BQC為喜樹鹼之衍生物，經活性評估顯示，BQC為一具有良好抗腫瘤活性的藥物，透過將其接上葡萄糖醛基並留以甲酯的方式，而使BQC成為葡萄糖酸苷前驅藥物甲酯型式，以增加其對腫瘤細胞的專一性及溶解度。BQC的合成是Dr. Masamichi Sugimori以化合物6和7縮合而成，而化合物6是以起始物1進行硝化反應再進行氧化反應，製備化合物5，隨後再還原反應而得到化合物6。其中硝化反應除了會產生對位的主產物4外，也會產生鄰位的副產物2，及鄰位和對位雙取代的副產物3，由於對位的主產物4與鄰位副產物2為同分異構物，其物理性質很接近因此需以管柱層析進行純化。在硝化與氧化二個反應中的個別產率分別為13%及 69%，總產率只有10%，因此本實驗修正反應路徑的順序，以相同的起始物1先進行氧化反應再硝化反應後而得到中間產物5，氧化及硝化兩個反應的個別產率分別為42.7%及77.6%，總產率為33%。根據本實驗修正反應路徑，製備化合物5，產率增加了三倍以上。接著我們應用前驅藥物的概念，設計合成BQCG甲酯型式的化合物，企圖增加對腫瘤細胞的專一性，以提升在臨床上的應用價值。本實驗主要針對過去研究中BQC的合成步驟加以修飾。 5, 6-Dihydro-4H-benzo[de]quinolone camptothecin (BQC), a derivative of camptothecin, has been identified as a potential anti-tumor drug. Additionally, BQC could be conjugated with a methyl glucuronate to improve its tumor specificity and also its water solubility. Dr. Masamichi. firstly synthesized compound 6 from compound 1 through nitrification, oxidation and reduction. Compound 6 then was conjugated with compound 7 to give BQC. However, when the start material is compound 1, the nitrification step would produce a 6-nitro and 6, 8-dinitro byproduct, thus it requires purification of the 8-nitro main product. The yield of nitrification and oxidation is 13.0% and 77.4%, respectively, the total yield is just 10%. In our study, in order to increase the total yield, we modified the synthesis process. We obtained compound 5 by using the same starting material (compound 1) but with different orders, which are oxidation and nitrification. The yield of oxidation and nitrification is 42.7% and 69%, respectively. The total yield is 33%. It is 3-folds better than the original process. In order to improve the practicality of clinical applications by increased the tumor targeting, we were according to the strategy of prodrug. We have been designed and synthesized a BQCG -ester type compound.
