Coldham, Iain - University of Sheffield

个人简介

Professor Coldham obtained a BA in Chemistry from the University of Cambridge in 1986, followed by a PhD in 1989. After a postdoctoral research fellowship at the University of Texas at Austin (1989-1991), he was a member of staff at the University of Exeter as a Lecturer/Senior Lecturer from 1991 to 2003. In 2003 he became a Reader at the University of Sheffield, where he was promoted to Professor of Synthetic Organic Chemistry in 2008.

研究领域

New methodology in organic chemistry. Synthetic chemistry depends on reliable, high-yielding and selective reactions that access a wide variety of different structures. The discovery of new methods in synthesis is crucial to expand the range of novel compounds that can be made easily. Especially important is the development of new carbon-carbon bond-forming reactions. Our research group is studying the use of organometallic compounds in asymmetric synthesis, especially for carbon-carbon bond formation of nitrogen-containing compounds, prevalent in many biologically active molecules. We have founColdhamPicforWebd that 2-lithiopyrrolidines, piperidines and other cyclic amines undergo dynamic resolution in the presence of a chiral ligand (L*), leading to highly enantioenriched 2-substituted cyclic amine products. We have determined the kinetics of enantiomerization of several chiral organolithium compounds. Synthesis of biologically active compounds. We are using dipolar cycloaddition chemistry to access a variety of alkaloid structures. Intramolecular cycloadditions provide an efficient means to build up bicyclic and polycyclic ring systems in a rapid and stereocontrolled way. We have shown that this chemistry is applicable to the synthesis of the core ring system of the alkaloid manzamine A, which has significant biological activity (anti-cancer, anti-malarial, and other activity). One dipole that we use is an azomethine ylide, that we make by condensation of a secondary amine with an aldehyde. Intramolecular cycloaddition sets up two new rings and up to four new stereocentres in a single step. We have prepared simpler analogues of manzamine A and other heteroaromatic compounds to probe their biological activity. Recently, we have found that primary amines (such as amino-acids, amino-esters, hydroxylamine) can be used to condense with an aldehyde and promote a cascade process involving imine formation, cyclization, ylide formation and cycloaddition all in one pot. This chemistry provides an efficient method to prepare three rings directly from an acyclic aldehyde in a stereocontrolled way and has been applied to the total syntheses of several alkaloids (such as aspidospermidine, aspidospermine, quebrachamine and myrioxazine A).

近期论文

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Sadhukhan A, Hobbs MC, Meijer AJHM & Coldham I (2016) Highly enantioselective metallation–substitution alpha to a chiral nitrile. Chem. Sci.. View this article in WRRO Furnival R, Saruengkhanphasit R, Holberry H, Shewring J, Guerrand H, Adams H & Coldham I (2016) Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition. Org. Biomol. Chem.. View this article in WRRO Talk RA, Duperray A, Li X & Coldham I (2016) Synthesis of substituted tetrahydroisoquinolines by lithiation then electrophilic quench. Org. Biomol. Chem., 14(21), 4908-4917. View this article in WRRO Alkayar Z, Adams H & Coldham I (2016) Regiochemical and Stereochemical Studies of the Intramolecular Dipolar Cycloaddition of Nitrones Derived from Quaternary Aldehydes. Synlett, 27(03), 447-449. View this article in WRRO Gotham VJB, Hobbs MC, Burgin R, Turton D, Smythe C & Coldham I (2016) Synthesis and activity of a novel inhibitor of nonsense-mediated mRNA decay. Org. Biomol. Chem., 14(5), 1559-1563. View this article in WRRO Cochrane EJ, Hassall LA & Coldham I (2015) Preparation of 1-Substituted Tetrahydro-β-carbolines by Lithiation–Substitution. The Journal of Organic Chemistry, 80(11), 5964-5969. View this article in WRRO Pathak RB, Dobson BC, Ghosh N, Ageel KA, Alshawish MR, Saruengkhanphasit R & Coldham I (2015) Synthesis of the tricyclic core of manzamine A. Org. Biomol. Chem., 13(11), 3331-3340. View this article in WRRO Cochrane EJ, Leonori D, Hassall LA & Coldham I (2014) Synthesis and kinetic resolution of N-Boc-2-arylpiperidines. Chemical Communications, 50(69), 9910-9910. View this article in WRRO