Environmentally Sensible Organocatalytic Fmoc/t‑Bu Solid-Phase Peptide Synthesis

Environmentally Sensible Organocatalytic Fmoc/t‑Bu Solid-Phase Peptide Synthesis

Despite numerous reports on catalytic amide bond formation (ABF), these methods have thus far had a minimal impact on the universal fluorenylmethoxycarbonyl (Fmoc)/t-Bu solid-phase peptide synthesis (SPPS) methodology. We now report a proof-of-principle Fmoc/t-Bu SPPS in which both couplings and Fmo...

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Veröffentlicht in:Organic letters 2022-03, Vol.24 (9), p.1827-1832
Hauptverfasser: Pawlas, Jan, Rasmussen, Jon H
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Sprache:eng
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Amino Acids - chemistry
Fluorenes - chemistry
Peptides - chemistry
Solid-Phase Synthesis Techniques - methods
Solvents
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container_title Organic letters
container_volume 24
creator Pawlas, Jan
Rasmussen, Jon H
description Despite numerous reports on catalytic amide bond formation (ABF), these methods have thus far had a minimal impact on the universal fluorenylmethoxycarbonyl (Fmoc)/t-Bu solid-phase peptide synthesis (SPPS) methodology. We now report a proof-of-principle Fmoc/t-Bu SPPS in which both couplings and Fmoc deprotections were catalyzed by readily available reagents in an inexpensive green solvent. Couplings were carried out with >99% stereoselectivity, employing 1.1 equiv of Fmoc amino acids (AAs), using diisopropylcarbodiimide (DIC) as a coupling agent and 1-hydroxy-1,2,3-triazole-5-carboxylic acid ethyl ester (HOCt) (TON ∼ 30) as a catalyst, while Fmoc deprotections were carried out using 1,8-diazabicyclo(5.4.0)­undec-7-ene (DBU) (TON ∼ 7), facilitating synthesis of a model pentapeptide in 95% HPLC purity while also enabling minimization of solvent washing.
doi_str_mv 10.1021/acs.orglett.2c00266
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subjects Amino Acids - chemistry
Fluorenes - chemistry
Peptides - chemistry
Solid-Phase Synthesis Techniques - methods
Solvents
title Environmentally Sensible Organocatalytic Fmoc/t‑Bu Solid-Phase Peptide Synthesis
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