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Updated: Mar 12, 2026

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
Published on: April 27, 2017
From Lead to Drug Utilizing a Mannich Reaction: The Topotecan Story
1Department of Pharmacy, Center for Drug Research, Ludwig-Maximilians University, Munich, Germany.
Abstract:
Natural products are a rich source of bioactive compounds, and numerous natural compounds have found application in cancer chemotherapy. However, unfavorable physicochemical properties often prevent the use of the original natural product as a drug. A prominent example is camptothecin from the Chinese tree Camptotheca acuminata, which shows extraordinary cytotoxic activity based on a specific molecular mode of action (inhibition of human topoisomerase I). Due to its extremely poor solubility, the original natural product cannot be used as a drug. The marketed drug topotecan was developed from this lead structure by semi-synthesis utilizing a Mannich aminomethylation as the crucial step. In this review, the long-distance run leading to this drug and further perspectives are summarized.
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