Open Access
CC BY 4.0 · Synlett
DOI: 10.1055/a-2564-4920
letter

A Diastereoselective Mizoroki–Heck Reaction for Synthesis of Spirooxindole-Based Nonnatural Amino Acids Using a Boc-Protected Amine Chiral Auxiliary

Jens Lindman
a   Department of Medicinal Chemistry, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
,
Sharathna Puthiyaparambath
a   Department of Medicinal Chemistry, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
,
b   The Beijer Laboratory, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, BMC, P.O. Box 574, 751 23 Uppsala, Sweden
c   Nanotechnology and Functional Materials, Department of Materials Science and Engineering, Ångström Laboratory, Uppsala University, Lägerhyddsvägen 1, 751 03 Uppsala, Sweden
,
a   Department of Medicinal Chemistry, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
,
b   The Beijer Laboratory, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, BMC, P.O. Box 574, 751 23 Uppsala, Sweden
› Author Affiliations

We thank Uppsala University and the Kjell and Märta Beijer Foundation for their support.


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Abstract

Nonnatural amino acids are pivotal for expanding the functional diversity of peptides and proteins, enabling novel therapeutic opportunities. Mono-Boc-protected spirocyclization precursors have been developed as versatile intermediates for the diastereoselective synthesis of spirooxindole-based nonnatural amino acids by the Mizoroki–Heck reaction. Catalytic hydrogenation produced cyclopentyl derivatives, expanding the diversity of these amino acids. Furthermore, one spirooxindole derivative was incorporated into a tripeptide by solid-phase peptide synthesis on Rink amide resin to demonstrate its potential in peptide modification and drug development.

Supporting Information



Publication History

Received: 21 February 2025

Accepted after revision: 19 March 2025

Accepted Manuscript online:
21 March 2025

Article published online:
29 April 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by/4.0/)

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