Imperial College London

Professor A G M Barrett, FRS, FMedSci

Faculty of Natural SciencesDepartment of Chemistry

Head of Synthesis
 
 
 
//

Contact

 

+44 (0)20 7594 5766agm.barrett

 
 
//

Assistant

 

Ms Virginia Manch +44 (0)20 7594 5767

 
//

Location

 

733ChemistrySouth Kensington Campus

//

Summary

 

Publications

Publication Type
Year
to

470 results found

Almond-Thynne J, White AJP, Polyzos A, Rzepa HS, Parsons PJ, Barrett AGM, Almond-Thynne J, White AJP, Polyzos A, Rzepa H, Parsons P, Barrett AGMet al., 2017, Synthesis and Reactions of Benzannulated Spiroaminals: Tetrahydrospirobiquinolines, ACS Omega, Vol: 2, Pages: 3241-3249, ISSN: 2470-1343

An efficient two-step synthesis of symmetrical and unsymmetrical tetrahydrospirobiquinolines from o-azidobenzaldehydes is reported. A novel series of tetrahydrospirobiquinolines was prepared by sequential double-aldol condensation with acetone, cyclopentanone, and cyclohexanone to form the corresponding o,o′-diazido-dibenzylidene-acetone, -cyclopentanone, and -cyclohexanone derivatives, respectively, and hydrogenation–spirocyclization. The spirodiamines were further derivatized by electrophilic aromatic bromination, Suzuki coupling, and N-alkylation, all of which proceeded with preservation of the spirocyclic core.

JOURNAL ARTICLE

Hazel P, Kroll SHB, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AGM, Freemont PS, Hazel P, Kroll SHB, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AGM, Freemont PS, Hazel P, Kroll SHB, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AGM, Freemont PS, Hazel P, Kroll SHB, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AGM, Freemont PS, Hazel P, Kroll SHB, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AGM, Freemont PS, Hazel P, Kroll SH, Bondke A, Barbazanges M, Patel H, Fuchter MJ, Coombes RC, Ali S, Barrett AG, Freemont PSet al., 2017, Inhibitor Selectivity for Cyclin-Dependent Kinase7: AStructural, Thermodynamic, and Modelling Study, CHEMMEDCHEM, Vol: 12, Pages: 372-380, ISSN: 1860-7179

Deregulation of the cell cycle by mechanisms that lead to elevated activities of cyclin-dependent kinases (CDK) is a feature of many human diseases, cancer in particular. We identified small-molecule inhibitors that selectively inhibit CDK7, the kinase that phosphorylates cell-cycle CDKs to promote their activities. To investigate the selectivity of these inhibitors we used a combination of structural, biophysical, and modelling approaches. We determined the crystal structures of the CDK7-selective compounds ICEC0942 and ICEC0943 bound to CDK2, and used these to build models of inhibitor binding to CDK7. Molecular dynamics (MD) simulations of inhibitors bound to CDK2 and CDK7 generated possible models of inhibitor binding. To experimentally validate these models, we gathered isothermal titration calorimetry (ITC) binding data for recombinant wild-type and binding site mutants of CDK7 and CDK2. We identified specific residues of CDK7, notably Asp155, that are involved in determining inhibitor selectivity. Our MD simulations also show that the flexibility of the G-rich and activation loops of CDK7 is likely an important determinant of inhibitor specificity similar to CDK2.

