Department of Chemistry, University of Durham
Dr. Patrick G. Steel
Telephone: 0191 374 3131 (direct)
All of our research come under the general heading of organic synthesis. This includes target synthesis of structurally interesting biologically active natural and unnatural molecules, and the development of new synthetic methodology. In particular, we place an emphasis on achieving a high degree of control of both the regiochemistry and stereochemistry (in particular enantioselectivity).Throughout the work a wide range of hands-on experimental techniques (NMR, GCMS, FTIR, HPLC, GLC, optical rotation) are used to assay chemical and enantiomeric purity. Crystallographic data is obtained through collaboration with Professor Howard's groups whilst other interactions exists throught the department notably with the organometallic and polymer research groups. The work is currently supported by both the EPSRC and industry including Glaxo-Wellcome, Merck, Rhone Poulenc and Zeneca.
More specifically current interests include:
- The total synthesis of the diterpene vinigrol (A). This natural product contains a unique butanodecalin skeleton (bridged eight membered ring) whilst also possessing considerable anti-hypertensive properties. This synthesis is also being used for the development of a new range of enantioselective substituted ketene equivalents
- Synthesis of structural analogues of the squalene-synthase inhibitor, squalestatin (B). In addition to its unusual tricarboxylic acid core this natural product is a potent inhibitor of cholesterol biosynthesis. However, since the natural product also exhibits toxic side effects all analogues are of considerable pharmaceutical interest especially those which reveal information as to the structure of the enzyme binding site and this is an area of particular interest. Again our synthetic strategy has a basis in the development of new synthetic methodology. In this case the design of chiral Lewis acids for the enantioselective cleavage of cyclic acetals.
- An approach to the unusual 'inside-outside' bridged ring skeleton of the tumour promoting diterpene ingenol (C). Our synthetic strategy involves exploration of the potential of a tandem Birch reduction-divinylcyclopropyl rearrangement sequence followed by a putative biomimetic Wagner-Meerwein/pinacol skeletal rearrangement.
- Silicon based reagents are becoming increasingly common in organic synthesis although their use in asymmetric synthesis is limited by the lack of efficient methods for the preparation of configurationally stable chiral silanes. We have initiated a program to synthesise a variety of enantiomerically pure cyclic organosilanes and study their application as chiral auxiliaries and chiral resolving agents. Similarly silenes (compounds containing a carbon silicon double bond) have not been explored in synthesis. We are undertaking a systematic survey of the reactions of differently functionalised silenes with a particular emphasis on stereoselectivity and the subsequent elaboration of the silacyclic adducts.
We are also interested in the use of simple carbohydrate building blocks in cationic polymerisation processes. The high degree of asymmetric functionality available in the sugar monomer permits the construction of a polymer chain with high stereocontrol (in the primary, secondary and tertiary structure) that is both readily functionalised and potentially biodegradeable. The work includes both small molecule asymmetric synthesis and the development of an efficient polymerisation process. Currently we have established a highly stereoselective dimerisation process for cyclic vinyl ethers and are currently extending this work to higher oligomers.
Other areas of study are principally involved in the development of new methods in asymmetric synthesis. These include asymmetric organolanthanide reagents, new chiral Lewis acid methodology, chiral ketene reagents and phosphorus based chiral auxiliaries.
- J. L. Matthews and P. G. Steel, 'Ligand Controlled Diastereoselectivity in the Rhodium Catalysed Hydroboration of Divinylsilanes' Tetrahedron Lett., 1994, 1421.
A. S. Batsanov, I. M. Clarkson, J. A. K. Howard and P. G. Steel, 'Silenes in Organic Synthesis 1: Diastereoselectivity in the Siloxysilene-Diene Diels-Alder Cycloaddition', Tetrahedron Lett., 1996, 2491.
A. S. Batsanov, A. L. J. Byerley, J. A. K. Howard and P. G. Steel, 'Chiral Auxiliaries in the Vinyl Epoxide-Dihydrofuran Rearrangement', Synlett , 1996, 401.
A. L. J. Byerley and P. G. Steel, C-C Disaccharides via the Efficient Highly Stereoselective Dimerisation Of Glycals, Tetrahedron Lett., 1996, submitted for publication.
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This page last modified December 16th,
1996 by Andrew Hughes