Continuous Flow Photochemistry for the Preparation of Bioactive Molecules

Abstract

The last decade has witnessed a remarkable development towards improved and new photochemical transformations in response to greener and more sustainable chemical synthesis needs. Additionally, the availability of modern continuous flow reactors has enabled widespread applications in view of more streamlined and custom designed flow processes. In this focused review article, we wish to evaluate the standing of the field of continuous flow photochemistry with a specific emphasis on the generation of bioactive entities, including natural products, drugs and their precursors. To this end we highlight key developments in this field that have contributed to the progress achieved to date. Dedicated sections present the variety of suitable reactor designs and set-ups available; a short discussion on the relevance of greener and more sustainable approaches; and selected key applications in the area of bioactive structures. A final section outlines remaining challenges and areas that will benefit from further developments in this fast-moving area. It is hoped that this report provides a valuable update on this important field of synthetic chemistry which may fuel developments in the future.

UV‐Induced 1,3,4‐Oxadiazole Formation from 5‐Substituted Tetrazoles and Carboxylic Acids in Flow

“…This observation was important when considering the next stage of optimization, as we envisaged translation of the reaction into a flow process. This was anticipated to maximize the light‐uptake of the reaction mixture through an increase in interfacial surface area which had been shown to reduce the reaction time in previous work [24–28] . Clearly, a build‐up of precipitate would hinder the integrity of the flow system and irradiation.…”

“…This was anticipated to maximize the light-uptake of the reaction mixture through an increase in interfacial surfacea rea which had been shown to reduce the reactiont ime in previous work. [24][25][26][27][28] Clearly,abuild-up of precipitate would hindert he integrity of the flow system and irradiation. To reduce this risk, the concentration was reduced from 0.12 m to 0.04 m;however, the initial attemptw as unsuccessful with ap recipitate obstructing the flow system.…”

Continuous Flow Organophosphorus Chemistry

“…Seven different enzymes were immobilized on nickel agarose beads and packed inside a reactor to perform the biocatalyzed synthesis towards sugar nucleotide 28 (Figure 8). Galactose (26) is firstly phosphorylated into galactose 1phosphate (27) using adenosine triphosphate (ATP). 27 is next converted into 28 using uridine diphosphate glucose (UDP-Glc) as a nucleotide source.…”

“…[23][24][25] With its potential to overcome some of the common issues encountered with batch protocols, flow chemistry has thrived in the many research areas inherent of or at the interface with Organic Chemistry, including methodology, medicinal chemistry, total synthesis, physical organic chemistry and process chemistry to name a few. [26][27][28][29][30][31][32][33][34][35][36] Organophosphorus reagents are widespread for a wide range of reference reactions and organophosphorus chemistry has so many ties towards industrial applications with immense markets and volumes, including pharmaceuticals and agrochemicals. It is therefore not surprising to witness a revisit of organophosphorus chemistry by flow chemists with unquestionable advantages.…”

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

“…The renaissance of photochemistry that occurred over the last decade has been described as "old light through new windows", and much of this work centered on the combination of light with continuous flow reactors [1][2][3][4][5][6]. The reason for this increased interest is that continuous flow photochemical reactors can overcome various limitations that occur when the same reaction run in batch reactors [7]. For example, the flow reactor can overcome the difficulties that occur upon scale-up.…”