title: Total Synthesis (+)-7-Bromotrypargine and Unnatural Analogs: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance.
abstract: The first total synthesis of (+)-7-bromotrypargine, a β-carboline alkaloid from Ancornia sp. is reported. The synthesis proceeds in 9 steps, 8 steps longest linear sequence, in 36.9% overall yield. Biological characterization found that (+)-7-bromotrypargine is an H(3) antagonist, and a selective inhibitor of DAT and NET, without inhibiting SERT. Moreover, unlike electron rich congeners, (+)-7-bromotrypargine is not cytotoxic, and thus represents an attractive starting point for chemical optimization; therefore, we piloted a number of chemistries for the synthesis of unnatural analogs.
authors.affiliation: Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
authors.forename: John T
authors.initials: JT
authors.lastname: Brogan
authors.forename: Sydney L
authors.initials: SL
authors.lastname: Stoops
authors.forename: Brenda C
authors.initials: BC
authors.lastname: Crews
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley