title: Total synthesis and biological evaluation of transvalencin Z.
abstract: The emerging global epidemic of drug-resistant tuberculosis has created an urgent need to identify novel therapeutic approaches for disease treatment. Transvalencin Z (1) is a natural product from Nocardia transvalensis with relatively potent and selective antimycobacterial activity against Mycobacterium smegmatis, making it an attractive target for structure-activity and mechanism of action studies. The total synthesis of the four possible diastereomers of transvalencin Z was completed (1a-d), and the absolute configurations were defined using chemical synthesis, HPLC retention times, and optical rotation measurements. Surprisingly, none of the transvalencin Z diastereomers exhibited any inhibitory activity against a panel of microbial pathogens, including several species of mycobacteria.
authors.affiliation: Center for Drug Design, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: Kathryn M
authors.initials: KM
authors.lastname: Nelson
authors.forename: Christine E
authors.initials: CE
authors.lastname: Salomon
authors.forename: Courtney C
authors.initials: CC
authors.lastname: Aldrich
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects; D009615:Nocardia / Q000737:chemistry; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012459:Salicylates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010080:Oxazoles; D012459:Salicylates; C513066:transvalencin Z