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First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin
Author(s) -
Neumeyer Markus,
Brückner Reinhard
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201611183
Subject(s) - actinorhodin , steric effects , chemistry , moiety , total synthesis , stereoselectivity , stereochemistry , dihydroxylation , sharpless asymmetric dihydroxylation , halogenation , substituent , enantioselective synthesis , organic chemistry , polyketide , catalysis , biosynthesis , enzyme
Abstract We have accomplished the first total synthesis of an isomerically pure naphthoquinonopyrano‐γ‐lactone dimer, γ‐actinorhodin, in eleven steps. Two steps exploit pairs of peri‐MeO groups as unusual selectivity controls. The respective MeO groups convey the steric bulk of a bromo or iodo substituent located ortho to one MeO group as steric hindrance into the vicinity of the second MeO group. This relay effect was indispensable for exerting regiocontrol in an aromatic bromination and diastereocontrol in an oxa‐Pictet–Spengler cyclization. The absolute configuration of our target compound was established in an asymmetric Sharpless dihydroxylation of a β,γ‐unsaturated ester, which was synthesized in a Heck coupling of a bromoiodonaphthalene with ethyl vinylacetate. The dihydroxylation provided the γ‐hydroxylactone moiety of the bromonaphthalene that was used as the substrate in the oxa‐Pictet–Spengler cyclization. Dimerization to the core of γ‐actinorhodin occurred by two Suzuki couplings.