Expand Flow – Accessing new chemical space via a combined flash- and photochemical flow chemistry approach for the functionalisation and ring expansion of heterocycles

Objective

With ever-increasing costs for the development of new drugs, the call for the development of more cost-effective and efficient methodologies to streamline the access to new drug candidates is imperative. To access new chemical space, the ring-distortion strategy – late-stage modification of rings to a variety of different functionalized cyclic and acyclic motifs – has proven a particularly successful approach. Recently, numerous ring-expansion and functionalisation protocols to cyclopentanones, tetralones, γ-functionalized butanones from cyclobutanols have been developed using classical batch processes. Despite the advances, the translation to pharmaceutically relevant applications is still outstanding; mainly due to three factors:
1)The application of heterocycles in these protocols has been very limited or even impossible
2)The two-carbon ring expansion has only been successful on aryl-substituted analogues, yet not on alkene-substituted analogues &
3)Scale-up to practical quantities is often difficult due to the requirement for conditions difficult to realise using batch processing.
Expand Flow presents a multidisciplinary project that lies in the intersection of flash chemistry and synthetic photo-catalysis with microfluidic engineering and computational chemistry for the development of a selective, sustainable and applicable methodology for the ring deconstruction and functionalisation of heterocycles. Ultimately, its applicability to the pharmaceutical industry will be proven by the total synthesis of THC and its hitherto unexplored heterocyclic analogues.
Overall, this project will add a valuable tool to the synthetic chemist’s repertoire for the rapid, environmentally-friendly and cost-effective development of new drug candidates by the versatile functionalisation of various heterocycles. This innovative approach will have a high scientific, technological and societal impact, reinforcing the European competitiveness in the development of life-saving drugs.

Fields of science (EuroSciVoc)

CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.

• natural sciences chemical sciences catalysis photocatalysis

Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

• Flash chemistry
• photochemical flow chemistry
• ring expansion
• tetrahydrocannabinol

Coordinator