Dictyosphaeric Acids, Colletofragarones and Novel Drug Discovery Scaffolds: Doubly Tethered Intramolecular-Michael Approach
Lead Research Organisation:
University of York
Department Name: Chemistry
Abstract
Dictyosphaeric acid A, a recently-discovered natural product, has been shown to inhibit methicillin-sensitive Staphylococcus aureus and MRSA. The closely related colletofragarones are also biologically active (germination self-inhibitors). The unique tricyclic core present in both families of natural products appears to represent a privileged template for SAR studies. Efficient new methodology, based particularly around the novel doubly tethered intramolecular Michael approach , but also utilising alkene metathesis and Stille coupling, has been designed to provide rapid access to key tricyclic core of these compounds. This methodology will be optimised and employed to prepare key templates which will be elaborated to give a range of novel, simplified analogues for SAR studies. The same methodology will also used as the cornerstone of total syntheses of dictyosphaeric acid A and dictyosphaeric acid B. Similarly, the methodology will then be applied to prepare the colletofragarones A1 and A2 (and so enable the stereochemistry of these natural products to be confirmed).
Organisations
People |
ORCID iD |
Richard Taylor (Principal Investigator) |
Publications
Alan Burns
(2010)
Serendipty in natural product synthesis
Burns AR
(2010)
Total synthesis and structural reassignment of (+)-dictyosphaeric acid A: a tandem intramolecular Michael addition/alkene migration approach.
in Angewandte Chemie (International ed. in English)
Hookins D
(2010)
A double oxidation procedure for the preparation of halogen-substituted para-benzoquinone monoketals: asymmetric synthesis of (-)-harveynone
in Tetrahedron Letters
Moody C
(2011)
A one-pot oxidation/allylation/oxidation sequence for the preparation of ß,?-unsaturated ketones directly from primary alcohols
in Tetrahedron Letters
Description | New methods for combining conventional chemical reactions to streamline the preparation of target molecules have been developed. |
Exploitation Route | The new methods are widely applicable and citations indicate general acceptance. |
Sectors | Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology |
Description | The new methods have been used by us to prepare target compounds (and to correct the erroneous structure of a potential drug). |
First Year Of Impact | 2010 |
Sector | Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology |
Impact Types | Economic |