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.

Keywords: bioactive molecules; continuous flow chemistry; enabling technologies; medicinal chemistry; photocatalysis; photochemistry; process development.

Figure 1

Images of a falling film reactor plate (reproduced with permission from [25]) and the Corning G3 photoreactor [26].

Figure 2

Image of the nebulizer-based photo-reactor (reproduced with permission from [27]).

Figure 3

Image of the photochemical reactor set up (reproduced with permission from [28]).

Figure 4

Representations of the vortex fluidic device. (A) A schematic of the vortex fluidic device; (B) A photograph of the vortex fluidic device; (reproduced with permission from [30]).

Figure 5

Representations of the firefly photoreactor. (a) Diagram of reactor; (b) Firefly reactor in operation; (reproduced with permission from [31]) .

Figure 6

Images of the Vapourtec high-power LED reactor and Uniqsis’s PhotoSyn reactor.

Figure 7

Exploiting solar light for scaled luminescent solar concentrators (LSC) applications (reproduced with permission from [48]).

Figure 8

Structures of complex bioactive molecules featuring flow photochemistry key steps.

Figure 9

Structures of poly(ADP-ribose) polymerase inhibitors and natural product analogues prepared in flow.

Figure 10

Continuous photosynthesis of pyocyanin (reproduced with permission from [61]).

Figure 11

Structures of drug-like heterocyclic entities prepared photochemically and their precursors. (A) synthesis of 2,4-Methanopyrrolidines; (B) synthesis of 3-hydroxyazetidines; (C) photobenzylation of substituted phthalimides.