This review intends to provide the reader with a clear and concise overview of how preparative continuous flow organic chemistry could potentially impact on current important societal challenges. These societal challenges include health/well‐being and sustainable development. Continuous flow chemistry has enabled significant advances for the manufacturing of pharmaceuticals, as well as for biomass valorization toward a biosourced chemical industry. Examples related to pharmaceutical production are herein focused on (a) the implementation of flow chemistry to reduce the occurrence of drug shortages, (b) continuous flow manufacturing of orphan drugs, (c) continuous flow preparation of active pharmaceuticals listed on the WHO list of essential medicines and (d) perspectives for the manufacturing of peptide‐based pharmaceuticals. Examples related to sustainable development are focused on the valorization of biosourced platform molecules. Besides positive impacts on societal challenges, this review also illustrates some of the potentially most threatening perspectives of continuous flow technology within the actual context of terrorism and drug abuse.

Cyclic peptide-based therapeutics have a promising growth forecast that justifies the development of microfluidic systems dedicated to their production, in phase with the actual transitioning toward continuous flow and microfluidic technologies for pharmaceutical production. The application of the most popular method for peptide cyclization in water, i.e., native chemical ligation, under microfluidic conditions is still unexplored. Herein, we report a general strategy for fast and efficient peptide cyclization using native chemical ligation under homogeneous microfluidic conditions. The strategy relies on a multistep sequence that concatenates the formation of highly reactive S-(2-((2-sulfanylethyl)amino)ethyl) peptidyl thioesters from stable peptide amide precursors with an intramolecular ligation step. With very fast ligation rates (<5 min), even for the most difficult junctions (including threonine, valine, isoleucine, or proline), this technology opens the door toward the scale-independent, expedient preparation of bioactive macrocyclic peptides.

Continuous flow preparation of antidepressant ketamine and analogs under sustainable conditions.

The unique reactivity profile of -chloronitroso derivatives is expressed to its fullest potential through the development of an integrated, modular and scalable continuous flow process for the electrophilic α-aminohydroxylation of...

A unique multifaceted approach involving the interplay of NMR, XRD, LC, DFT and MS/IM-MS techniques toward the understanding of the peculiar isomer-selective reduction of (α)-hydroxyiminophosphonates into (α)-hydroxyaminophosphonate derivatives.

Herein is described the development of an intensified continuous flow process for the preparation of a library of alkyl phosphonates through a Michaelis–Arbuzov rearrangement. A careful process optimization and thorough analysis of the competitive reactions led to a very attractive protocol with unprecedented productivities (up to 4.97 kg of material per day) and a low environmental footprint with the absence of solvent, additives, catalysts, and waste. In-line low-field 31P NMR monitoring was conveniently implemented for rapid optimization and process monitoring. Two key alkyl phosphonate intermediates were also assessed for the unprecedented diazene dicarboxylate-mediated electrophilic amination under continuous flow conditions toward the α-aminophosphonic acid derivatives of Pphenylalanine and Palanine, bioisosters of the natural amino acids phenylalanine and alanine, respectively.

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