Synthesis of antimicrobial natural products targeting FtsZ: (+)-totarol and related totarane diterpenes.
An efficient, convergent synthesis of totarol by a diastereoselective epoxide/alkene/arene bicyclization is described. The reported synthesis enables the preparation of related diterpenes totaradiol and totarolone as well as previously unavailable derivatives that exhibit comparable inhibition of the bacterial cell division protein FtsZ.
Kim
Michelle B
MB
Department of Chemistry, One Shields Ave, University of California, Davis, California 95616, USA.
Shaw
Jared T
JT
D045784:Abietanes; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013237:Stereoisomerism
D045784:Abietanes; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001688:Biological Products; D003598:Cytoskeletal Proteins; D004224:Diterpenes; C071525:FtsZ protein, Bacteria; C553071:totaradiol; C553070:totarolone; C078548:totarol