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Total Synthesis Confirms Laetirobin as a Formal Diels–Alder Adduct
Author(s) -
Simon Oliver,
Reux Bastien,
La Clair James J.,
Lear Martin J.
Publication year - 2010
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.200900306
Subject(s) - chemistry , sonogashira coupling , alkyne , stereochemistry , furan , alkene , total synthesis , adduct , annulation , cationic polymerization , organic chemistry , catalysis , palladium
Laetirobin, isolated from a parasitic fungus host–plant relationship, was synthesized in six practical steps with an overall yield of 12 % from commercially available 2,4‐dihydroxyacetophenone. Because the product is a pseudosymmetric tetramer of benzo[ b ]furans, each step of the synthesis was designed to involve tandem operations. Highlights include: 1) the double Sonogashira reaction of a bis(alkyne), 2) the practical copper(I)‐mediated formation of a bis(benzo[ b ]furan), and 3) the biomimetic [4+2] dimerization and unexpected cationic [5+2] annulation of gem ‐diaryl alkene precursors. Preliminary structure–activity relationship data between the isomeric [4+2] and [5+2] tetramers revealed only the natural product to possess promising anticancer potential. Specifically, laetirobin is capable of blocking tumor cell division (mitosis) and invoking programmed cell death (apoptosis).