Professor Peter O'Brien
Development of New Methods in Synthesis and Medicinal Chemistry
The O’Brien group’s research focuses on the development of new methods for organic synthesis. Projects in the group aim to develop novel, selective and synthetically useful methods that are technically simple, high yielding and robust. A key area is asymmetric and mechanistic organolithium chemistry and we apply the newly developed methodology to the synthesis of common motifs in blockbuster pharmaceuticals. We also synthesise novel 3-D fragments for use in fragment-based drug chemistry.
Current research projects are focused in two areas:
We also have on-going projects in the areas of spirocycle synthesis, fragment-based discovery of enzyme activators and the development of new synthetic methods using electrochemically generated radicals.
Selected recent publications
- Gram-Scale Synthesis of the (−)-Sparteine Surrogate and (−)-Sparteine
Angew Chem Int Ed, 2018, 57, 223.
- Increase of enzyme activity through specific covalent modification with fragments
Chem Sci, 2017, 8, 7772.
- General Procedures for the Lithiation/Trapping of N-Boc Piperazines
J Org Chem, 2017, 82, 7023.
- Synthesis of Enantiopure Piperazines via Asymmetric Lithiation-Trapping of N-Boc Piperazines: Unexpected Role of the Electrophile and Distal N-Substituent
J Am Chem Soc, 2016, 138, 651.
- Mechanistic Interrogation of the Asymmetric Lithiation-trapping of N-Thiopivaloyl Azetidine and Pyrrolidine
Chem Commun, 2016, 52, 1354.
- Silver(I) or copper(II)-mediated dearomatisation of aromatic ynones: direct access to spirocyclic scaffolds
Angew Chem Int Ed, 2015, 54, 7640.
- Lead-oriented synthesis: investigation of organolithium-mediated routes to 3-D scaffolds and 3-D shape analysis of a virtual lead-like library
Bioorg Med Chem, 2015, 23, 2680.
- Revisiting the sparteine surrogate: development of a resolution route to the (–)-sparteine surrogate
Org Biomol Chem, 2014, 12, 9357.
- Asymmetric Lithiation-Trapping of N-Boc Heterocycles at Temperatures above –78 °C
Org Lett, 2013, 15, 5424.
- Preparation and Reactions of Enantiomerically Pure a-Functionalised Grignard Reagents
J Am Chem Soc, 2013, 135, 8071.
- Stereocontrolled Synthesis of the AB Rings of Samaderine C
Org Lett, 2013, 15, 394.
- An Experimental and In Situ IR Spectroscopic Study of the Lithiation–Substitution of N-Boc 2-phenylpyrrolidine and piperidine: Controlling the Formation of Quaternary Stereocenters
J Am Chem Soc, 2012, 134, 5300.
- Enantioselective, Palladium-Catalyzed a-Arylation of N-Boc Pyrrolidine: In Situ React IR Spectroscopic Monitoring, Scope and Synthetic Applications
J Org Chem, 2011, 76, 5936.