The Total Synthesis of the Bioactive Natural Product Plantazolicin A and Its Biosynthetic Precursor Plantazolicin B.
Herein, we describe our full investigations into the synthesis of the peptide-derived natural product plantazolicin A, a compound that demonstrates promising selective activity against the causative agent of anthrax toxicity, and its biosynthetic precursor plantazolicin B. This report particularly focuses on the challenging preparation of the arginine containing thiazole fragment, including the development of a robust, high yielding procedure that avoids the use of sulfurating agents. Extensive studies on the design of a coherent protecting group strategy and the establishment of a step-efficient dicyclization/oxidation approach allowed high levels of convergence for the construction of the oxazole fragments. This has led to a unified, highly convergent synthesis for both plantazolicin A and B.
Department of Chemistry, University of Cambridge, Lensfield road, CB21EW, Cambridge, UK.|GlaxoSmithKline, Gunnels Wood Rd, SG12NY, Stevenage, UK.
Sabine
S
Fenner
Department of Chemistry, University of Cambridge, Lensfield road, CB21EW, Cambridge, UK.
Zoe E
http://orcid.org/0000-0003-4606-9831
ZE
Wilson
Department of Chemistry, University of Cambridge, Lensfield road, CB21EW, Cambridge, UK. svl1000@cam.ac.uk.
Steven V
http://orcid.org/0000-0002-7816-0042
SV
Ley
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry*; D010084:Oxidation-Reduction; D013844:Thiazoles / Q000737:chemistry*
D001688:Biological Products; D009842:Oligopeptides; D010080:Oxazoles; D013844:Thiazoles; C560834:plantazolicin A; C560835:plantazolicin B
antibiotics; heterocycles; natural products; polyazole; total synthesis