title: Synthesis of (+)-7,20-Diisocyanoadociane and Liver-Stage Antiplasmodial Activity of the Isocyanoterpene Class.
abstract: 7,20-Diisocyanoadociane, a scarce marine metabolite with potent antimalarial activity, was synthesized as a single enantiomer in 13 steps from simple building blocks (17 linear steps). Chemical synthesis enabled identification of isocyanoterpene antiplasmodial activity against liver-stage parasites, which suggested that inhibition of heme detoxification does not exclusively underlie the mechanism of action of this class.
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Lu
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Pronin
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine , 9500 Gilman Drive 0741, La Jolla, California 92093, United States.
authors.forename: Yevgeniya
authors.initials: Y
authors.lastname: Antonova-Koch
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine , 9500 Gilman Drive 0741, La Jolla, California 92093, United States.
authors.forename: Stephan
authors.initials: S
authors.lastname: Meister
authors.affiliation: Department of Pediatrics, University of California, San Diego, School of Medicine , 9500 Gilman Drive 0741, La Jolla, California 92093, United States.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Winzeler
authors.affiliation: Department of Chemistry, The Scripps Research Institute , 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Shenvi
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006418:Heme / Q000378:metabolism; D008099:Liver / Q000469:parasitology*; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects*; D011721:Pyrenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000962:Antimalarials; D009570:Nitriles; D011721:Pyrenes; D006418:Heme; C424431:diisocyanoadociane