The synthesis of bis-spiroacetal (15) bearing an hydroxymethyl group at c-2 is described establishing a methodology for preparation of the polyether antibiotics salinomycin and narasin.
Formation of an important iodohydrin intermediate has been accomplished by a highly efficient reaction of an epoxide with LiI catalysed by BF3.Et20 in THF. Displacement of the resulting neopentyl iodide was achieved in high yield by reaction of the iodide with potassium superoxide in dimethylsulphoxide/tetrahydrofuran in the presence of 18-crown-6. The 1,6,6-trioxadispiro[4.1.5.3]pentadec-13-ene ring system is a key structural feature of the polyether antibiotics salinomycin and narasinl, and has therefore attracted the attention of synthetic chemists. Whilst Kishi et aI* and Yonemitsu et al3 have focused on the use of a thermodynamically controlled intramolecular ketalization to establish the tricyclic bis-spiroacetal ring system, Albizati and Perron and Kocienski et al5 have made elegant use of an oxidationrearrangement of a 2-fury1 ketone to construct the required bis-spiroacetal system.
1 Scheme
We have previously reported6 the synthesis of the model bis-spiroacetal
(2) containing this same ring system via an oxidative cyclisation of hydroxyspiroacetal
(1) (Scheme 1) using iodobenzene diacetate and iodine under photolytic conditions. We now wish to report our methodology to introduce a suitable functional group, CH2X, at C-2 which provides a handle for further elaboration of the right hand side of this molecule. The group X must be such that it does not stablize a free radical as this may result in C-C bond cleavage to generate the methyl ketone (3) rather than 1,5hydrogen abstraction to generate the required ring system. *MB (3) Rf values. This is a consequence of the ability of the hydroxyl group in the favoured conformation of isomer (15b) to participate in intramolecular hydrogen bonding to the oxygen atom of the neighbouring spiroacetal ring (Figure). Similar hydrogen bonding is not possible in the other isomer (Isa).