Convergent and enantioselective total synthesis of (−)-nalanthalide, a potential Kv1.3 blocking immunosuppressant

• Published in: Tetrahedron letters Vol. 47; no. 19; pp. 3251 - 3255
• Main Authors: Abe, Toshiaki, Iwasaki, Katsuhiko, Inoue, Munenori, Suzuki, Takeyuki, Watanabe, Kazuhiro, Katoh, Tadashi
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 08.05.2006; Elsevier
• Subjects: [2,3]-Wittig rearrangement; Chemistry; Chemistry, Organic; Coupling reaction; Immunosuppressive agent; Kv1.3 Blocker; Nalanthalide; Physical Sciences; Science & Technology; Total synthesis; Nalanthalide; Kv1.3 Blocker; Immunosuppressive agent; [2,3]-Wittig rearrangement; Coupling reaction; Total synthesis; SECONDARY ALCOHOLS; REARRANGEMENT; BLOCKERS; coupling reaction; SESQUICILLIN; immunosuppressive agent; nalanthalide; Kv1.3 blocker; total synthesis; POTASSIUM CHANNEL KV1.3; INHIBITOR
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2006.03.039

The first total synthesis of (−)-nalanthalide ( 1 ), a novel blocker of the voltage-gated potassium channel Kv1.3 from a microorganism, was accomplished in a convergent manner by utilizing coupling reaction of the trans-decalin 5 with 3-lithio-γ-pyrone 4 . The key intermediate 5 was efficiently prepared from the known trans-decalone 7 through a [2,3]-Wittig rearrangement of the stannylmethyl ether 6 to install the stereogenic center at C9 and the exo-methylene function at C8.