title: Convergent assembly of highly potent analogues of bryostatin 1 via pyran annulation: bryostatin look-alikes that mimic phorbol ester function.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East, RM 2020, Salt Lake City, Utah 84112, USA. keck@chem.utah.edu
authors.forename: Gary E
authors.initials: GE
authors.lastname: Keck
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Kraft
authors.forename: Anh P
authors.initials: AP
authors.lastname: Truong
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Carina C
authors.initials: CC
authors.lastname: Sanchez
authors.forename: Noemi
authors.initials: N
authors.lastname: Kedei
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Lewin
authors.forename: Peter M
authors.initials: PM
authors.lastname: Blumberg
mesh_terms: D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D054713:Bryostatins / Q000138:chemical synthesis* / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry*; D013755:Tetradecanoylphorbol Acetate / Q000737:chemistry*
chemical_list: D054713:Bryostatins; D011714:Pyrans; C046785:bryostatin 1; D013755:Tetradecanoylphorbol Acetate