固有掌性偶氮冠醚雙橋聯雙芳杯之合成及其對胺基醇之掌性辨識研究

Abstract

本論文主要研究方向為固有掌性偶氮冠醚雙芳杯之合成及其對掌性胺基醇類客體的辨識能力的主客化學。 首先，在NaH做為鹼及DMF作為溶劑的條件下，能以高選擇性合成出對位-鄰位冠醚雙橋聯的雙芳杯化合物7b，作為固有掌性芳杯的前驅物，再修飾上酸根及偶氮基團合成固有掌性化合物12b。將外消旋主體化合物 (+/-)-12b與客體胺基醇類分子進行紫外-可見光初步篩選，發現主體只有對phenyl alaninol (G1)才有紫外-可見光光譜上明顯吸收波長的變化，由400 nm 紅位移到575 nm。 在採用掌性管柱的HPLC成功分離出 (+)-12b與 (-)-12b後，分別對鏡像異構物客體 (R)-G1與 (S)-G1進行紫外-可見光滴定實驗以求得錯合常數Ka。從結果得知 (+)-12b與 (S)-G1的錯合常數較大 (Ka = 557 M-1)，與 (R)-G1的錯合常數則較小 (Ka = 159 M-1)，掌性辨識能力之比值Ka(S) / Ka(R) = 3.84。 將化合物 (+)-12b與 (-)-12b分別對鏡像異構物客體 (R)-G1與 (S)-G1進行NMR滴定實驗，從訊號分裂不同的結果可以得知錯合物 (+)-12b-(R)-G1與 (+)-12b-(S)-G1彼此為非鏡像異構物。 化合物12b與客體的錯合模式主要有三種作用力：(1) 加入G1時，12b的酸根會將G1的-NH2質子化，使其變成帶正電的-NH3+，如此一來和12b的冠醚就可產生靜電力；(2) 12b的酸根與G1的羥基之間可有氫鍵作用力；(3) 12b下緣的掌性芳杯所提供的立體障礙會因具掌性的G1的旋光性而有不同大小的立體阻礙排斥力。

The research goal of this thesis is the synthesis of inherently chiral azobiscalix[8]crown and its chiral recogonition toward aminoalcohols. First, in the condition of NaH as a base and DMF as a solvent, we could obtain 1,3-to-1,2 double bridged biscalix[4]arene compound 7b in high selectivity, which is a good precursor for inherently chiral calix[4]raene. After acidification and adding diazo functional group on 7b, we could obtain inherently chiral compound 12b in 8% yield. UV-vis screening experiment was carried out by adding aminoalcohol compounds to racemic (+/-)-12b. The results showed that only phenyl alaninol, G1, showed red shift in its absorption spectra from 400 nm to 575 nm. Chiral HPLC column was applied in order to separate (+)-12b and (-)-12b. After separation, UV-vis titration experiments were carried out by adding enatiomer (R)-G1 and (S)-G1 to solution of CHCl3 (+)-12b and (-)-12b, respectively, to obtain corresponding constants Ka. The results show that (+)-12b has a bigger binding constant with (S)-G1 (Ka = 557 M-1) and smaller binding constant with (R)-G1 (Ka = 159 M-1). The chiral recognition ratio of Ka(S) / Ka(R) is 3.84. NMR titration experiments were carried out by adding enatiomer (R)-G1 and (S)-G1 to (+)-12b and (-)-12b respectively. We could recognize that complex (+)-12b-(R)-G1 and (+)-12b-(S)-G1 are diastereomers from their different NMR signals splittings.