Late-stage intermolecular CH activation for lead diversification: a highly chemoselective oxyfunctionalization of the C-9 position of potent bryostatin analogues.
Treatment of highly potent and densely functionalized bryostatin analogue 1 with dimethyldioxirane afforded the C-9 hydroxylated hemiketal 2 via oxyfunctionalization of the C9-CH bond, one of 12 CH bonds geminal to an oxygen substituent in 1. When bryostatin analogue 3 was subjected to identical conditions, oxidation of a C-26 secondary hydroxyl group was found to compete with C-9 hydroxylation. Complete selectivity for C-9 hydroxylation was restored upon acylation of the C-26 secondary alcohol.
Wender
Paul A
PA
Department of Chemistry, Stanford University, Stanford, California 94305-8050, USA. wenderp@stanford.edu
Hilinski
Michael K
MK
Mayweg
Alexander V W
AV
D054713:Bryostatins; D006860:Hydrogen Bonding; D006900:Hydroxylation; D018942:Macrolides / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011493:Protein Kinase C / Q000378:metabolism
D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C