‘Spiro-ing’ out of control

Posted on 27 June 2016

York team wins EPSRC grant to make medicinally important ‘spirocyclic’ molecules

Professor Peter O'Brien, Professor Richard Taylor and Dr Will Unsworth

Dr. Will Unsworth and Professors Richard Taylor and Peter O’Brien recently heard that a new EPSRC research grant proposal had been chosen for funding.  It is entitled “Spirocycles, Carbocycles and Heterocycles: Unified Routes via Catalyst Selection” and the project funds a postdoctoral research fellow for 3 years (EP/N035119/1; £508, 000).  The research is fundamentally concerned with the development of new methods to make medicinally important molecules: a summary of the research, based on the grant application, is below.

Rapid access to structurally diverse organic compounds is the cornerstone of lead generation in the pharmaceutical and agrochemical industries, essential to meet the burgeoning worldwide healthcare and sustenance requirements. There is a growing realisation that traditional lead identification programmes have been limited in terms of their treatment of 3D structures and there is much current research based on the investigation of molecules which cover wider regions of chemical space.  However, synthetic approaches to generate 3D molecular architectures are typically time-consuming and labour-intensive, and separate routes are traditionally required to access different types of structure (Figure 1a).Figure showing schematic of reactions

The concept underpinning this proposal is that synthetic routes will be designed to generate high energy reactive intermediates with broad synthetic potential, which by judicious choice of catalyst can be converted into several diverse scaffolds via different rearrangement processes (Figure 1b).  It is planned to generate the key reactive precursors from cheap, readily available starting materials, initially building on research from the groups of Taylor and Unsworth in dearomatisation/C-H insertion/rearrangements, to form the requisite high energy intermediates.  3D Shape analysis and evaluation of drug/agrochemical ‘lead-like’ properties will be carried out in the O’Brien group.