Issue 15, 2019

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


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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Article information

Article type
Edge Article
19 Dec 2018
07 Mar 2019
First published
19 Mar 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 4334-4338

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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