Furan oxidation applied to the synthesis of salinomycin

Brown, Richard Charles Downie (1994) Furan oxidation applied to the synthesis of salinomycin. University of Southampton, Doctoral Thesis.

Abstract

The synthesis of the polyether antibiotic salinomycin 1.01 was achieved by a convergent route from three fragments aldehyde 1.09, furan 4.32 and lactone 2.12.

The aldehyde 1.09 was prepared in 28% yield over eight steps by degradation of salinomycin 1.01 using a known retro-aldol reaction. The central fragment 4.32 was prepared by a stereoconvergent route in about 15% yield over 17 or 19 steps from readily available starting materials. The right fragment 2.12 was synthesised in 2% yield over 22 steps from neryl acetate.

Coupling of the central 4.32 and right 2.12 fragments gave a 2,5 disubstituted furan which upon oxidative rearrangement gave two diastereoisomeric dispiroacetals in a ratio of three to one. The major dispiroacetal 7.05 was converted to salinomycin 1.01.

Notable achievements include: the highly efficient and stereoselective large scale preparation of the central fragment 4.32. The use of asymmetric permanganate promoted oxidative cyclisation of a 1,5-diene to introduce all of the stereochemical information required for the synthesis of the right fragment 2.12 in a single reaction. The use of the furan nucleus in the key fragment linking reaction and in the generation of highly substituted dispiroacetals. vskip 3.0cm

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