Synthesis of stereopure acyclic 1,5-dimethylalkane chirons: building blocks of highly methyl-branched natural products

An efficient synthetic method towards stereopure acyclic 1,5-dimethylalkane building blocks from methyl (2R)-3-hydroxy-2-methylpropionate (R)-1 (>99% ee) and methyl (2S)-3-hydroxy-2-methylpropionate (S)-1 (>99% ee) through a series of chemical transformations, including Julia–Kocienski olefination and diimide reduction, is described. Through this strategy, two fragments of β-d-mannosyl phosphomycoketide (C₃₂-MPM) and four stereopure 1,5-dimethylalkane C₁₀ chirons are prepared. These C₃₂-MPM fragments and C₁₀ chirons have shown great potential application as building blocks for the synthesis of highly methyl-branched natural products containing chiral oligoisoprenoid-like chains.