A convergent and enantioselective synthesis of the northwestern fragment of tausalarin C, a bismacrolide isolated from the Madagascan sponge, has been achieved. The linear chain (C1-C14) comprising pre-taumycin A consists of three key subunits. The tri-substituted double bond in each subunit was introduced via hydrostannylation and hydrozirconation. The stereochemistry of C4” and C5” were introduced by the Evans asymmetric aldol reaction, and the stereochemistry of C9” was derived from (S)-Roche ester. Palladium catalyzed Suzuki coupling reaction followed by addition of lithium butyl enolate provided the linear chain. After the esterification and amide coupling reaction using EDC and DMAP, the macrocycle was introduced using Maio's protocol. |
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