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Total synthesis of biseokeaniamides A-C and late-stage electrochemically-enabled peptide analogue synthesis.

ABSTRACT: The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A-C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation-nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated N,O-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. The value of this late-stage modification method is highlighted by the expedient and divergent production of bioactive peptide analogues, including compounds which exhibit enhanced cytotoxicity relative to the biseokeaniamide natural products.

SUBMITTER: Lin Y

PROVIDER: S-EPMC8162360 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Total synthesis of biseokeaniamides A-C and late-stage electrochemically-enabled peptide analogue synthesis.

Lin Yutong Y Malins Lara R LR

Chemical science 20200730 39

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A-C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation-nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for bu ...[more]

PMID: 34094328

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