Work

Orthogonal Cleavage of the HMPB Linker from Solid Support Using HFIP

Year: 2025

Type: article

Abstract: Hexafluoroisopropanol (HFIP) is widely used as a hydrogen-bond-donor solvent. Here we demonstrate that 4-(4-hydroxymethyl-3-methoxyphenoxy)butyric acid (HMPB), a commonly used linker for generating C-terminal carboxylic acid peptides, cleaves from the solid support at HFIP concentrations as low as 20% in dichloromethane. The resulting yields are comparable to concentrated trifluoroacetic acid cleavage conditions. This reactivity is attributed to an added resonance structure, enabled by a p -methoxy substituent, which potentially stabilizes the benzylic carbocation intermediate during cleavage.

Source: Organic Letters

DOI: 10.1021/acs.orglett.5c04086

Authors: Michael Desgagné, Dennis A. Kutateladze, Bradley L. Pentelute

Institutions: Massachusetts Institute of Technology, Broad Institute, Koch Institute for Integrative Cancer Research At MIT

Language: English

Topic: Chemical Synthesis and Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,500