Synthesis of the novel 1,7,9-trioxadispiro[4.1.5.2]-tetradecane ring system present in the spirolides

摘要

A synthesis of bis-spiroacetal 13 which constitutes the bis-spiroacetal moiety of the complex marine biotoxins,spirolides 1 and 2 is described.The synthetic strategy adopted is based on assembly of a suitable protected acyclic hydroxyketone precursor.Key intermediate 25 was synthesised as a mixture of diastereomers from 1,3-propanediol using an iterative Grignard addition/hydrboration strategy and converted to cis-enone 28.Attempted acid catalysed cyclisation of 28 to a spiroacetal was unsuccessful,however,the analagous saturated precursor 30 readily afforded spiroacetal 31.Oxidative cyclisation of 31 then gave bis-spiroacetal 32.In an altermative route,bis-spiroacetal 32 was synthesised by selective deprotection of diketone 34.Selective deprotection of acetylene 25 gave methoxyl acetal 36 which formed unsaturated spiroacetal 37 upon semi-hydrogenation.Finally,oxidative cyclisation of bis-spiroacetal 37 afforded the target bis-spiroacetal 13.