Abstract
Herein, we report the synthesis of novel ring-expanded bryostatin analogues. By carefully modifying the substrate, a selective and high-yielding Ru-catalyzed tandem enyne coupling/Michael addition was employed to construct the northern fragment. Ring-closing metathesis was utilized to form the 31-membered ring macrocycle of the analogue. These ring-expanded bryostatin analogues possess anticancer activity against several cancer cell lines. Given the difficulty in forming the C16-C17 olefin at a late stage, we also describe our development of a new-generation strategy to access the C7-C27 fragment, containing both the ring B and C subunits.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemical synthesis*
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Bryostatins / chemical synthesis*
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Bryostatins / chemistry*
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Bryostatins / pharmacology
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Catalysis
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Cell Line, Tumor
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Cyclization
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Cycloparaffins / chemistry*
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Humans
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Macrolides / chemical synthesis*
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Macrolides / chemistry*
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Macrolides / pharmacology
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Magnetic Resonance Spectroscopy
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Molecular Structure
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Palladium / chemistry*
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Ruthenium / chemistry*
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Stereoisomerism
Substances
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Antineoplastic Agents
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Bryostatins
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Cycloparaffins
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Macrolides
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Palladium
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Ruthenium