Eco-Friendly Synthesis of Peptides Using Fmoc-Amino Acid Chlorides as Coupling Agent Under Biphasic Condition

Santosh    Y.    Khatavi; Kamanna      Kantharaju

doi:10.2174/0929866527666201119161116

Abstract

Background: Agro-waste derived solvent media act as a greener process for the peptide bond formation using N^α-Fmoc-amino acid chloride and amino acid ester salt with in situ neutralization and coupling under biphasic condition. The Fmoc-amino acid chlorides are prepared by the reported procedure of freshly distilled SOCl₂ with dry CH₂Cl₂. The protocol found many added advantages such as neutralization of amino acid ester salt and not required additional base for the neutralization, and directly coupling take place with Fmoc-amino acid chloride gave final product dipeptide ester in good to excellent yields. The protocol occurs with complete stereo chemical integrity of the configuration of substrates. Here, we revisited Schotten-Baumann condition, instead of using inorganic base.

Objective: To develop green protocol for the synthesis of peptide bond using Fmoc-amino acid chloride with amino acid esters salt.

Methods: The final product isolated is analyzed in several spectroscopic and analytical techniques such as FT-IR, ¹H-, ¹³C-NMR, Mass spectrometry and RP-HPLC to check stereo integrity and purity of the product.

Conclusion: The present method developed greener using natural agro-waste (lemon fruit shell ash) derived solvent medium for the reaction and not required chemical entity.

Keywords: Agro-waste, peptide, green chemistry, racemization free, Fmoc-amino acid chloride, neutralization.

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Graphical Abstract

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