title: Stereoselective synthesis of trifluoro- and monofluoro-analogues of frontalin and evaluation of their biological activity.
abstract: The stereoselective synthesis of both enantiomers of trifluoro frontalin (-)-(1S,5R)- and (+)-(1R,5S)-8, as well as of diastereomeric monofluoro frontalines (-)-(1R,2R,5R)-18 and (-)-(1R,2S,5R)-20, analogues of the bioactive component of the aggregation pheromone of the Scolytidae insect family, has been accomplished starting from (-)-(1R)- and (+)-(1S)-menthyl (S)-toluene-4-sulfinate as a source of chirality and methyl trifluoroacetate or fluoroacetate, respectively, as sources of fluorine. The C-1 stereocenters were installed via stereoselective epoxidation of beta-sulfinyl ketones 2 and 13 with diazomethane. The bicyclic core was obtained by totally stereocontrolled and chemoselective tandem Wacker oxidation/intramolecular ketalization of the intermediate unsatured sulfinyl diols 5, 15, and 19. Axially fluorinated (-)-20 elicited a strong electroantennographic response in laboratory tests on females of Dendroctonus micans, whereas equatorially fluorinated (-)-18 and the trifluoroanalogue (-)-8 showed modest responses. Field trials using (-)-20 were not indicative owing to the locally scarce population of D. micans, but it showed some attractiveness for other Coleoptera families.
authors.affiliation: CNR, Centro di Studio sulle Sostanze Organiche Naturali, via Mancinelli 7, I-20131 Milano, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Ambrosi
authors.forename: A
authors.initials: A
authors.lastname: Arnone
authors.forename: P
authors.initials: P
authors.lastname: Bravo
authors.forename: L
authors.initials: L
authors.lastname: Bruché
authors.forename: A
authors.initials: A
authors.lastname: De Cristofaro
authors.forename: V
authors.initials: V
authors.lastname: Francardi
authors.forename: M
authors.initials: M
authors.lastname: Frigerio
authors.forename: E
authors.initials: E
authors.lastname: Gatti
authors.forename: G S
authors.initials: GS
authors.lastname: Germinara
authors.forename: W
authors.initials: W
authors.lastname: Panzeri
authors.forename: F
authors.initials: F
authors.lastname: Pennacchio
authors.forename: C
authors.initials: C
authors.lastname: Pesenti
authors.forename: G
authors.initials: G
authors.lastname: Rotundo
authors.forename: P F
authors.initials: PF
authors.lastname: Roversi
authors.forename: C
authors.initials: C
authors.lastname: Salvadori
authors.forename: F
authors.initials: F
authors.lastname: Viani
authors.forename: M
authors.initials: M
authors.lastname: Zanda
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D001517:Coleoptera; D004594:Electrophysiology; D005260:Female; D005461:Fluorine; D007202:Indicators and Reagents; D007300:Insect Control; D010675:Pheromones / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012679:Sense Organs; D013237:Stereoisomerism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D007202:Indicators and Reagents; D010675:Pheromones; D005461:Fluorine; C012327:frontalin