喜樹鹼具有良好的抗癌效果，但其水溶性極差，為了增加水溶解度，並讓藥物有對腫瘤專一性，先期本實驗室設計合成喜樹鹼葡萄醣醛酸前驅藥(9-ACG和10-HCG)，前驅藥只在腫瘤附近被葡萄醣醛酸酶活化達到標靶作用。據研究顯示，10-HCG對於葡萄醣醛酸酶有較好親和性，但是水溶性卻沒有9-ACG好，因此設計在10-HCG的中間體添加水溶性基團N-methylpiperazine，合成目標物10-HCPG，具有更好的親水性，降低細胞毒性，保留酵素親和力，並對腫瘤有專一性。在合成10-HCPG時，中間體會因為立體障礙，而無法順利與喜樹鹼鍵結，降低產率，本研究為了解決此問題，中間體會先鍵結立體障礙較小的2-amino-5-hydroxybenzaldehyde再與tricyclic ketone縮合，以提高合成產率。 Camptothecin has good anti-cancer activity but have poor water solubility. For improving water solubility, our laboratory designed and synthesized two glucuronide prodrugs of Camptothecin (9-ACG and 10-HCG) which will mainly be activated at tumor site expressing large number of β-glucuronidase. According to previous studies, 10-HCG have good affinity for β-glucuronidase but water solubility is not better than 9-ACG. Therefore, we design and synthesize the target compound 10-HCPG by creating N-methyl piperazine on the spacer of 10-HCG, expect for good water solubility, stable in blood, low cytotoxicity, good affinity with β-glucuronidase and specific to tumor cells. Synthesis of 10-HCPG have a problem which spacer conjugating with 10-hydroxycamptothecin have steric effect. For solving this problem, spacer conjugate with 2-amino-5-hydroxybenzaldehyde which have less steric effect and conjugate with tricyclic ketone with condensation reaction
