H. Pelish, N. Westwood, Y. Feng
Jun 16, 2001
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Influential Citations
167
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Quality indicators
Journal
Journal of the American Chemical Society
Abstract
diversity-oriented synthesis to construct a library based on a natural product, galanthamine (2, Figure 1), with the goal of discovering molecules that exhibit biological effects beyond those previously associated with the natural product. Although 2 is a potent acetylcholinesterase inhibitor, 8 our aim was not to improve this activity. Galanthamine was selected because it offered a range of functionality for diversity-generating reactions, it presented a rigid polycyclic core that might lower the potential entropy penalty associated with protein binding, and it allowed for the use of powerful biomimetic reactions in the synthesis. 9 In this communication, we report a biomimetic solid-phase synthesis of 2527 molecules based on the alkaloid natural product galanthamine and the identification of a molecule from the library that perturbs the secretory pathway in mammalian cells 10 sa process unrelated to the acetylcholinesterase inhibitory activity of 2.