Catalytic Z-Selective Cross-Metathesis in Complex Molecule Synthesis: A Convergent Stereoselective Route to Disorazole C[subscript 1]

• Main Authors: Speed, Alexander W. H. (Author), Mann, Tyler J. (Author), O'Brien, Robert V. (Author), Schrock, Richard Royce (Contributor), Hoveyda, Amir H. (Author)
• Other Authors: Massachusetts Institute of Technology. Department of Chemistry (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2016-08-25T16:02:08Z.
• Subjects: Article
• Online Access: Get fulltext

A convergent diastereo- and enantioselective total synthesis of anticancer and antifungal macrocyclic natural product disorazole C1 is reported. The central feature of the successful route is the application of catalytic Z-selective cross-metathesis (CM). Specifically, we illustrate that catalyst-controlled stereoselective CM can be performed to afford structurally complex Z-alkenyl-B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high selectivity (pin = pinacolato). The resulting intermediates are then joined in a single-step operation through catalytic inter- and intramolecular cross-coupling to furnish the desired 30-membered ring macrocycle containing the critical (Z,Z,E)-triene moieties.
National Institutes of Health (U.S.) (NIH (GM-59426)