JOURNAL ARTICLE

Kandela IK, McAuliffe KJ, Cochran LE, Barrett AGM, Hoffman BM, Mazar AP, Trivedi ER, Kandela IK, McAuliffe KJ, Cochran LE, Barrett AGM, Hoffman BM, Mazar AP, Trivedi ER, Kandela IK, McAuliffe KJ, Cochran LE, Barrett AGM, Hoffman BM, Mazar AP, Trivedi ERet al., 2017, Discovery of the Antitumor Effects of a Porphyrazine Diol (Pz 285) in MDA-MB-231 Breast Tumor Xenograft Models in Mice., ACS Med Chem Lett, Vol: 8, Pages: 705-709, ISSN: 1948-5875

A series of porphyrazines (Pzs) with chiral bis-acetal moieties in the β-pyrrole positions ((2R,3R)-2,3-dimethyl-2,3-dimethoxy-1,4-diox-2-ene) have been synthesized and screened as antitumor agents in MDA-MB-231 breast tumor cells in vitro. The lead Pz 285 was further tested in a mouse tumor xenograft model with Td-tomato-luc2 fluorescent breast tumor cells (MDA-MB-231 LM24 Her2+) that are highly metastatic to the lungs. Pz 285 shows marked antitumor effects in vivo, with treated mice exhibiting longer median survival that we attribute to smaller primary tumor regrowth after resection and less occurrence of metastasis when compared to vehicle control groups. Pz 285 is further compared to the clinically approved chemotherapeutic doxorubicin (Dox). This report lays the groundwork for development of an understudied class of compounds for classical chemotherapy.

JOURNAL ARTICLE

Ma T-K, White AJP, Barrett AGM, Ma T-K, White AJP, Barrett AGM, Ma TK, White AJP, Barrett AGMet al., 2017, Meroterpenoid total synthesis: Conversion of geraniol and farnesol into amorphastilbol, grifolin and grifolic acid by dioxinone-beta-keto-acylation, palladium catalyzed decarboxylative allylic rearrangement and aromatization, TETRAHEDRON LETTERS, Vol: 58, Pages: 2765-2767, ISSN: 0040-4039

Biomimetic total syntheses of resorcinols amorphastilbol, grifolin and grifolic acid have been completed in four steps starting from geraniol and farnesol without the use of phenolic protection. The key steps involve C-acylation of dioxinone-β-keto esters, followed by palladium catalyzed decarboxylative allylic rearrangement and biomimetic aromatization.

JOURNAL ARTICLE

Ali S, Patel H, Periyasamy M, Bondke A, Slafer BW, Ottaviani S, Harrod A, Buluwela L, Fuchter MJ, Barrett AGM, Coombes RC, Ali S, Patel H, Periyasamy M, Bondke A, Slafer BW, Ottaviani S, Harrod A, Buluwela L, Fuchter MJ, Barrett AGM, Coombes RCet al., 2016, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for breast cancer, UK Breast Cancer Research Symposium, Publisher: SPRINGER, Pages: 195-195, ISSN: 0167-6806

CONFERENCE PAPER

Elliott DC, Ma T-K, Selmani A, Cookson R, Parsons PJ, Barrett AGM, Elliott DC, Ma T-K, Selmani A, Cookson R, Parsons PJ, Barrett AGM, Elliott DC, Ma T-K, Selmani A, Cookson R, Parsons PJ, Barrett AGM, Elliott DC, Ma T-K, Selmani A, Cookson R, Parsons PJ, Barrett AGM, Barrett AGM, Elliott D, Ma T, Cookson R, Parsons P, Selmani Aet al., 2016, Sequential Ketene Generation from Dioxane-4,6-dione-keto-dioxinones for the Synthesis of Terpenoid Resorcylates, ORGANIC LETTERS, Vol: 18, Pages: 1800-1803, ISSN: 1523-7060

Trapping of the ketene generated from the thermolysis of 2-methyl-2-phenyl-1,3-dioxane-4,6-dione-keto-dioxinone at 50 °C with primary, secondary, or tertiary alcohols gave the corresponding dioxinone β-keto-esters in good yield under neutral conditions. These intermediates were converted by palladium(0)-catalyzed decarboxylative allyl migration and aromatization into the corresponding β-resorcylates. These transformations were applied to the syntheses of the natural products (±)-cannabiorcichromenic and (±)-daurichromenic acid.

