Anthony Gerard Martin Barrett | |
---|---|
Born | |
Nationality | British, US |
Alma mater | Imperial College London |
Scientific career | |
Institutions | Northwestern University, Colorado State University, Imperial College London |
Doctoral advisor | Derek Barton |
Doctoral students | Matthew Fuchter |
Website | www |
Anthony Gerard Martin Barrett is a British chemist, and Sir Derek Barton Professor of Synthesis, Glaxo Professor of Organic Chemistry at Imperial College London. He is Director of the Wolfson Centre for Organic Chemistry in Medical Science. [1] He was elected a fellow of the Royal Society in 1999 [2] and Academy of Medical Sciences in 2003. He obtained a BSc as well as PhD from Imperial College London in 1973 and 1975 respectively.
Barrett was educated at Heles Grammar School in Exeter. He attended Imperial College, London (1st Class Honours BSc in 1973 and DIC and PhD in 1975). He carried out his Ph.D. working under the direction of Sir Derek Barton, Nobel Laureate.
Barrett was appointed lecturer in organic chemistry (1975) at IC and senior lecturer (1982). In 1983, he was appointed full professor of Chemistry at Northwestern University in Evanston, Illinois, and in 1990 moved to Colorado State University. After ten years research in the US, he returned to IC as Glaxo Professor of Organic Chemistry, Director of the Wolfson Centre for Organic Chemistry in Medical Science and Head of the Organic Section. He was appointed the Sir Derek Barton Professor of Synthetic Chemistry in 1999. Barrett has invented many reactions including novel glycosidations, atom-economic aromatic substitution reactions, metal-catalyzed oxidations and hydroaminations, reactions using ROMP-gel supported reagents and multi-component benzyne coupling reactions. He has contributed extensively to the synthesis of β-lactams using alkenyl anions, ynolates, novel isocyanates, iron vinylidines, heteroatom functionalized nitroalkenes, and ring closing alkene and enyne metathesis reactions. He has completed the total synthesis of diverse bioactive natural products including papulacandin D, papuamine, showdomycin, milbemycin β3, the palmarumycins and preussomerin G, [3] (+)-calyculin A [4] and the multiple cyclopropane CETP inhibitor U-106305 and structurally related cyclopropane nucleoside FR-900848 [5] and coronanes. He has also published highly flexible methods for the biomimetic total syntheses of resorcylate and meroterpenoid natural products including 15G256β, [6] aigialomycin D, [7] LL-Z1640-2, [8] cruentaren A, [9] hericenone J [10] and macrosporin, [11] amorphastilbol, [12] (+)-hongoquercin A and B, [13] and austalides. [14] Barrett, in collaboration with Brian M. Hoffman at Northwestern University, has published pioneering work on the synthesis of diverse porphyrazines bearing 8, 6, 4, and 2 thiols, amines or alcohols as peripheral macrocyclic ring substituents and the conversion of these polydentate ligands by the complexation of metal ions both within the macrocyclic cavity and at the periphery to produce diverse multimetallic complexes. [15] [16] Several such complexes are imaging agents for the highly selective detection of cancers in both cells and in vivo and as PDT agents. [17] [18] [19] [20] Additionally, Barrett in collaboration with Simak Ali and R. Charles Coombes in Medicine at Imperial College and Dennis Liotta and James P. Snyder in Emory University has made pioneering contributions to addressing unmet medical need with the invention of highly selective and bioavailable inhibitors of the Cyclin Dependent Kinases including CDK-7 inhibitor ICEC0942 (CT7001), which have been licensed by Carrick Therapeutics for clinical trials to treat Tamoxifen-resistant and other cancers. [21] [22] [23]
Barrett was the first to demonstrate the increased stability of per-alkylated aza crown ether analogues under dissolving metal reduction conditions. [24] This not only triggered the development of thermally stable solid alkalides [25] [26] and electrides [27] ), but also led him and his doctoral student René Riedel, in a multidisciplinary approach and in collaboration with Peter Edwards, to provide compelling experimental evidence for the predominant formation of alkalide ion pairs in solution for the first time. [28]
Barrett has received numerous awards for his contributions to research from the Royal Society of Chemistry (1980 Meldola Medal, [29] 1982 Harrison Medal , 1986 Corday-Morgan Medal , 1994 Tilden Lectureship, [30] 1996 Award in Synthetic Organic Chemistry, 2001 Award in Natural Products Chemistry, 2004 Pedler Lectureship, [31] 2005 Simonsen Lectureship, [32] 2010 Charles Rees Award [33] ), the American Chemical Society (1986 Cope Scholar Award), the Royal Society (2002 Royal Society Wolfson Research Merit Award ), Imperial College (1981 Armstrong Medal), the Camille and Henry Dreyfus Foundation (1987 Teacher Scholar Award ), Glaxo GlaxoSmithKline Wellcome (2000 Award for Innovative Chemistry), Institute of Applied Catalysis (2001 Award for Innovation in Applied Catalysis), and the Specialised Organic Sector Association (2000 Innovation Award). In 2017 he received the Imperial College President's Medal for Excellence in Research: Excellence in Innovation and Entrepreneurship (with Simak Ali, R. Charles Coombes and Matthew Fuchter).
