A total synthesis of (±)cerulenin

✍ Scribed by E.J. Corey; David R. Williams

• Publisher: Elsevier Science
• Year: 1977
• Tongue: French
• Weight: 230 KB
• Volume: 18
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)83370-0

✦ Synopsis

The antifungal antibiotic, cerulenin 3 was isolated from the culture filtrate of Cephalosporium caerulens, 1 and shown to inhibit lipid biosynthesis of Escherichia coli by irreversibly binding P-ketoacyl-acyl carrier protein synthetase, the enzyme which catalyzes the acylation of a malonyl thioester for the chain lengthening reaction of fatty acid synthesis. 2 The structure originally proposed 3a for cerulenin on the basis of chemical and spectroscopic data was revised to 1 in 1974 3b on the basis of a detailed nmr study. Very recently two different synthetic routes to the racemic antibiotic have been reported. 4 This communication describes concurrent work in these laboratories which has led to a simple and convergent synthesis of (+)-cerulenin. Treatment of 3-butyn -l-o1 with dihydropyran (1.2 equiv, CH2C12, O", 2 hr) and a catalytic amount of toluenesulfonic acid gave the tetrahydropyranyl ether 2_ (bp 86-90" at 20mm) in 96% yield. Hydrostannation of the terminal acetylene proceeded smoothly with tri-n_butyltin hydride at 90" for 10 hr in the presence of a catalytic amount of the radical initiator, azoisobutyronitrile, affording the vinylstannane 3 which was diluted -