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Total Synthesis of Hibarimicinone, a v‐ S rc Tyrosine Kinase Inhibitor Possessing the Pseudo‐Dimer Structure of Tetracycline
Author(s) -
Tatsuta Kuniaki,
Hosokawa Seijiro
Publication year - 2014
Publication title -
the chemical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.61
H-Index - 78
eISSN - 1528-0691
pISSN - 1527-8999
DOI - 10.1002/tcr.201300020
Subject(s) - stereochemistry , total synthesis , stereocenter , dimer , thiolactone , moiety , chemistry , ring (chemistry) , annulation , enantioselective synthesis , biochemistry , catalysis , organic chemistry
The total synthesis of hibarimicinone, a potent v‐ S rc tyrosine kinase inhibitor possessing thirteen stereogenic centers and an axial chirality, has been achieved. The key step to constructing the eight‐ring skeleton was the double M ichael– D ieckmann‐type cyclization ( H auser annulation) using a thiolactone pseudo‐dimer. These synthetic studies indicated the efficiency of the thiolactone‐employed route to synthesize the multiply functionalized polycyclic compounds. The ABCD ‐ring moiety including the bridging ether was constructed by a strategy including oxidation of the C ‐ring hydroquinone and the subsequent transfer of the oxidation stage to the neighboring ring. The atropisomer of hibarimicinone was also synthesized to confirm the structure of the natural product.