title: Biomimetic kinetic resolution: highly enantio- and diastereoselective transfer hydrogenation of aglain ketones to access flavagline natural products.
abstract: We have previously reported asymmetric syntheses and absolute configuration assignments of the aglains (+)-ponapensin and (+)-elliptifoline and proposed a biosynthetic kinetic resolution process to produce enantiomeric rocaglamides and aglains. Herein, we report a biomimetic approach for the synthesis of enantiomerically enriched aglains and rocaglamides via kinetic resolution of a bridged ketone utilizing enantioselective transfer hydrogenation. The methodology has been employed to synthesize and confirm the absolute stereochemistries of the pyrimidone rocaglamides (+)-aglaiastatin and (-)-aglaroxin C. Additionally, the enantiomers and racemate of each metabolite were assayed for inhibition of the heat-shock response, cytotoxicity, and translation inhibition.
authors.affiliation: Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University , Boston, Massachusetts 02215, United States.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Stone
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Lajkiewicz
authors.forename: Luke
authors.initials: L
authors.lastname: Whitesell
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hilmy
authors.forename: John A
authors.initials: JA
authors.lastname: Porco
mesh_terms: D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D007659:Ketones / Q000737:chemistry*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism
chemical_list: D001572:Benzofurans; D001688:Biological Products; D006575:Heterocyclic Compounds, 3-Ring; D007659:Ketones; D011758:Pyrroles; C428176:elliptifoline; C518999:ponapensin; C107772:rocaglamide