Role of the A-ring of bryostatin analogues in PKC binding: synthesis and initial biological evaluation of new A-ring-modified bryologs.
The syntheses of three newly designed bryostatin analogues are reported. These simplified analogues, which lack the A-ring present in the natural product but possess differing groups at C9, were obtained using a divergent approach from a common intermediate. All three analogues exhibit potent, single-digit nanomolar affinity to protein kinase C.
Wender
Paul A
PA
Department of Chemistry, Stanford University, California 94305-5080, USA. wenderp@stanford.edu
Clarke
Michael O
MO
Horan
Joshua C
JC
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D054713:Bryostatins; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D011493:Protein Kinase C / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D011493:Protein Kinase C