Literature search about the impact of green chemistry on solid-phase peptide synthesis

Abstract

Solid-phase peptide synthesis is a widely used strategy today, to produce peptides that can later be used in the pharmaceutical industry as they have therapeutic properties, among many others. In order to produce a peptide, throughout the synthesis solvents, reagents, additives, and bases are used that are considered toxic, dangerous, and even some have restrictions on their use. In addition, the strategy generates a large amount of waste because it is usual to work with an excess of reagents and a number of washes have to be performed. As it is a widely used synthesis, both at an industrial and research level, and thanks to the awareness of the ecological footprint that has been growing in recent years, the synthesis of peptides is being influenced by the use of green chemistry. That is, ecological alternatives to traditional products have been studied over the last few years, with the aim of producing peptides with similar yields and purities to those obtained with the classical approach but reducing toxicity and waste. In this work, a bibliographic study has been carried out on the green alternatives that have been investigated over the last years from the information given by recent reviews (2019 and 2020). Since the synthesis published by Merrifield for the first time dated in 1963, it was not until the decade of the present century that green chemistry has begun to be involved in the seek of synthetic alternatives more healthy and amenable to the environment. Several protocols have been proposed so far that replace the traditional products with less harmful and more compatible with the green chemistry postulates, and that have been considered promising by researchers according to the results achieved in different aspects of the synthesis (resin swelling, the solubility of reagents, yields and purities). This work tries to give the state-of-the-art in this field