Sharma – Synthetic organic chemistry: Heterocycles and natural product synthesis
The development of new methods to synthesise functional molecules remains central to organic synthesis. Our group’s research focus is towards developing new synthetic methodology that delivers structurally diverse and complex chemical entities via rapid fusion of short lived reactive species. Our particular emphasis is towards up-valuing and reintroducing under-represented reagents by exploring their latent reactivity for heterocycles, spirocycles and natural products & analogue synthesis.
Working with our collaborators, we further seek to find novel application of these molecules in the field of biological, medicinal and material sciences.
Heterocycles and spirocycles
‘Single-reagent—diverse-scaffolds’: Cyanamides. Heteroatom-containing cyclic structures are at the heart of the pharmaceutical and medicinal sciences. We are engaged in the development of new chemical technologies aimed towards the synthesis of heterocyclic scaffolds to probe biological system. Most recently our research focus has been on the N-C-N linkage of substituted ‘cyanamides’. We have harnessed the intrinsic electro- and nucleo-philic duality of cyanamides towards construction of novel group of nitrogen rich heterocycles under an unprecedented formal 1,3-dipolar reaction with short lived dipoles. Our method for the first time demonstrates the incorporation of the cyanamide N1-nitrogen directly into the core of the ring with the nitrile (-CN2) forming the exocyclic imines. So far we have demonstrated a sustainable and rapid entry route to a range of biologically important cores such as oxadiazol-5-imines, imidines, oxadiazolones, triazol-3-imines and triazolones.
‘Spiro-click technology’: 3D Scaffolds: Rigid, three-dimensional molecular scaffolds, which provide unique entry to under-explored regions of 3D chemical space, have recently formed an indispensable tool in the search for new lead compounds; spirocyclic compounds occupying a prominent position in this area. However, synthetic approaches to such non-planar organic architectures are often time-consuming and labour-intensive. We seek to develop new methodology based on our cyanamide chemistry for the rapid access to heteroatom-rich complex spiro system.
Natural product and analogue synthesis
Natural products (NP) remains one of the major source for novel structures for drug discovery programme. We have long standing interest in the total synthesis of biologically relevant natural products and we continue to seek new and interesting targets to accomplish total synthesis. Conjugating NP with other privileged structures is emerging as new and powerful tools to diversify and re-introduce NP into the drug discovery technology. This technology help overcome the shortage of supply of new and novel structure with increased complexity, variability, together combined with natural product like features. Combining our click-spiro technology with existing active NP we intend to explore synthesis of new NP based 3D structures.
Meet the team