We report a flexible stereocontrolled synthetic route to the southern fragment of
lagunamides D and D′, two cytotoxic cyclodepsipeptides of the aurilide family. Key
steps in the route include an anti-aldol Abiko–Masamune reaction and a Horner–Wadsworth–Emmons (HWE) olefination. The
key element of our synthetic strategy was the use of a pivotal intermediate which
allows the introduction a side chain that differentiates the polyketide structure
of the members of the family. Thus, to illustrate the synthetic potential of our strategy,
we have also prepared four different advanced polyketide precursors.
Key words
cytotoxicity - macrocycles - aldol reaction - chiral auxiliaries - asymmetric synthesis
