title: Total Synthesis of Microcystin-LF and Derivatives Thereof.
abstract: Microcystins (MCs) are highly toxic natural products which are produced by cyanobacteria. They can be released to the water during harmful algal blooms and are a serious threat to animals and humans. Described is the total synthesis of the cyanotoxin microcystin-LF (MC-LF, 1a) and two derivatives thereof. Deuterated derivative 1b is of interest as an internal standard during MC quantification in biological samples by mass spectrometry and alkyne-labeled 1c can be employed for toxin derivatization by click chemistry with an azide-containing reporter molecule or as an activity-based probe to identify interaction partners. Application of tert-butyl ester protecting groups for erythro-β-d-methylaspartic acid and γ-d-glutamic acid were key for an isomerization-free synthesis. The analytical data of synthetic MC-LF were identical to those of an authentic sample of the natural product. All derivatives 1a-c were determined to be potent inhibitors of protein phosphatase-1 with similar activity.
authors.affiliation: Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zemskov
authors.affiliation: Department of Biology and Graduate School Biological Sciences (GBS), University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Altaner
authors.affiliation: Department of Biology and Graduate School Biological Sciences (GBS), University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Dietrich
authors.affiliation: Department of Chemistry and Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Valentin
authors.identifier: 0000-0003-4043-6813
authors.initials: V
authors.lastname: Wittmann
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003500:Cyclization; D006801:Humans; D013058:Mass Spectrometry; D052998:Microcystins / Q000138:chemical synthesis*; D013057:Spectrum Analysis
chemical_list: D052998:Microcystins; C524165:microcystin-LF