JOURNAL ARTICLE

Cookson R, Barrett TN, Barrett AGM, Cookson R, Barrett TN, Barrett AGM, Cookson R, Barrett TN, Barrett AGM, Cookson R, Barrett TN, Barrett AGMet al., 2015, beta-Keto-dioxinones and beta,delta-Diketo-dioxinones in Biomimetic Resorcylate Total Synthesis, ACCOUNTS OF CHEMICAL RESEARCH, Vol: 48, Pages: 628-642, ISSN: 0001-4842

Resorcylates are a large group of bioactive natural products that are biosynthesized from acetate and malonate units via the intermediacy of polyketides. These polyketides undergo cyclization reactions to introduce the aromatic core. The bioactivities of the resorcylates including resorcylate macrocyclic lactones include anticancer, antimalarial, mycotoxicity, antifungal, and antibiotic properties, and several compounds in the series are already in use in medicine. Examples are prodrugs derived from mycophenolic acid as immunosuppressants and the Hsp-90 inhibitor, AT13387, which is in phase-II clinical trials for the treatment of small cell lung cancer and melanoma. In consequence of these biological activities, methods for the concise synthesis of diverse resorcylates are of considerable importance. In natural product chemistry, biomimetic total synthesis can have significant advantages including functional group tolerance in key steps, the minimization of the use of protection and deprotection reactions and the shortening of the total number of synthetic steps. This Account provides a description of our adaption of the dioxinone chemistry of Hyatt, Clemens, and Feldman for the synthesis and retro-Diels-Alder reactions of diketo-dioxinones. Such dioxinones, which were synthesized by a range of C-acylation reactions, were found to undergo retro-Diels-Alder reactions on heating to provide the corresponding triketo-ketenes with the loss of acetone. The ketene reactive intermediates were rapidly trapped both inter- and intramolecularly with alcohols to provide the corresponding β,δ,ζ-triketo-esters. These compounds, which consist of keto-enol mixtures, readily undergo cycloaromatization to produce resorcylate esters and macrocyclic lactones. We have established the use of diketo-dioxinones as key general intermediates for the synthesis of diverse resorcylate natural products and for the synthesis of new classes of compounds for the generation of medicin

JOURNAL ARTICLE

Doepner AM, Aboagye EO, Barrett AGM, Doepner AM, Aboagye EO, Barrett AGMet al., 2015, 2 '-Deoxy-2 ',2 '-difluorothymidine analogues for radiolabeling with fluorine-18 and other biomedical applications, TETRAHEDRON LETTERS, Vol: 56, Pages: 3293-3297, ISSN: 0040-4039

JOURNAL ARTICLE

Palma A, Serginson JM, Barrett AGM, Palma A, Serginson JM, Barrett AGMet al., 2015, Synthesis of poly beta ketoesters via double acylketene trapping, TETRAHEDRON LETTERS, Vol: 56, Pages: 674-676, ISSN: 0040-4039

JOURNAL ARTICLE

Anderson K, Laclef S, Barrett AGM, Anderson K, Laclef S, Barrett AGMet al., 2014, Mechanistic studies of highly regioselective decarboxylative-prenyl migration reactions of prenyloxycarbonyl-diketo-dioxinones, TETRAHEDRON, Vol: 70, Pages: 5569-5579, ISSN: 0040-4020

JOURNAL ARTICLE

Barrett TN, Barrett AGM, Barrett TN, Barrett AGM, Barrett TN, Barrett AGM, Barrett TN, Barrett AGMet al., 2014, Cascade Polyketide and Polyene Cyclizations: Biomimetic Total Synthesis of Hongoquercin B, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 136, Pages: 17013-17015, ISSN: 0002-7863

The total synthesis of hongoquercin B was carried out in 9 steps from trans,trans-farnesyl acetate using a palladium catalyzed decarboxylative π-farnesyl rearrangement of a diketo-dioxinone ester, aromatization and cationic diene-epoxide cyclization as key steps. This cascade tetracyclization simplifies the synthesis of terpenoid resorcylate natural products.

