二胺基環己烷及羧酸根官能基之cisplatin類似物。在醋酸條件下，將反式-(-)-1,2-二胺基環己烷145與L-酒石酸146作用，得到(R,R)-form之白色化合物147後，再將之與氯亞鉑酸鉀在水中反應，可得到具有兩個反式-(-)-1,2-二胺基環己烷官能基之鉑複合物148，產率64%。1H-NMR譜圖中，可見複合物148之構形會隨溫度及時間變化而不同，其分子結構經由1H-NMR、13C-NMR、H-H COSY、NOESY、HMQC及HRMS鑑定確認。

The dissertation is divided into two sections, they are as follows： I. Diastereoselective reduction of N-tosyl camphorpyrazolidinone 70 derived -keto amides 74、76-79. Treatment of -keto amides 74、76、79 with L-Selectride gave moderate chemical yield (65-81%) and good stereoselectivity (94% de). The absolute configuration of the newly generated stereogenic center in the minor diastereomer 80b was determined to have an R-configuration, as deduced from a single X-ray crystal analysis. II. Synthesis of trans-(-)-(1R,2R)-diaminocyclohexane and carboxylate substituted cisplatin analogues. The colored compound 147 was prepared from trans-(-)-1,2-diaminocyclohexane 145 and L-tartaric acid 146 in acetic acid. The platinum complex 148 was synthesized in 64% yield by reacting potassium tetrachloro-palatinate with complex 147. 1H-NMR spectral data of variable-temperature in the range 25-55℃ and variable-time in the range of 0 h to 18 h at room temperature of platinum complex 148 revealed that the proton resonances exchanged 148A for 148B form. The structure of the platinum complex 148 was further confirmed by 1H-NMR、13C-NMR、H-H COSY、NOESY、HMQC and HRMS.