title: Divergent Synthesis of Aeruginosins Based on a C(sp(3))-H Activation Strategy.
abstract: A general and scalable access to the aeruginosin family of marine natural products, exhibiting potent inhibitory activity against serine proteases, is reported. This was enabled by the strategic use of two recently implemented Pd-catalyzed C(sp(3))-H activation reactions. The first method allowed us to obtain the common 2-carboxy-6-hydroxyoctahydroindole (Choi) core of the target molecules on a large scale, whereas the second method provided a rapid and divergent access to various hydroxyphenyllactic (Hpla) subunits, including halogenated ones. This unique strategy, together with an optimization of the fragment coupling sequence allowed the synthesis of four aeruginosins, that is, 98A-C and 298A from the chiral pool. Among them, aeruginosin 298A was synthesized on an unprecedentedly large scale. In addition, halogenated aeruginosins 98A and 98C were synthesized for the first time, thanks to a fine-tuning of the final hydrogenation step.
authors.affiliation: Université Claude Bernard Lyon 1, CNRS UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, CPE Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France).
authors.forename: David
authors.initials: D
authors.lastname: Dailler
authors.affiliation: Université Claude Bernard Lyon 1, CNRS UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, CPE Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France).
authors.forename: Grégory
authors.initials: G
authors.lastname: Danoun
authors.affiliation: Université Claude Bernard Lyon 1, CNRS UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, CPE Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France).
authors.forename: Benjamin
authors.initials: B
authors.lastname: Ourri
authors.affiliation: Université Claude Bernard Lyon 1, CNRS UMR 5246, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, CPE Lyon, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France). olivier.baudoin@univ-lyon1.fr.
authors.forename: Olivier
authors.initials: O
authors.lastname: Baudoin
mesh_terms: D001430:Bacteriocins / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D007930:Leucine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry; D057057:Serine Proteases / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: C000605529:2-carboxy-6-hydroxyoctahydroindole; D001430:Bacteriocins; D001688:Biological Products; D007211:Indoles; C419325:aeruginosin 298-A; C012706:aeruginocin; D010165:Palladium; D057057:Serine Proteases; D007930:Leucine
keywords: CH activation; aeruginosin; marine natural products; palladium catalysis; total synthesis