JOURNAL ARTICLE

Barrett TN, Patel BH, Barrett AGM, Barrett TN, Patel BH, Barrett AGMet al., 2014, Synthesis of C-5-substituted resorcylates and resorcinamides via formylation-aromatization of functionalized keto-dioxinones, TETRAHEDRON, Vol: 70, Pages: 6894-6901, ISSN: 0040-4020

JOURNAL ARTICLE

Blencowe PS, Barrett AGM, Blencowe PS, Barrett AGMet al., 2014, Biomimetic Synthesis of Functionalized gamma-Resorcylates from Dioxinone Derivatives, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2014, Pages: 4844-4853, ISSN: 1434-193X

JOURNAL ARTICLE

Brookes PA, Barrett AGM, Brookes PA, Barrett AGM, Brookes PA, Barrett AGM, Brookes PA, Barrett AGMet al., 2014, Iodoaromatization Reactions of Enyne-Dioxinones: Syntheses of 4H-1,3-Benzodioxin-4-ones, Masked Pentasubstituted Arenes, JOURNAL OF ORGANIC CHEMISTRY, Vol: 79, Pages: 8706-8714, ISSN: 0022-3263

Sequential reaction of a keto-dioxinone with dimethylformamide dimethyl acetal and a range of magnesium acetylides gave the corresponding enyne-dioxinones as mixtures of E and Z isomers (E > Z). Subsequent reaction with iodine monochloride resulted in cycloaromatization, presumably via an iodovinyl cation, giving a range of 4H-1,3-benzodioxin-4-ones.

JOURNAL ARTICLE

Cookson R, Poeverlein C, Lachs J, Barrett AGM, Cookson R, Pöverlein C, Lachs J, Barrett AGMet al., 2014, Synthetic Studies towards Radicicol through Biomimetic Macrolactonization and Transannular Aromatization Reactions, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2014, Pages: 4523-4535, ISSN: 1434-193X

JOURNAL ARTICLE

Kim M-S, Buisson LA, Heathcote DA, Hu H, Braddock DC, Barrett AGM, Ashton-Rickardt PG, Snyder JP, Kim M-S, Buisson LA, Heathcote DA, Hu H, Braddock DC, Barrett AGM, Ashton-Rickardt PG, Snyder JP, Kim M-S, Buisson LA, Heathcote DA, Hu H, Braddock DC, Barrett AGM, Ashton-Rickardt PG, Snyder JP, Kim M-S, Buisson LA, Heathcote DA, Hu H, Braddock DC, Barrett AGM, Ashton-Rickardt PG, Snyder JPet al., 2014, Approaches to design non-covalent inhibitors for human granzyme B (hGrB), ORGANIC & BIOMOLECULAR CHEMISTRY, Vol: 12, Pages: 8952-8965, ISSN: 1477-0520

A structure-based design campaign for non-covalent small molecule inhibitors of human granzyme B was carried out by means of a virtual screening strategy employing three constraints and probe site-mapping with FTMAP to identify ligand "hot spots". In addition, new scaffolds of diverse structures were subsequently explored with ROCS shape-based superposition methods, following by Glide SP docking, induced fit docking and analysis of QikProp molecular properties. Novel classes of moderately active small molecule blockers (≥25 μM IC50 values) from commercially available libraries were identified, and three novel scaffolds have been synthesized by multi-step procedures. Furthermore, we provide an example of a comprehensive structure-based drug discovery approach to non-covalent inhibitors that relies on the X-ray structure of a covalently bound ligand and suggest that the design path may be compromised by alternative and unknown binding poses.

