Brogan, John T. Stoops, Sydney L. Lindsley, Craig W. Total Synthesis and Biological Evaluation of Phidianidines A and B Uncovers Unique Pharmacological Profiles at CNS Targets The synthesis of phidianidines A and B, the first 1,2,4-oxadiazole-containing alkaloid, from the marine opisthobranch mollusk <i>Phidiana militaris</i> is reported. The synthesis proceeds in six steps from known indole acetic acids in 39.9% (phidianidine A) and 21% (phidianidine B) overall yields from commercially available materials. Biological characterization found that phidianidines A and B are selective inhibitors of DAT (versus SERT and NET) and a selective, potent ligand and partial agonist of the μ opioid receptor (versus δ- and κ-opioid receptors). Moreover, neither phidianidines A and B are cytotoxic, and thus represent an attractive starting point for chemical optimization; therefore, we piloted a number of chemistries and prepared a diverse series of unnatural analogs. synthesis proceeds;chemical optimization;B Uncovers;SERT;indole acetic acids;Biological Evaluation;DAT;μ opioid receptor;marine opisthobranch mollusk Phidiana militaris;Pharmacological Profiles;phidianidine B;CNS TargetsThe synthesis;Total Synthesis;Biological characterization 2012-09-19
    https://acs.figshare.com/articles/journal_contribution/Total_Synthesis_and_Biological_Evaluation_of_Phidianidines_A_and_B_Uncovers_Unique_Pharmacological_Profiles_at_CNS_Targets/2485384
10.1021/cn300064r.s001