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Total Synthesis of Amphilectolide, Sandresolide B, Archazolid B and towards Archazolid A and Caribenol A

  • Author(s): Chen, Ingrid T.
  • Advisor(s): Trauner, Dirk
  • Toste, Dean
  • et al.
Abstract

The total synthesis and synthetic efforts toward norditerpene natural products isolated from Pseudopterogorgia elisabethae and macrocyclic polyketides from Archangium gephyra is described. A highly convergent synthesis of archazolid B, uniting three linear subunits, is accomplished using various modern transition-metal catalyzed reactions. A relay ring-closing metathesis is featured for closure of the 24-membered macrocyclic ring. Construction of the carbon skeleton of archazolid A is also described, featuring two robust, scaleable building blocks and their unification. New strategies for the construction and elaboration of a 1,4 skipped diene moiety are established in this synthesis.

The total synthesis of norditerpenes amphilectolide and sandresolide B are also described. A palladium mediated carbonylative coupling is featured en route to the preparation of a key furan building block that can be used to access several norditerpene natural products produced from Pseudoterogorgia elisabethae. This key building block was then elaborated to amphilectolide utilizing a lanthanide catalyzed ring closure and furan oxidation with singlet oxygen. The ring-closure product may also be used to access caribenol B.

The furan building block was also used to construct sandresolide B, where a Myers alkylation overcame steric constraints in this system. An intramolecular Friedel Crafts acylation is used to close a 7-membered ring. These strategies also provide insight to a next generation route toward caribenol A, and the progress toward the initial strategy via Stork-Danheiser ring closure is described.

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