2. New Methods for the Synthesis of Polyketide Natural Products

New and practical methods for the stereocontrolled synthesis of bioactive, polyketide natural products are being developed. The methodology developed in this programme is designed to reliably secure a short and convergent synthesis of any given polypropionate or polyacetate sequence and thus should have general utility. Recent targets have included both terrestrial and marine natural products, leading to the completion of several total syntheses (concanamycin F, oleandomycin, elaiolide, ACRL Toxin IIIB, restricticin, denticulatin A and B, muamvatin, ebelactone A and B, tetrahydrolipstatin). Current targets include antibiotics (oasomycin A), vacuolar ATPase inhibitors (bafilomycin A1), antifungal agents (roxaticin), squalene synthase inhibitors (zaragozic acids) and siphonariid metabolites (siphonarin B).

discodermolide, peloruside A, laulimalide, callipetoside

Selected publications

  1. Paterson, I.; Doughty, V. A.; McLeod, M. D.; Trieselmann, T. Total synthesis of (+)-concanamycin F. Angew. Chem. Int. Ed. 2000, 39, 1308.
  2. Paterson, I.; Lombart, H.-G.; Allerton, C. Total synthesis of elaiolide using a copper(I)-promoted Stille cyclodimerization reaction. Org. Lett. 1999, 1, 19.
  3. Paterson, I.; Hulme, A. N. Total synthesis of (—)-ebelactone A and B. J. Org. Chem. 1995, 60, 3288.
  4. Paterson, I.; Norcross, R. D.; Ward, R. A.; Romea, P.; Lister, M. A. Studies in macrolide synthesis. Synthesis of oleandolide using substrate- and reagent-controlled aldol reactions of (S)-1-(benzyloxy)-2-methylpentan-3-one. J. Am. Chem. Soc. 1994, 116, 11287.
  5. Paterson, I; Perkins, M. V. Total synthesis of the marine polypropionate (+)-muamvatin. A configurational model for Siphonariid metabolites. J. Am. Chem. Soc. 1993, 115, 1608.

Current Projects

  1. Synthesis of Bioactive Marine Metabolides.
  2. New Methods for the Synthesis of Polyketide Natural Products.
  3. Expanding Polyketide Diversity.
  4. New Reagents for Asymmetric Aldol Reactions.
  5. Biomimetic Total Synthesis of Polyether Ionophores.
  6. Designed Synthesis of Lophotoxin Analogues.
  7. Designed Synthesis of Novel Macrolide Antibiotics Related to Erythromycin.
  8. Transition State Modelling of Reactions (with Dr J. M. Goodman and Prof C. Gennari)