A stereoselective asymmetric synthesis of antibiotic (-)-fumagillol using claisen rearrangement and intramolecular ester enolate alkylation as key steps.
(-)-Fumagillol (1), a hydrolysis product of fumagillin, has been synthesized by several group from commercially available 1,2:5,6-di-O-isopropylidene-alpha-D-allofuranose in a highly stereoselective manner. Chiral centers on C5 and C6 came from D-allofuranose and the asymmetric center on C4 was accomplished by 1,3-chirality transfer using the Claisen rearrangement on a chiral allyl alcohol. Chirality, which is necessary on an epoxide consisting of the spiro-ring system, was diastereoselectively constructed by the well-known reaction, intramolecular ester enolate alkylation (IEEA), which showed that this reaction can be applied to the alpha-alkoxy ester system. The epoxide on the side chain was regioselectively introduced by the difference between the number of substituents on the vinyl groups. This accomplishment proved that IEEA can be a useful tool for the synthesis of complex molecules.
Kim
Deukjoon
D
College of Pharmacy, Seoul National University, Shinrim-Dong, Kwanak-Ku, Seoul 151-742, South Korea.
Ahn
Soon Kil
SK
Bae
Hoon
H
Kim
Hak Sung
HS
D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D003510:Cyclohexanes; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D012997:Solvents; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D003510:Cyclohexanes; D007202:Indicators and Reagents; D012717:Sesquiterpenes; D012997:Solvents; C057299:fumagillol