Total Synthesis of (-)- and (+)-Balanol(1).
Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement.
Lampe
John W.
JW
Department of Chemical Research, Sphinx Pharmaceuticals, A Division of Eli Lilly and Company, 4615 University Drive, Durham, North Carolina 27707.
Hughes
Philip F.
PF
Biggers
Christopher K.
CK
Smith
Shelley H.
SH
Hu
Hong
H