Details of Grant 

EPSRC Reference:	EP/F025734/1
Title:	Synthesis of the Brasilinolides
Principal Investigator:	Paterson, Professor I
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Cambridge
Scheme:	Standard Research
Starts:	01 November 2007	Ends:	30 April 2011	Value (£):	435,374
EPSRC Research Topic Classifications:	Biological & Medicinal Chem. Medical science & disease
EPSRC Industrial Sector Classifications:	Pharmaceuticals and Biotechnology
Related Grants:
Panel History:	Panel Date Panel Name Outcome 10 Oct 2007 Chemistry Prioritisation Panel (Science) Announced
Summary on Grant Application Form
The polyketides represent a diverse array of structurally complex natural products having a wide range of biological activity, typically antibiotic, antitumour, antifungal or immunosuppressive action, with many members having important therapeutic utility in human medicine. This project falls within the general theme of complex polyketide synthesis and focuses on the total synthesis of the brasilinolides, which are a novel family of potent immunosuppressive and antifungal 32-membered macrolides with unprecedented structural and stereochemical complexity. The planned synthesis of the brasilinolides draws on and extends contemporary methods of acyclic stereocontrol to efficiently set up the required stereochemistry, with particular emphasis on the use of new methodology recently developed in the Cambridge group. Our approach aims to incorporate maximum flexibility in terms of segment coupling, enabling the synthesis of other stereoisomers if necessary as well as novel analogues, and relies on a versatile combination of reagent and substrate-based control. Altogether, the pronounced biological activities of the brasilinolides, along with their lack of acute toxicity, makes further evaluation as new immunotherapeutic and/or antifungal agents of interest, with potential applications inter alia to autoimmune diseases and in counteracting tissue rejection in organ transplantation. These considerations, along with the significant intellectual challenge and high quality training provided by tackling such complex molecule synthesis, make the brasilinolides an attractive and platform for developing new methodology and strategies, which is also expected to become an exciting arena for further chemical and biological studies. Significantly, this project will build on the considerable expertise that we have developed over the years on the stereocontrolled synthesis of bioactive natural products and their analogues.
Key Findings
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Potential use in non-academic contexts
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Impacts
Description This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk Summary Date Materialised
Sectors submitted by the Researcher
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
Project URL:
Further Information:
Organisation Website:	http://www.cam.ac.uk