Fernando Albericio is Research Professor at the University of KwaZulu-Natal, South Africa, Full Professor at the University of Barcelona, Spain, and Visiting Professor at the King Saud University, Saud Arabia. His major research interests cover practically all methodological aspects of peptide synthesis, as well as synthesis of peptides and small molecules with therapeutic activities, mainly in the field of cancer and infectious diseases. His group is also involved in the development of new strategies for drug delivery.

Professor Albericio has published over 900 scientific paper and co-authored four books. He has filled more than 55 patents. He is Editor in Chief of several scientific journals and acting in the Editorial Board of several others. He has been honored with a Doctorate Honoris Causa by the Universidad de Buenos Aires, Argentina, the Leonidas Zervas award by the European Peptide Society, the Vincent du Vigneaud award by the American Peptide Society, among others. Recently, part of his efforts has been focused to make the peptide synthesis greener and better.

The last few years have witnessed an explosion in the number of peptides approved by regulatory agencies. Peptide chemists are currently facing different challenges. Among them, the synthesis of increasingly complex peptides and the need to make the process greener. In this presentation, we will review our laboratory's efforts in these two directions.

The recently developed SIT for the protection of a Cys allows a chemoselective disulfide formation through a thiol-disulfide interchange approach with a free Cys present in the molecule. Synthesis of several disulfide containing peptides will be discussed.

Based on the safety-catch concept, a fourth category of protecting groups, that are stable under the conditions used to remove the first three and that are removed at the end of the synthetic process, has been developed. This step can be performed when the peptide is still anchored to the resin or once the peptide is in solution. This new concept of protecting group facilitate the synthesis and manipulation of difficult peptides.

From a green perspective, SPPS is hampered by high solvent consumption for the washings after each of the two main steps, namely deprotection and coupling. Here we propose to combine the two steps in one. In this regard, once the coupling was completed, piperidine is added up to a concentration of 20% to the coupling cocktail, and after the removal is finished, a few washings with the corresponding solvent in the presence of an acid rectifier –to remove traces of base– completes the synthetic cycle.

Finally, we will illustrate that the Refractive Index is a process analytical tool suitable for the real-time monitoring of different steps of the SPPS including washings.