A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural product amphidinol 3 is reported. A common intermediate was synthesized from D-tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing metathesis sequence to construct the THP rings. Differential elaboration of the common intermediate allowed the synthesis of two distinct coupling partners, which were joined through a modified Horner-Wadsworth-Emmons olefination to provide the bis-tetrahydropyran core. A convergent approach to the C9-C29 fragment has also been achieved, utilizing Julia-Kocienski olefination to unite key fragments. Exploiting the repeating units of the C1-C17 domain of the polyol, stereocenters C2, C6, C10, and C14 have all been introduced via the asymmetric glycolate alkylation reaction. An iterative acetate aldol sequence followed by a propionate aldol provided the carbon skeleton and required stereocenters of the C21-C29 domain. Following completion of the polyol domain, union with the bis-tetrahydropyran core is envisioned to introduce the C1-C52 domain of amphidinol 3.
|Advisor:||Crimmins, Michael T.|
|Commitee:||Brookhart, Maurice S., Gagne, Michel R., Templeton, Joseph L., Waters, Marcey L.|
|School:||The University of North Carolina at Chapel Hill|
|School Location:||United States -- North Carolina|
|Source:||DAI-B 73/01, Dissertation Abstracts International|
|Keywords:||Amphidinol 3, Natural products, Total synthesis|
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