Total Synthesis of Isodaphlongamine H by Iridium‐Catalyzed Reductive [3 + 2] Cycloaddition of <i>N‐</i> Hydroxylactam
Abstract
Abstract The total synthesis of isodaphlongamine H based on a lactam strategy, which enables quick access to complex cyclic amines, is described. The strategy begins with alkylation of a chiral lactam and subsequent N ‐oxidation via an imino ether to afford the N ‐hydroxylactam. For the key transformation to functionalize the amide carbonyl, an iridium‐catalyzed reductive [3 + 2] cycloaddition of the N ‐hydroxylactam provides a tricyclic isoxazolidine in a one‐pot process. After the coupling reaction with an allylic silane fragment, the total synthesis is accomplished through intramolecular Hosomi–Sakurai allylation to construct a pentacyclic core. The deoxygenated pentacyclic intermediate shows higher cytotoxicity against HeLa and U937 cell lines than isodaphlongamine H, and might become a lead compound for further biological study.
Article Details
Authors (16)
Sora Iwamoto
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Reki Nakano
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Keiji Sasaki
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Shoichiro Kobayashi
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Yuki Taira
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Koya Takei
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Reiji Kawakita
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Ayako Tokuyama
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Haruto Nakamura
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Manato Tomoike
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Ryota Kawahara
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Akari Murase
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Siro Simizu
Noritaka Chida
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Toshitaka Okamura
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan
Takaaki Sato
Department of Applied Chemistry Faculty of Science and Technology Keio University 3‐14‐1 Hiyoshi, Kohoku‐ku Yokohama Kanagawa 223–8522 Japan