| Abstract
| - A novel total synthesis of the complex polyketide (+)-discodermolide, a promising anticancer agentof sponge origin, has been completed in 7.8% overall yield over 24 linear steps, with 35 stepsaltogether. This second-generation approach was designed to rely solely on substrate control forintroduction of the required stereochemistry, eliminating the use of all chiral reagents or auxiliaries.The common 1,2-anti-2,3-syn stereotriad found in each of three subunits, aldehyde 9 (C1−C5), ester40 (C9−C16), and aldehyde 13 (C17−C24), was established via a boron-mediated aldol reaction ofethyl ketone 15 and formaldehyde, followed by hydroxyl-directed reduction to give 1,3-diol 14.Alternatively, a surrogate aldehyde 22 was employed for formaldehyde in this aldol reaction, leadingto the β-hydroxy aldehyde 20 as a common building block, corresponding to the discodermolidestereotriad. Key fragment unions were achieved by a lithium-mediated anti aldol reaction of ester40 and aldehyde 13 under Felkin−Anh control to provide (16S,17S)-adduct 51 and a boron-mediatedaldol reaction between enone 10 and aldehyde 9, exploiting unprecedented remote 1,6-stereoinduction, to give the (5S)-adduct 57.
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