Exploiting an Interrelationship between Axial and Planar Chirality in Natural Products Total Synthesis
Lead Research Organisation:
University of Southampton
Department Name: Sch of Chemistry
Abstract
In recent years Nature has revealed some intriguing molecular targets with extraordinary stereochemical features. Most prominent are the vancomycins and related cyclic peptides, where different stereoelements (atom centred, axial, planar and cyclo stereoisomerism) co-exist within a single molecule. To confuse matters further, the various stereoelements may or may not be interrelated, making it hard to apply standard nomenclature when describing such entities. We believe that in many cases planar chirality rather than axial chirality is the important determinant differentiating two diastereoisomers of a given natural product. Our plan is to demonstrate this by using a radical induced transannular ring contraction under kinetic control to prepare a planar chiral phenanthrene within a macrocyclic structure. This will exist as two distinct diastereoisomers at room temperature, each with different faces of the phenanthrene enumbered by the encircling macrocycle. A high energy barrier for isomerisation will ensure that planar chirality is preserved on conversion of the phenanthrene to a biaryl. The latter will automatically be create with the correct axial-chirality, as these two stereoelements are interrelated. To the best of our knowledge this tactic has never previously been exploited in the context of total synthesis.
Organisations
People |
ORCID iD |
David Harrowven (Principal Investigator) |
Description | We are developing methods and strategies for making molecules that have never been prepared before in spite of worldwide interest in their potential use as medicines. |
Exploitation Route | I have recruited a student funded by the EU and progress has been far greater and at substantially lower cost. |
Sectors | Chemicals |
Description | The project is on-going thanks to a follow-on grant from the EU. It is hoped that we will soon complete the total synthesis and publish in a leading journal. Results attained thus far have been communicated at several meetings and conferences. |
First Year Of Impact | 2014 |
Sector | Chemicals |
Impact Types | Cultural |
Description | InterReg IV (AIChem) |
Amount | € 4,500,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 07/2011 |
End | 06/2015 |
Description | InterReg IV (ISCE) |
Amount | € 6,500,000 (EUR) |
Organisation | European Commission |
Sector | Public |
Country | European Union (EU) |
Start | 06/2009 |
End | 03/2014 |