Solid-Phase Synthesis of Head to Side-Chain Tyr-Cyclodepsipeptides Through a Cyclative Cleavage From Fmoc-MeDbz/MeNbz-resins

Gerardo A Acosta; Laura Murray; Miriam Royo; Beatriz G de la Torre; Fernando Albericio

doi:10.3389/fchem.2020.00298

Solid-Phase Synthesis of Head to Side-Chain Tyr-Cyclodepsipeptides Through a Cyclative Cleavage From Fmoc-MeDbz/MeNbz-resins

Front Chem. 2020 Apr 22:8:298. doi: 10.3389/fchem.2020.00298. eCollection 2020.

Authors

Gerardo A Acosta^{1

2

3

4}, Laura Murray^{1

2}, Miriam Royo^{3

4}, Beatriz G de la Torre^{5

6}, Fernando Albericio^{1

2

3

4

6}

Affiliations

¹ CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona (UB), Barcelona, Spain.
² Department of Organic Chemistry, University of Barcelona, Barcelona, Spain.
³ Institute of Advanced Chemistry of Catalonia (IQAC-CSIC), Spanish National Research Council (CSIC), Barcelona, Spain.
⁴ Associated Unit, Spanish National Research Council-University of Barcelona (CSIC-UB), Barcelona, Spain.
⁵ KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
⁶ Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Durban, South Africa.

Abstract

Cyclic depsipeptides constitute a fascinating class of natural products. Most of them are characterized by an ester formed between the β-hydroxy function of Ser/Thr -and related amino acids- and the carboxylic group of the C-terminal amino acid. Less frequent are those where the thiol of Cys is involved rendering a thioester (cyclo thiodepsipeptides) and even less common are the cyclo depsipeptides with a phenyl ester coming from the side-chain of Tyr. Herein, the preparation of the later through a cyclative cleavage using the Fmoc-MeDbz/MeNbz-resin is described. This resin has previously reported for the synthesis of cyclo thiodepsipeptides and homodetic peptides. The use of that resin for the preparation of all these peptides is also summarized.

Keywords: cyclothiodepsipeptides; heterodetic cyclic peptides; homodetic cyclic peptides; native chemical ligation; solid-phase peptide synthesis.