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Yusuf Hamied Department of Chemistry

 

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. Professor Paterson retired in October 2021 and is no longer accepting graduate students and postdocs.

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

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
– Org Biomol Chem
(2018)
16,
8286
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
– Chem Commun (Camb)
(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
– Organic & biomolecular chemistry
(2018)
16,
1343
Challenges and discoveries in the total synthesis of complex polyketide natural products
I Paterson, NYS Lam
– J Antibiot (Tokyo)
(2017)
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
– Investigational 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
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Research Groups

Research Interest Group

Telephone number

01223 336407

Email address

ip100@cam.ac.uk