Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 11394-11398 |
| Number of pages | 5 |
| Journal | Chemical Science |
| Volume | 12 |
| Issue number | 34 |
| Early online date | 30 Jul 2021 |
| DOIs | |
| Publication status | Published - 1 Sept 2021 |
Bibliographical note
Funding Information:This work was funded by the EPSRC through the Bristol Chemical Synthesis Centre for Doctoral Training (EP/L015366/1), the Bristol Centre for Doctoral Training in Technology-Enhanced Chemical Synthesis (EP/S024107/1), research grant EP/L018527, and an Impact Acceleration Award; by Syngenta through a CASE award (to L. E)., by the ERC through Advanced Grant ROCOCO and Proof of Concept Grant QUATERMAIN, and by the Basque Government through a fellowship (to I. U.). We thank Prof Maxwell Crossley for informative discussions. We acknowledge the preliminary investigations carried out by Greg McHugh and we dedicate this paper to his memory.
Funding Information:
This work was funded by the EPSRC through the Bristol Chemical Synthesis Centre for Doctoral Training (EP/L015366/ 1), the Bristol Centre for Doctoral Training in Technology- Enhanced Chemical Synthesis (EP/S024107/1), research grant EP/L018527, and an Impact Acceleration Award; by Syngenta through a CASE award (to L. E)., by the ERC through Advanced Grant ROCOCO and Proof of Concept Grant QUATERMAIN, and by the Basque Government through a fellowship (to I. U.). We thank Prof Maxwell Crossley for informative discussions. We acknowledge the preliminary investigations carried out by Greg McHugh and we dedicate this paper to his memory.
Publisher Copyright:
© The Royal Society of Chemistry 2021.
Research Groups and Themes
- BCS and TECS CDTs