Stereoselective synthesis of the C1-C16 fragment of the antifungal marine polyether macrolide goniodomin A is described. A Stille-type coupling of organostannanes and thioesters was exploited as the key carbon-carbon bondforming process, namely for the formation of the C7-C8 and C11-C12 bonds. Construction of the spiroacetal domain via acid-catalyzed acetalization of a triol-enone 30 unexpectedly provided a mixture of natural 11S spiroacetal 2, unnatural 11R spiroacetal 32, and constitutional isomer 33. Fortunately, it was eventually found that protection of the C5 hydroxy group as its acetate facilitated the isolation of natural 11S isomer 47 via acid-catalyzed equilibration of unnatural 11R isomer 48 and avoided the formation of a constitutional isomer, thereby increasing the efficacy of the spiroacetalization process.
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