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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

Total synthesis and biological evaluation of simplified aplyronine analogues as synthetically tractable anticancer agents.
TR Pettigrew, RJ Porter, SJ Walsh, MP Housden, NYS Lam, JS Carroll, JS Parker, DR Spring, I Paterson
– Chem Commun (Camb)
(2020)
56,
1529
A Unified Total Synthesis of the Actinoallolides, a Family of Potent Anti‐Trypanosomal Macrolides
MJ Anketell, TM Sharrock, I Paterson
– Angewandte Chemie
(2020)
132,
1588
Towards the Total Synthesis of Hemicalide: Synthesis of the C27-C46 Region
TP Stockdale, BY Han, NYS Lam, JM Goodman, I Paterson
– MARINE DRUGS
(2020)
18,
A Unified Total Synthesis of the Actinoallolides, a Family of Potent Anti-Trypanosomal Macrolides
MJ Anketell, TM Sharrock, I Paterson
– Angew Chem Int Ed Engl
(2020)
59,
1572
Stereocontrolled synthesis as an enabling tool for the configurational assignment of marine polyketide natural products
NYS Lam, I Paterson
– European Journal of Organic Chemistry
(2019)
A counterintuitive stereochemical outcome from a chelation-controlled vinymetal aldehyde addition leads to the configurational reassignment of phormidolide A
NYS Lam, G Muir, VR Challa, R Britton, I Paterson
– Chem Commun (Camb)
(2019)
55,
9717
Synthesis-enabled stereochemical assignment of the C1-C28 region of hemicalide: A potent cytotoxic polyketide of marine sponge origin
N Lam, BY Han, C MacGregor, J Goodman, I Paterson
– ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2019)
257,
Designed analogues of the aplyronines for next-generation antibody-drug conjugates
R Porter, T Pettigrew, I Paterson, D Spring, J Parker
– ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2019)
257,
Toward the total synthesis of patellazole B: synthesis of an advanced C1-C25 fragment corresponding to the macrocyclic skeleton
AW Phillips, MJ Anketell, T Balan, NYS Lam, S Williams, I Paterson
– Organic and Biomolecular Chemistry
(2018)
16,
6908
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
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Research Group

Research Interest Group

Telephone number

01223 336407
01223 762018 (fax)

Email address

ip100@cam.ac.uk