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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.

SUBMITTER: Keck GE

PROVIDER: S-EPMC2516406 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Convergent assembly of highly potent analogues of bryostatin 1 via pyran annulation: bryostatin look-alikes that mimic phorbol ester function.

Keck Gary E GE 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

Journal of the American Chemical Society 20080502 21

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 t ...[more]

PMID: 18452293

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Synthetic Studies Toward Bryostatin 1: Preparation of a C(1)-C(16) Fragment by Pyran Annulation.

Project description:An expeditious assembly of a C(1)-C(16) subunit of bryostatin 1 is described. A pyran annulation reaction was utilized to form the B-ring by reaction of a hydroxy-allylsilane with a fully elaborated A-ring subunit. This annulation process proceeded with complete diastereoselectivity and in excellent isolated yield despite the presence of potentially sensitive functionality in the A-ring segment.

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Comparison of transcriptional response to phorbol ester, bryostatin 1, and bryostatin analogs in LNCaP and U937 cancer cell lines provides insight into their differential mechanism of action.

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Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis.

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Greater transiency in modulation of gene expression is the predominant difference between the actions of bryostatin 1 and phorbol ester in LNCaP and U937 cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-12-30 | GSE104377 | GEO

Phorbol ester enhances KAI1 transcription by recruiting Tip60/Pontin complexes.

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