Designed to Synthetic Benzyl Ether-Linked Glucuronide Derivative of Benzo[de]quinoline camptothecin(BQC) for Selective Anticancer Therapy
2013
Hochschulschrift
Zugriff:
101
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.
Titel: |
Designed to Synthetic Benzyl Ether-Linked Glucuronide Derivative of Benzo[de]quinoline camptothecin(BQC) for Selective Anticancer Therapy
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Autor/in / Beteiligte Person: | Chou, Hua-Cheng ; 周華晟 |
Link: | |
Veröffentlichung: | 2013 |
Medientyp: | Hochschulschrift |
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