Chemistry of bis-spiroacetals: synthesis of cis- and trans-1-(2-methyl-1,6,8-trioxadispiro[4.1.5.3]pentadec-13-en-2-yl)methanol

The synthesis of the cis and trans isomers of the bis-spiroacetal 25 is described, establishing methodology for the preparation of the polyether antibiotic epi-17-deoxy-(O-8)-salinomycin 3. The hydroxymethyl group at C-2 of 25, which provides an important ‘handle’ for elaboration of the right hand side of the molecule, was introduced by SN2 displacement of the hindered iodide 24 using potassium superoxide in dimethyl sulphoxide (DMSO) in the presence of 18-crown-6. Barton-type cyclization of the iodohydrin 10 provided the iodo-bis-spiroacetal 24 with the trans isomers 24a,24b favoured over the cis isomers 24c, 24d by 3:1. The key iodohydrin 10 was prepared in high yield by reaction of the epoxide 9 with Lil catalysed by BF3·Et2O. The epoxide 9, in turn, was prepared by condensation of the highly functionalised acetylene 6, derived from lactonic acid 11, with δ-valerolactone.