title: Two rare-class tricyclic diterpenes with antitubercular activity from the Caribbean sponge Svenzea flava. Application of vibrational circular dichroism spectroscopy for determining absolute configuration.
abstract: Two new natural products, 3 and 4, and their predecessor 7-isocyanoisoneoamphilecta-1(14),15-diene (2), of the rare isoneoamphilectane class of marine diterpenes, along with the known amphilectane diterpenes 6-8, were isolated from the n-hexane extract of the marine sponge Svenzea flava collected at Great Inagua Island, Bahamas. The molecular structures of compounds 3 and 4 were established by spectroscopic (1D/2D NMR, IR, UV, HRMS) methods and confirmed by a series of chemical correlation studies. In a first ever case study of the assignment of the absolute configuration of a molecule based on the isoneoamphilectane carbon skeleton, the absolute configuration of compound 5 was established as 3S,4R,7S,8S,11R,12S,13R by application of vibrational circular dichroism (VCD). In vitro anti-TB screenings revealed that metabolites 2-4 and, in particular, semisynthetic analogue 5, are strong growth inhibitors of Mycobacterium tuberculosis H37Rv.
authors.affiliation: Department of Chemistry, University of Puerto Rico , P.O. Box 23346, U.P.R. Station, San Juan, Puerto Rico 00931-3346.
authors.forename: Edward
authors.initials: E
authors.lastname: Avilés
authors.forename: Abimael D
authors.initials: AD
authors.lastname: Rodríguez
authors.forename: Jan
authors.initials: J
authors.lastname: Vicente
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002942:Circular Dichroism; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011161:Porifera / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014732:Vibration
chemical_list: D000995:Antitubercular Agents; D001688:Biological Products; D004224:Diterpenes