Holistic Approach to Synthesis

Focus Area Definition

The holistic approach to molecular synthesis seeks to change the way synthesis chemists assemble molecules. The intention is to develop a new paradigm for the construction of organic structures in which the feedstock (starting-point) and end product are regarded as parts of a well-defined whole, rather than separate entities as present. Complex molecular syntheses typically have a small number of critical staging posts, signposted by reactions that build complexity. These are linked by sequences of reactions that achieve little other than to prime the molecule to trigger the complexity-generating step. The goal of the holistic approach to synthesis is to reduce the number of priming steps to a minimum so that targets can be made using a small number of complexity-generating reactions. In this way the time taken to accomplish a target-synthesis will be greatly reduced and our ability to access useful new chemical space greatly enhanced.

Challenges and Goals

The major challenges were defined as (click to read more about each individual challenge)

The challenges, the current state-of-the-art, goals and pathways to achieving these goals are summarised in the roadmap below.

Significance to End Users

This will be hugely significant to everyone who does organic synthesis, but real change will take a long time to establish. Industry needs to be involved, because likely there will be significant technological implications. Industry needs to be convinced that this will pay massive dividends for future generations (and almost certainly not the present one(s)). Not all target molecules will be highly complex: there may be shorter-term benefits also.

Current state of the art – Key people in UK – UK Capability issues

Synthesis is the UK (and elsewhere) is in a mature phase, where much activity is from the confines of existing comfort zones. Existing funding models (i.e. responsive-mode) are ill-suited to the proposed radical departure in the way of thinking about synthesis, because peer-review does not favour more speculative, single-PI proposals (where the chemistry might not work as planned). Therefore, the problem requires several institutions with strength in organic synthesis to collaborate closely; it’s not clear whether there is a current mechanism in which this could be made to work effectively.

Which disciplines might be needed – Opportunity for new research communities

  • Synthetic chemistry, Catalysis, Pharma/Agro; and Materials, novel electronic; light-emitting polymers
  • Theoretical/Computational (Lab of the future): see below
  • Analytical Chemistry (and access to it): reactions being developed will need to be monitored in real time in order to establish reaction pathways
  • Chemical Engineering: new chemistries will require new technologies: mixing; rapid heat transfer; removal of by-products which interfere
  • Complexity Science (Multivariate modelling): for DoE approach