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 |
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Format: | Artikel |
Sprache: | eng |
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Zusammenfassung: | 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. |
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ISSN: | 1523-7060 1523-7052 |
DOI: | 10.1021/acs.orglett.2c00266 |