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Total Synthesis of cyclo‐Mumbaistatin Analogues through Anionic Homo‐Fries Rearrangement
Author(s) -
Neufeind Stefan,
Hülsken Nils,
Neudörfl JörgMartin,
Schlörer Nils,
Schmalz HansGünther
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201003166
Subject(s) - total synthesis , natural product , stereochemistry , chemistry , moiety , polyketide , cycloaddition , polyene , benzophenone , fries rearrangement , biosynthesis , organic chemistry , catalysis , enzyme
The structurally unique polyketide mumbaistatin is the strongest naturally occurring inhibitor of glucose‐6‐phosphate translocase‐1 (G6P‐T1), which is a promising target for drugs against type‐2 diabetes mellitus and angiogenic processes associated with brain tumor development. Despite its high relevance, mumbaistatin has so far withstood all attempts towards its total synthesis. In the present study an efficient total synthesis of a deoxy‐mumbaistatin analogue containing the complete carbon skeleton and a spirolactone motif closely resembling the natural product in its cyclized form was elaborated. Key steps of the synthesis are a Diels–Alder cycloaddition for the construction of the fully functionalized anthraquinone moiety and an anionic homo‐Fries rearrangement to build up the tetra‐ ortho ‐substituted benzophenone core motif, from which a spiroketal lactone forms in a spontaneous process. The elaborated strategy opens an entry to a variety of new analogs of mumbaistatin and cyclo‐mumbaistatin and may be exploited for the total synthesis of the natural product itself in the future.