Abstract
A milder and more efficient procedure for the synthesis of sulfonamides by activating sulfonic acid groups as the corresponding sulfonate esters of ethyl 2-cyano-2-(hydroxyimino)acetate (Oxyma) is reported. This method is greener than all other existing protocols for the purpose. Other important advantages lie in (a) its applicability to less nucleophilic anilines under ambient and milder conditions and (b) its compatibility with solid phase peptide synthesis and acid-labile groups such as trityl (Trt) and tBu, which empowers the solid phase synthesis of sulfonamides of various peptides. To illustrate this, the syntheses of three sulfonamide derivatives of the peptide GAILG-NH2, which is relevant in the context of drug design against type 2 diabetes, are demonstrated by using Fmoc-based solid-phase peptide synthesis (SPPS). The activation of sulfonic acids as their corresponding O-sulfonate esters facilitates sulfonamide synthesis, which can be applied to those substrates that possess acid-labile functional groups and is compatible with solid phase synthesis.
Original language | English |
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Pages (from-to) | 2627-2633 |
Number of pages | 7 |
Journal | European Journal of Organic Chemistry |
Issue number | 13 |
DOIs | |
State | Published - 1 May 2013 |
Externally published | Yes |
Keywords
- Esters
- Medicinal chemistry
- Peptides
- Solid-phase synthesis
- Sulfonamides
- Synthesis design
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry