Synthetic transformation of ptychantin into forskolin and 1,9-dideoxyforskolin.
Forskolin (1), a highly oxygenated labdane diterpenoid and an activator of adenylate cyclase, has been synthesized in 12 steps and 12% overall yield from ptychantin A (4), which has been isolated from liverwort Ptychanthus striatus in good yield. The 1alpha-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium in t-BuOH. The 9alpha-hydroxy group was introduced stereoselectively by epoxidation of delta(9.11)-enolether. 1,9-Dideoxyforskolin (2), an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. The hydroxy group at C-1 was removed by solid-state thicarbonylimidazolation and subsequent radical cleavage.
Hagiwara
Hisahiro
H
Graduate School of Science and Technology, Niigata University, 8050, 2-Nocho, Ikarashi, Niigata 950-2181, Japan. hagiwara@gs.niigata-u.ac.jp
Takeuchi
Fumihide
F
Kudou
Masaru
M
Hoshi
Takashi
T
Suzuki
Toshio
T
Hashimoto
Toshihiro
T
Asakawa
Yoshinori
Y
D000262:Adenylyl Cyclases / Q000187:drug effects; D005576:Colforsin / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D004224:Diterpenes / Q000138:chemical synthesis; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors
D004224:Diterpenes; D051246:Glucose Transport Proteins, Facilitative; D005576:Colforsin; D000262:Adenylyl Cyclases; C047983:1,9-dideoxyforskolin