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Total Synthesis of Balanol and Designed Analogues
Author(s) -
Nicolaou K. C.,
Koide Kazunori,
Bunnage Mark E.
Publication year - 1995
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.19950010711
Subject(s) - aldehyde , nucleophile , chemistry , hydrogenolysis , total synthesis , aryl , benzophenone , stereochemistry , combinatorial chemistry , salicylaldehyde , ketone , lithium amide , intramolecular force , enantioselective synthesis , catalysis , organic chemistry , alkyl , schiff base
The total synthesis of balanol, a potent protein kinase C inhibitor isolated from the fungus Verticillium balanoides , is described. The hexahydroazepine fragment was prepared from D‐serine through a sequence of reactions including the diastereoselective allylboration of a derived amino aldehyde and a base‐induced 7‐exo‐tet ring closure as key steps. The benzophenone fragment was secured through the initial coupling of the two functionalised aromatic components through an ester linkage, followed by intramolecular nucleophilic attack of an aryl lithium derivative to form the desired ketone bridge. After coupling of the two balanol domains, the adoption of benzylderived protecting groups for the latent functionalities then allowed the liberation of balanol in a single step by catalytic hydrogenolysis. Finally, the newly developed synthetic strategy was applied to the synthesis of a variety of designed balanol analogues for biological evaluation.