In organic chemistry, allenes are organic compounds in which one carbon atom has double bonds with each of its two adjacent carbon atoms. Allenes are classified as cumulated dienes. The parent compound of this class is propadiene, which is itself also called allene. A group of the structure R2C=C=CR− is called allenyl, while a substituent attached to an allene is referred to as an allenic substituent. In analogy to allylic and propargylic, a substituent attached to a saturated carbon α to an allene is referred to as an allenylic substituent. While allenes have two consecutive ('cumulated') double bonds, compounds with three or more cumulated double bonds are called cumulenes.
In organic chemistry, an imine is a functional group or organic compound containing a carbon–nitrogen double bond. The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bonds. Imines are common in synthetic and naturally occurring compounds and they participate in many reactions.
The Fischer indole synthesis is a chemical reaction that produces the aromatic heterocycle indole from a (substituted) phenylhydrazine and an aldehyde or ketone under acidic conditions. The reaction was discovered in 1883 by Emil Fischer. Today antimigraine drugs of the triptan class are often synthesized by this method.
Aromatization is a chemical reaction in which an aromatic system is formed from a single nonaromatic precursor. Typically aromatization is achieved by dehydrogenation of existing cyclic compounds, illustrated by the conversion of cyclohexane into benzene. Aromatization includes the formation of heterocyclic systems.
In organic chemistry, a cyclophane is a hydrocarbon consisting of an aromatic unit and a chain that forms a bridge between two non-adjacent positions of the aromatic ring. More complex derivatives with multiple aromatic units and bridges forming cagelike structures are also known. Cyclophanes are well-studied examples of strained organic compounds.
Pentacene is a polycyclic aromatic hydrocarbon consisting of five linearly-fused benzene rings. This highly conjugated compound is an organic semiconductor. The compound generates excitons upon absorption of ultra-violet (UV) or visible light; this makes it very sensitive to oxidation. For this reason, this compound, which is a purple powder, slowly degrades upon exposure to air and light.
In organic chemistry, a phosphite ester or organophosphite usually refers to an organophosphorous compound with the formula P(OR)3. They can be considered as esters of an unobserved tautomer phosphorous acid, H3PO3, with the simplest example being trimethylphosphite, P(OCH3)3. Some phosphites can be considered esters of the dominant tautomer of phosphorous acid (HP(O)(OH)2). The simplest representative is dimethylphosphite with the formula HP(O)(OCH3)2. Both classes of phosphites are usually colorless liquids.
The Negishi coupling is a widely employed transition metal catalyzed cross-coupling reaction. The reaction couples organic halides or triflates with organozinc compounds, forming carbon-carbon bonds (C-C) in the process. A palladium (0) species is generally utilized as the catalyst, though nickel is sometimes used. A variety of nickel catalysts in either Ni0 or NiII oxidation state can be employed in Negishi cross couplings such as Ni(PPh3)4, Ni(acac)2, Ni(COD)2 etc.
Zoltan George Hajos was a Hungarian-American organic chemist. Originally an academic in his native Budapest, then an industrial chemist in the pharmaceutical industry, he is known for the Hajos–Parrish–Eder–Sauer–Wiechert reaction.
Synthesis of morphine-like alkaloids in chemistry describes the total synthesis of the natural morphinan class of alkaloids that includes codeine, morphine, oripavine, and thebaine and the closely related semisynthetic analogs methorphan, buprenorphine, hydromorphone, hydrocodone, isocodeine, naltrexone, nalbuphine, oxymorphone, oxycodone, and naloxone.
Lavendamycin is a naturally occurring chemical compound discovered in fermentation broth of the soil bacterium Streptomyces lavendulae. Lavendamycin has antibiotic properties and anti-proliferative effects against several cancer cell lines. The use of lavendamycin as a cytotoxic agent in cancer therapy failed due to poor water solubility and non-specific cytotoxicity. The study of lavendamycin-based analogs designed to overcome these liabilities has been an area of research.
Biomimetic synthesis is an area of organic chemical synthesis that is specifically biologically inspired. The term encompasses both the testing of a "biogenetic hypothesis" through execution of a series of reactions designed to parallel the proposed biosynthesis, as well as programs of study where a synthetic reaction or reactions aimed at a desired synthetic goal are designed to mimic one or more known enzymic transformations of an established biosynthetic pathway. The earliest generally cited example of a biomimetic synthesis is Sir Robert Robinson's organic synthesis of the alkaloid tropinone.
Lactimidomycin is a glutarimide antibiotic derived from the bacteria Streptomyces amphibiosporus. It has antifungal, antiviral and anti-cancer properties, acting as a direct inhibitor of protein translation in ribosomes. Antiviral activity is seen against a variety of RNA viruses including flaviviruses such as dengue fever, Kunjin virus and Modoc virus, as well as vesicular stomatitis virus and poliovirus. As lactimidomycin is a natural product containing an unusual unsaturated 12-membered lactone ring, it has been the subject of numerous total synthesis approaches.
