具有光學活性的β-環糊精 (β-cyclodextrin; β-CD)雖然常被利用在對掌性分子的分離上，但是由於β-CD結構上具備C7對稱軸且不帶有電荷，因此分離效率不高且侷限了其應用範圍。本研究中，我們合成出以poly (amido amine) (PAMAM) 樹枝狀分子衍生修飾的β-CD單、雙取代衍生物，以降低其高度對稱性，並讓其外圍帶有多重正電荷，增加在對掌性分離與辨識上的應用性。我們先以發散途徑製備出第一代(G1)、第二代(G2)、第三代(G3)之核心帶有丙炔基，尾端帶有多重胺基團的PAMAM樹枝狀分子，接著在一價銅催化下與帶有疊氮基團的β-CD進行點擊偶合反應，而得到一系列高度水溶性且帶有多重正電荷的β-CD衍生物。而為了比較取代數目不同的β-CD衍生物在對掌性分子分離上的差異，我們利用高效率的點擊反應分別合成出兩種類型的衍生物：一是在β-CD六號碳位置接上一個G2分子，得到單取代衍生物;另一種是利用位向選擇性反應先合成出在六號A、D碳位置上(6A、6D)帶有雙疊氮基團的β-CD分子，再分別接上一個G1分子而得到雙取代衍生物。經過透析及冷凍乾燥法得到β-CD衍生物後，我們利用酸鹼滴定法調整溶液的pH值並進行核磁共振光譜分析，進一步探討樹枝狀分子骨架上三級胺和一級胺的質子化程度。當pH值越小 (pH＝2)，樹枝狀分子骨架上的一級胺和三級胺完全被質子化，；當pH值越大 (pH＝11.9)，骨架上一級胺和三級胺則完全呈現中性狀態；而pH值接近中性時(pH＝7.9)，骨架上的一級胺會被質子化而三級胺仍呈現中性狀態。藉由核磁共振光譜分析便可以定義出樹枝狀分子骨架質子化程度的差異，也證實了調整pH值可以有效控制β-CD衍生物的正電荷密度。我們預期單取代G2、雙取代G1兩種類型的β-CD衍生物在pH值為中性的環境下具有相同電荷數目，但由於對稱性不同，因此在對掌性分子分離與辨識上會產生不同的效果。
Optical active β-cyclodextrin (β-CD) often serves as the chiral selector for the separation of enantiomers. However, because of its higher C7 symmetry and non-ionic peripherals, β-CD only shows moderate chiral discrimination efficiency toward limited racemic pools. In the present research, mono- and bis-poly (amido amine) (PAMAM) dendrons-substituted β-CD derivatives were successfully synthesized to reduce the intrinsic symmetry of unmodified β-CD and to yield multiple positive charges on the primary face. G1 and G2 NH2-terminated PAMAM dendrons were prepared through divergent pathway using propargylamine as the focal point, and then copper(I)-catalyzed Huisgen [2 + 3] dipolar cycloaddition reaction (click reaction) successfully conjugated the azide-functionalized β-CD and thus-prepared PAMAM dendrons. Mono and bis-adduct were obtained by the conjugation of mono-azido-functionalized β-CD with the G2 PAMAM dendron and by the coupling of regioselective 6A,6D-bis(azido)-substituted β-CD with two G1 PAMAM dendrons via click reaction, respectively. After dialysis and lyophilization to give final highly water-soluble β-CD/PAMAM complexes, the protonation level of internal tertiary amines and peripheral primary amines was adjusted by pH titration. The 1H NMR analysis clearly indicated that the primary amines were completely protonated but the tertiary amine remains in neutral state at neutral pH, which allows us to control the charge density of these β-CD derivatives by using suitable pH buffer. We also anticipate the mono and bis-PAMAM-substituted β-CD derivatives, bearing lower C1 and C2 symmetry and multiple positive charges, could be the considerable chiral selectors for the separation of anionic enatiomeric pairs.
