title: Total synthesis of clavatadine A.
abstract: The first total synthesis of the potent and selective human blood coagulation factor XIa inhibitor clavatadine A (1) is described. Direct, early-stage guanidinylation enabled rapid, convergent access to an immediate clavatadine A precursor. Concomitant lactone hydrolysis and guanidine deprotection with aqueous acid cleanly provided clavatadine A (1) in only four steps (longest linear sequence, 41-43% overall yield).
authors.affiliation: Department of Chemistry, Central Washington University , 400 East University Way, Ellensburg, Washington 98926-7539, United States.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Conn
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Vreeland
authors.forename: Alexandra N
authors.initials: AN
authors.lastname: Wexler
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Pouwer
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Pouwer
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.forename: Stephen
authors.initials: S
authors.lastname: Chamberland
mesh_terms: D000818:Animals; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011161:Porifera / Q000737:chemistry
chemical_list: D006146:Guanidines; D007783:Lactones; D010648:Phenylacetates; C531075:clavatadine A; D015945:Factor XIa