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 cente rs of diethyl L-tartrate. The starting diethyl L-tartrate was converted int o trans-2-ethynyl-3-hydroxytetrahydropyran 14 in a stereoselective manner v ia the endo mode cyclization of the epoxy-alkyne derivative 12. The alcohol 12 was then transformed into (E)-iodoolefin derivative 15, which was expos ed to a coupling reaction with 1-tributylstannyl-1,3,5-heptyne (19), derive d from the corresponding 1-trimethylsilyl-1,3,5-heptyne (18), under Stille conditions to produce the all-carbon framework of the target natural produc ts. Chemical modification of the coupled product 20 under conventional cond itions completed the first total synthesis of (-)-ichthyothereol (1) and it s acetate ((+)-2).