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Professor Ian Paterson FRSE FRS

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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


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
Challenges and discoveries in the total synthesis of complex polyketide natural products.
I Paterson, NYS Lam
– The Journal of antibiotics
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
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
An Expedient Total Synthesis of Chivosazole F: an Actin-Binding Antimitotic Macrolide from the Myxobacterium Sorangium Cellulosum
S Williams, J Jin, SBJ Kan, M Li, LJ Gibson, I Paterson
– Angew Chem Int Ed Engl
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
Structural Determinants of the Dictyostatin Chemotype for Tubulin Binding Affinity and Antitumor Activity Against Taxane- and Epothilone-Resistant Cancer Cells
C Trigili, I Barasoain, PA Sánchez-Murcia, K Bargsten, M Redondo-Horcajo, A Nogales, NM Gardner, A Meyer, GJ Naylor, E Gómez-Rubio, F Gago, MO Steinmetz, I Paterson, AE Prota, JF Díaz
– ACS Omega
Strategy Evolution in the Total Synthesis of (−)-Leiodermatolide
I Paterson, S Williams
– Israel Journal of Chemistry
Evaluation of the brain-penetrant microtubule-stabilizing agent, dictyostatin, in the PS19 tau transgenic mouse model of tauopathy.
V Makani, B Zhang, H Han, Y Yao, P Lassalas, K Lou, I Paterson, VMY Lee, JQ Trojanowski, C Ballatore, AB Smith, KR Brunden
– Acta Neuropathologica Communications
Toward the stereochemical assignment and synthesis of hemicalide: DP4f GIAO-NMR analysis and synthesis of a reassigned C16-C28 subunit.
CI MacGregor, BY Han, JM Goodman, I Paterson
– Chemical communications (Cambridge, England)
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Research Group

Research Interest Group

Telephone number

01223 336407
01223 762018 (fax)

Email address