Peter Wipf is a distinguished university professor of chemistry at the University of Pittsburgh. His research interests focus on the total synthesis of natural products, the discovery of new transformations of strained molecules, and the development of new pharmaceuticals. He is a Fellow of the Royal Society of Chemistry (RSC), the American Association for the Advancement of Science (AAAS), and the American Chemical Society (ACS).
MoOPH, also known as oxodiperoxymolybdenum(pyridine)-(hexamethylphosphoric triamide), is a reagent used in organic synthesis. It contains a molybdenum(VI) center with multiple oxygen ligands, coordinated with pyridine and HMPA ligands, although the HMPA can be replaced by DMPU. It is an electrophilic source of oxygen that reacts with enolates and related structures, and thus can be used for alpha-hydroxylation of carbonyl-containing compounds. Other reagents used for alpha-hydroxylation via enol or enolate structures include Davis oxaziridine, oxygen, and various peroxyacids. This reagent was first utilized by Edwin Vedejs as an efficient alpha-hydroxylating agent in 1974 and an effective preparative procedure was later published in 1978.
Organotantalum chemistry is the chemistry of chemical compounds containing a carbon-to-tantalum chemical bond. A wide variety of compound have been reported, initially with cyclopentadienyl and CO ligands. Oxidation states vary from Ta(V) to Ta(-I).
Mark S. Cushman is an American chemist, whose primary research is in the area of medicinal chemistry. He completed his pre-pharmacy studies at Fresno State College (now California State University, Fresno) in 1965. He then attended the University of California San Francisco (as a University of California Regents Scholar), earning a Pharm.D. in 1969 and a Ph.D. in Medicinal Chemistry in 1973. Thereafter, he performed postdoctoral training in the laboratory of George Büchi, Ph.D., at the Massachusetts Institute of Technology (MIT). There, his research focused on the discovery and development of new synthetic methodologies, and the isolation and structural characterization of mycotoxins from Aspergillus niger. In 1975, he joined the Department of Medicinal Chemistry and Molecular Pharmacology (at the time, Department of Medicinal Chemistry and Pharmacognosy) at Purdue University. From 1983 to 1984, Prof. Cushman was a Senior Fulbright Scholar at Munich Technical University working in the laboratory of Professor Adelbert Bacher. His sabbatical work dealt with the design and synthesis of probes to elucidate key aspects of the biosynthesis of riboflavin (vitamin B2). Currently he holds the rank of Distinguished Professor Emeritus of Medicinal Chemistry at Purdue University. He has mentored 40 graduate students, 59 postdoctoral researchers, and 5 visiting scholars. He has published 348 papers and holds 41 patents. His work has ~17,000 citations with an h-index of 69. His most cited papers had 471, 403, and 299 citations as of August 2021. He has made seminal contributions to the fields of synthetic and medicinal chemistry including the development of new synthetic methodologies, the synthesis of natural products, and the preparation of antivirals, antibacterials, and anticancer agents, and mechanism probes to understand the function of over thirty macromolecular targets. One of his main scientific contributions is the development of the indenoisoquinolines, molecules that inhibit the action of toposiomerase I (Top1) and stabilize the G-quadruplex in the Myc promoter. Three indenoisoquinolines designed and synthesized by his research group at Purdue University [indotecan (LMP 400), indimitecan (LMP 776), and LMP 744] demonstrated potent anticancer activity in vivo and have completed phase I clinical trials at the National Institutes of Health.
A phosphetane is a 4-membered organophosphorus heterocycle. The parent phosphetane molecule, which has the formula C3H7P, is one atom larger than phosphiranes, one smaller than phospholes, and is the heavy-atom analogue of azetidines. The first known phosphetane synthesis was reported in 1957 by Kosolapoff and Struck, but the method was both inefficient and hard to reproduce, with yields rarely exceeding 1%. A far more efficient method was reported in 1962 by McBride, whose method allowed for the first studies into the physical and chemical properties of phosphetanes. Phosphetanes are a well understood class of molecules that have found broad applications as chemical building blocks, reagents for organic/inorganic synthesis, and ligands in coordination chemistry.
Matthew John Fuchter is a British chemist who is a Professor of Chemistry at the University of Oxford. His research focuses on the development and application of novel functional molecular systems to a broad range of areas; from materials to medicine. He has been awarded both the Harrison-Meldola Memorial Prize (2014) and the Corday–Morgan Prizes (2021) of the Royal Society of Chemistry. In 2020 he was a finalist for the Blavatnik Awards for Young Scientists.
T.V. (Babu) RajanBabu is an organic chemist who holds the position of Distinguished Professor of Chemistry in the College of Arts and Sciences at the Ohio State University. His laboratory traditionally focuses on developing transition metal-catalyzed reactions. RajanBabu is known for helping develop the Nugent-RajanBabu reagent, a chemical reagent used in synthetic organic chemistry as a single electron reductant.