Enantioselective total synthesis of (-)-candelalide A, a novel blocker of the voltage-gated potassium channel Kv1.3 for an immunosuppressive agent.
A convergent route to (-)-candelalide A involved the union of a trans-decalin portion (AB ring) and a gamma-pyrone moiety through the C16-C3' bond to assemble the whole carbon framework and subsequent formation of the dihydropyran ring (C ring) as the crucial steps. A strategic [2,3]-Wittig rearrangement was employed for establishing the stereogenic center at C9 and an exo-methylene function at C8 present in the decalin portion. [reaction: see text]
Watanabe
Kazuhiro
K
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan.
Iwasaki
Katsuhiko
K
Abe
Toshiaki
T
Inoue
Munenori
M
Ohkubo
Kôichi
K
Suzuki
Takeyuki
T
Katoh
Tadashi
T
D001203:Ascomycota / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
D004224:Diterpenes; D007166:Immunosuppressive Agents; D051664:Kv1.3 Potassium Channel; D011753:Pyrones; C431986:candelalide A