A new photochemical method for the preparation of amino acid-alpha-phenylthioesters and peptide-alpha-phenylthioesters

Tyrone Justin Hogenauer, University of Texas at El Paso

Abstract

We describe the development of a novel resin with a photoreactive N-acylnitroindoline linker, that allows for the synthesis of amino acid- (in solution) or peptide-α-thioesters using standard Fmoc/t-Bu standard solid phase peptide synthesis (SPPS). Recent advances have shown that the yields of this thioesterification reaction have dramatically increased due to a simple change in the order of addition of reagents. Upon illumination with UV-light, in the presence of N-hydroxybenzotriazole (HOBt), the amino acid-α- or peptide-α-OBt ester is generated by direct photo-release from the nitroindoline linker with minimal epimerization, followed by reaction with thiophenol in the dark to produce amino acid-α-phenylthioesters or peptide-α-phenylthioesters. ^ Nine amino acid-α-phenylthioesters of the twenty proteinogenic amino acids were prepared in high yield and high purity (75-83). Eight photoreactive tripeptides were prepared on Rink Amide resin following Fmoc-based SPPS strategies and cleaved to give their corresponding photoreactive tripeptide amides (67-74). Seven tripepide-α-phenylthioesters were prepared in high yield and high purity (84-90). Three tripeptide-α-phenylthioesters were prepared in good yield by direct photo-release from the solid support (86, 87, 90). ^ Five photoreactive glycopeptides based on sequences found in human erythropoietin (98 and 99) and the GP-120 HIV-1 envelope protein (100, 101, and 102) were synthesized and cleaved from Rink Amide resin for future conversion to their corresponding thioesters.^

Subject Area

Chemistry, Biochemistry|Chemistry, Organic

Recommended Citation

Hogenauer, Tyrone Justin, "A new photochemical method for the preparation of amino acid-alpha-phenylthioesters and peptide-alpha-phenylthioesters" (2010). ETD Collection for University of Texas, El Paso. AAI3426848.
http://digitalcommons.utep.edu/dissertations/AAI3426848

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