The first total synthesis of (-)-5-deoxyenterocin has been accomplished starting from pentane-1,3,5-triol (16 steps in the longest linear sequence, 0.2 % overall yield). (-)-Menthone served as the source of chirality to distinguish the enantiotopic hydroxymethyl groups of the substrate. Key steps of the synthesis include two aldol reactions to either end of the C5 -skeleton, a diastereoselective hydroxylation reaction and a biomimetic twofold intramolecular aldol reaction as the final step. Although this step suffered from geometrical constraints and was low yielding (10 %), enough synthetic material could be secured to substantiate the relative and absolute configuration of the natural product. Additional experiments were directed toward a C-H functionalization at carbon atom C5. Despite the fact that several protocols could be successfully applied to (3aR)-(+)-sclareolide as model substrate, (-)-5-deoxyenterocin withstood any selective functionalization.
Keywords: C−H activation; aldol reactions; biomimetic synthesis; polyketides; total synthesis.
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.