Convergent assembly of highly potent analogues of bryostatin 1 via pyran annulation: bryostatin look-alikes that mimic phorbol ester function.
Highly potent bryostatin analogues which contain the complete bryostatin core structure have been synthesized using a pyran annulation approach as a key strategic element. The A ring pyran was assembled using a pyran annulation reaction between a C1-C8 hydroxy allylsilane and an aldehyde comprising C9-C13. This pyran was transformed to a new hydroxy allylsilane and then coupled with a preformed C ring aldehyde subunit in a second pyran annulation, with concomitant formation of the B ring. This tricyclic intermediate was elaborated to bryostatin analogues which displayed nanomolar to subnanomolar affinity for PKC, but displayed properties indistinguishable from a phorbol ester in a proliferation/attachment assay.
Keck
Gary E
GE
Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, USA. keck@chem.utah.edu
Kraft
Matthew B
MB
Truong
Anh P
AP
Li
Wei
W
Sanchez
Carina C
CC
Kedei
Noemi
N
Lewin
Nancy E
NE
Blumberg
Peter M
PM
D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D054713:Bryostatins / Q000138:chemical synthesis* / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry*
D054713:Bryostatins; D011714:Pyrans; C046785:bryostatin 1; D013755:Tetradecanoylphorbol Acetate