skip to content

Department of Chemistry

 
Portrait of ip100

Research in the group ranges across the total synthesis of biologically active natural products and structural analogues to the discovery and development of new synthetic methods.


Stereocontrolled Synthesis of Bioactive Natural Products and Structural Analogues


Representative targets include rare anticancer polyketides of both marine and terrestrial origin such as 1-4 below. For example, dictyostatin (1) shares the same microtubule-stabilising mechanism as the clinically important anticancer drug Taxol, while spirastrellolide A (2) is a potent inhibitor of protein phosphatase 2A. Likewise, chivosazole A (3) and reidispongiolide A (4) are novel actin-interacting macrolides isolated from myxobacteria and marine sponges respectively, which also represent challenging synthetic targets. In all these cases, the initial uncertainty over the stereochemistry, combined with their natural scarcity, has adversely affected their development. Efficient and flexible synthetic routes for the modular construction of these and other complex polyketide natural products are being pursued to establish their full configurations and provide a sustainable supply for detailed biological evaluation. A parallel objective is to design simplified analogues and hybrids that retain the exceptional cancer cell growth inhibitory properties whilst increasing their synthetic accessibility.



New Synthetic Methods


There is a need for new and more efficient methods of synthesis, particularly ones that achieve high levels of stereochemical control, where the development of asymmetric aldol methodology is of particular interest. These new methods are being applied to the synthesis of a wide variety of biologically important natural products.


 


Selected Publications


  • Dictyostatin and hybrids with discodermolide and taxol. Chem. Asian J. (2011), 6, 459; Tetrahedron (2010), 66, 6534
  • Spirastrellolide A. Angew. Chem. Int. Ed. (2012), 51, 2749; Org. Biomol. Chem.  (2012), 10, 5861 and 5873
  • Polyketide natural products as anticancer drug candidates. Org. Lett.  (2013), 15, 3118; Angew. Chem. Int. Ed. (2013), 52, 6517; Angew. Chem. Int. Ed. (2011), 50, 3219Curr. Opin. Drug Discov. Devel. (2010), 13, 777
  • Natural product synthesis using asymmetric aldol reactions. Angew. Chem. Int. Ed. (2013), 52, 9097

Publications

Toward the total synthesis of patellazole B: synthesis of an advanced C1-C25 fragment corresponding to the macrocyclic skeleton
I Paterson, A Phillips, M Anketell, T Balan, N Lam, S Williams
– Organic and Biomolecular Chemistry
A fluorescence anisotropy assay to discover and characterize ligands targeting the maytansine site of tubulin
G Menchon, AE Prota, D Lucena-Agell, P Bucher, R Jansen, H Irschik, R Müller, I Paterson, JF Díaz, K-H Altmann, MO Steinmetz
– Nature Communications
(2018)
9,
2106
A synthesis-enabled relative stereochemical assignment of the C1-C28 region of hemicalide
BY Han, NYS Lam, CI MacGregor, JM Goodman, I Paterson
– Chemical communications (Cambridge, England)
(2018)
54,
3247
Toward aplyronine payloads for antibody-drug conjugates: total synthesis of aplyronines A and D.
N AnŽiček, S Williams, MP Housden, I Paterson
– Org Biomol Chem
(2018)
16,
1343
Challenges and discoveries in the total synthesis of complex polyketide natural products.
I Paterson, NYS Lam
– The Journal of antibiotics
(2018)
71,
215
Induction of accelerated senescence by the microtubule-stabilizing agent peloruside A.
A Chan, C Gilfillan, N Templeton, I Paterson, PT Northcote, JH Miller
– Invest New Drugs
(2017)
35,
706
Structural Basis of Microtubule Stabilization by Discodermolide.
AE Prota, K Bargsten, M Redondo-Horcajo, AB Smith, C-PH Yang, HM McDaid, I Paterson, SB Horwitz, J Fernando Díaz, MO Steinmetz
– Chembiochem
(2017)
18,
905
Zampanolide, a Microtubule-Stabilizing Agent, Is Active in Resistant Cancer Cells and Inhibits Cell Migration.
JJ Field, PT Northcote, I Paterson, K-H Altmann, JF Díaz, JH Miller
– International journal of molecular sciences
(2017)
18,
971
Studies toward a scalable second-generation total synthesis of the aplyronines as novel payloads for antibody-drug conjugates
N Anzicek, S Williams, M Housden, I Paterson
– ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2017)
253,
Towards the total synthesis and structural determination of patellazole B
A Phillips, T Balan, M Anketell, S Williams, I Paterson
– ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2017)
253,
  • 1 of 31
  • >

Research Group

Research Interest Group

Telephone number

01223 762018 (fax)
36407

Email address

ip100@cam.ac.uk