Issue 34, 2021

‘Reverse biomimetic’ synthesis of l-arogenate and its stabilized analogues from l-tyrosine


L-Arogenate (also known as L-pretyrosine) is a primary metabolite on a branch of the shikimate biosynthetic pathway to aromatic amino acids. It plays a key role in the synthesis of plant secondary metabolites including alkaloids and the phenylpropanoids that are the key to carbon fixation. Yet understanding the control of arogenate metabolism has been hampered by its extreme instability and the lack of a versatile synthetic route to arogenate and its analogues. We now report a practical synthesis of L-arogenate in seven steps from O-benzyl L-tyrosine methyl ester in an overall yield of 20%. The synthetic route also delivers the fungal metabolite spiroarogenate, as well as a range of stable saturated and substituted analogues of arogenate. The key step in the synthesis is a carboxylative dearomatization by intramolecular electrophilic capture of tyrosine's phenolic ring using an N-chloroformylimidazolidinone moiety, generating a versatile, functionalizable spirodienone intermediate.

Graphical abstract: ‘Reverse biomimetic’ synthesis of l-arogenate and its stabilized analogues from l-tyrosine

Supplementary files

Article information

Article type
Edge Article
29 Jun 2021
12 Jul 2021
First published
30 Jul 2021
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., 2021,12, 11394-11398

‘Reverse biomimetic’ synthesis of L-arogenate and its stabilized analogues from L-tyrosine

L. Eagling, D. J. Leonard, M. Schwarz, I. Urruzuno, G. Boden, J. S. Wailes, J. W. Ward and J. Clayden, Chem. Sci., 2021, 12, 11394 DOI: 10.1039/D1SC03554A

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

Read more about how to correctly acknowledge RSC content.

Social activity