Abstract
The total synthesis of fully functionalized polyhydroxyamide B,C- seco-analogues of the anticancer compound pancratistatin (PST) ( 1) is reported. Key steps include an Evans' MgCl 2-promoted anti-aldol reaction between a functionalized l-threose derivative and ( R)-(+)-oxazolidinone to stereoselectively form the C-1/C-10b bond and a regiospecific radical-mediated oxidative fragmentation of a 1,3-benzylidene. The B,C- seco compounds 25 and 26 exhibited low activity (ED 50 > 30 microg/mL) for inducing apoptosis in human cancer cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amaryllidaceae Alkaloids* / chemical synthesis
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Amaryllidaceae Alkaloids* / chemistry
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Amaryllidaceae Alkaloids* / pharmacology
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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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Apoptosis / drug effects
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Drug Screening Assays, Antitumor
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Humans
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Isoquinolines* / chemical synthesis
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Isoquinolines* / chemistry
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Isoquinolines* / pharmacology
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Molecular Conformation
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Molecular Structure
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Stereoisomerism
Substances
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Amaryllidaceae Alkaloids
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Antineoplastic Agents
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Isoquinolines
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pancratistatin