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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Stereodivergent synthesis of 2-oxo-oligopyrrolidines by an iterative coupling strategy
Yasuki Soda1, Kumpei Tatsumi1, Matteo Forner1,2
1Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1, Hiyoshi, Kohoku-ku, Yokohama, 223-8522, Japan. t-okamura@applc.keio.ac.jp.
Abstract:
Natural linear polyamines play diverse roles in physiological processes by interacting with receptors at the cellular level. Herein, we describe the stereodivergent synthesis of oligopyrrolidines, which are conformationally constrained polyamines. We synthesized dimeric and trimeric 2-oxo-oligopyrrolidines using an iterative coupling strategy. The key to our success is an iridium-catalyzed trans/cis-selective nucleophilic addition and subsequent threo/erythro-stereoselective reduction. The synthesized pyrrolidines show varying cytotoxicities against a human cancer cell line depending on the number of rings and their stereochemistry.
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