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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.

SUBMITTER: Brogan JT

PROVIDER: S-EPMC3254090 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Total Synthesis (+)-7-Bromotrypargine and Unnatural Analogs: Biological Evaluation Uncovers Activity at CNS Targets of Therapeutic Relevance.

Brogan John T JT Stoops Sydney L SL Crews Brenda C BC Marnett Lawrence J LJ Lindsley Craig W CW

ACS chemical neuroscience 20111101 11

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 optimiz ...[more]

PMID: 22247792

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