Sulfonamide synthesis via oxyma-O-sulfonates - Compatibility to acid sensitive groups and solid-phase peptide synthesis

Nani Babu Palakurthy, Dharm Dev, Shubhasmin Rana, Krishna Chaitanya Nadimpally, Bhubaneswar Mandal

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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 languageEnglish
Pages (from-to)2627-2633
Number of pages7
JournalEuropean Journal of Organic Chemistry
Issue number13
DOIs
StatePublished - 1 May 2013
Externally publishedYes

Keywords

  • Esters
  • Medicinal chemistry
  • Peptides
  • Solid-phase synthesis
  • Sulfonamides
  • Synthesis design

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Sulfonamide synthesis via oxyma-O-sulfonates - Compatibility to acid sensitive groups and solid-phase peptide synthesis'. Together they form a unique fingerprint.

Cite this