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Issue 15, 2019
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Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

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Abstract

Pyruvic acid and other α-keto acids are frequently encountered as intermediates in metabolic pathways, yet their application in total synthesis has met with limited success. In this work, we present a bioinspired strategy that utilizes highly functionalized OBO (oxabicyclo[2.2.2]octyl) orthoester masked α-ketoacids as key intermediates for the construction of both type I and II lamellarin alkaloids. Lamellarin D was synthesized, via a key 1,4-dicarbonyl, in 7 steps and 22% yield from pyruvic acid. Key steps in the synthesis involve one-pot double enolate functionalisation of 1 followed by double annulation to form the target pyrrole/N-vinyl pyrrole core and late-stage direct C–H arylation. Lastly, a novel OBO-masked β-cyano ketone, synthesized from 1, proved to be a valuable intermediate for construction of the type II lamellarin core via HBr-mediated cyclisation. In this way, lamellarin Q was synthesized in 7 steps and 20% yield from pyruvic acid.

Graphical abstract: Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

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Publication details

The article was received on 19 Dec 2018, accepted on 07 Mar 2019 and first published on 19 Mar 2019


Article type: Edge Article
DOI: 10.1039/C8SC05678A
Chem. Sci., 2019,10, 4334-4338
  • Open access: Creative Commons BY license
    All publication charges for this article have been paid for by the Royal Society of Chemistry

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    Synthesis of lamellarin alkaloids using orthoester-masked α-keto acids

    H. J. Shirley, M. Koyioni, F. Muncan and T. J. Donohoe, Chem. Sci., 2019, 10, 4334
    DOI: 10.1039/C8SC05678A

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