First total synthesis of (-)-ichthyothereol and its acetate.
The first and stereoselective total syntheses of (-)-ichthyothereol (1) and its acetate ((+)-2) were achieved by incorporation of the two chiral centers of diethyl L-tartrate. The starting diethyl L-tartrate was converted into trans-2-ethynyl-3-hydroxytetrahydropyran 14 in a stereoselective manner via the endo mode cyclization of the epoxy-alkyne derivative 12. The alcohol 12 was then transformed into (E)-iodoolefin derivative 15, which was exposed to a coupling reaction with 1-tributylstannyl-1,3,5-heptyne (19), derived from the corresponding 1-trimethylsilyl-1,3,5-heptyne (18), under Stille conditions to produce the all-carbon framework of the target natural products. Chemical modification of the coupled product 20 under conventional conditions completed the first total synthesis of (-)-ichthyothereol (1) and its acetate ((+)-2).
Mukai
C
C
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi 13-1, Kanazawa 920-0934, Japan. cmukai@kenroku.kanazawa-u.ac.jp
Miyakoshi
N
N
Hanaoka
M
M
D000480:Alkynes; D010946:Plants, Medicinal / Q000737:chemistry; D053279:Polyynes; D011714:Pyrans / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013644:Tartrates / Q000737:chemistry
D000480:Alkynes; D011714:Pyrans; D013644:Tartrates; C008102:ichthyothereol; D053279:Polyynes; C029768:tartaric acid