JOURNAL ARTICLE

Loerbroks C, Boeker B, Cordes J, Barrett AGM, Thiel W, Loerbroks C, Böker B, Cordes J, Barrett AGM, Thiel Wet al., 2014, Spiroaminals - Crystal Structure and Computational Investigation of Conformational Preferences and Tautomerization Reactions, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2014, Pages: 5476-5486, ISSN: 1434-193X

JOURNAL ARTICLE

Reid S, Barrett AGM, Hill MS, Procopiou PA, Reid S, Barrett AGM, Hill MS, Procopiou PA, Reid S, Barrett AGM, Hill MS, Procopiou PA, Reid S, Barrett AGM, Hill MS, Procopiou PAet al., 2014, Heavier Alkaline Earth Catalyzed Ene-yne Cyclizations: Atom-Efficient Access to Tetrahydroisoquinoline Frameworks, ORGANIC LETTERS, Vol: 16, Pages: 6016-6019, ISSN: 1523-7060

Tetrahydroisoquinoline frameworks may be accessed with 100% atom efficiency through the alkaline earth catalyzed addition of primary amines to ene-yne substrates through a sequence of intermolecular alkene and intramolecular alkyne hydroamination steps.

JOURNAL ARTICLE

Trivedi ER, Ma Z, Waters EA, Macrenaris KW, Subramanian R, Barrett AGM, Meade TJ, Hoffman BM, Trivedi ER, Ma Z, Waters EA, Macrenaris KW, Subramanian R, Barrett AGM, Meade TJ, Hoffman BM, Trivedi ER, Ma Z, Waters EA, Macrenaris KW, Subramanian R, Barrett AGM, Meade TJ, Hoffman BM, Trivedi ER, Ma Z, Waters EA, Macrenaris KW, Subramanian R, Barrett AGM, Meade TJ, Hoffman BMet al., 2014, Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model, CONTRAST MEDIA & MOLECULAR IMAGING, Vol: 9, Pages: 313-322, ISSN: 1555-4309

Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1  = 11.5 mM(-1) s(-1)) that is approximately four times higher than that of a clinically used monomeric Gd(III) contrast agent, DOTA-Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu-Pz-Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg(-1) Cu-Pz-Gd(III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu-Pz-Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu-Pz-Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue.

JOURNAL ARTICLE

Brookes PA, Cordes J, White AJP, Barrett AGM, Brookes PA, Cordes J, White AJP, Barrett AGMet al., 2013, Total Synthesis of Mycophenolic Acid by a Palladium-Catalyzed Decarboxylative Allylation and Biomimetic Aromatization Sequence, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2013, Pages: 7313-7319, ISSN: 1434-193X

JOURNAL ARTICLE

Cordes J, Barrett AGM, Cordes J, Barrett AGMet al., 2013, Synthesis of Macrosporin and Related 9,10-Anthraquinones by Biomimetic Polyketide Aromatization and Cyclization of 6-Benzylresorcylates, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2013, Pages: 1318-1326, ISSN: 1434-193X

JOURNAL ARTICLE

Cordes J, Murray PRD, White AJP, Barrett AGM, Cordes J, Murray PRD, White AJP, Barrett AGM, Cordes J, Murray PRD, White AJP, Barrett AGM, Cordes J, Murray PRD, White AJP, Barrett AGMet al., 2013, 1,7-Diazaspiro[5.5]undecane - A Neglected Heterocycle, ORGANIC LETTERS, Vol: 15, Pages: 4992-4995, ISSN: 1523-7060

A convenient and simple three step synthesis of 1,7-diazaspiro[5.5]undecane via Claisen condensation and acid catalyzed decarboxylation and spirocyclization of N-Boc-δ-valerolactam is described. Reactions of this spiroaminal with electrophiles including alkyl halides, alkane dihalides, acid chlorides, and sulfonyl chlorides gave either spirocyclic adducts or tetrahydropyridine derivatives. Additionally, the parent heterocycle is a novel bidentate ligand and formed complexes with ruthenium(II) and copper(II).

JOURNAL ARTICLE

George NS, Anderson KE, Barrett AGM, George NS, Anderson KE, Barrett AGMet al., 2013, Total Synthesis of Cristatic Acid Based on Late-Stage Decarboxylative Allylic Migration and Biomimetic Aromatization of a Diketo Dioxinone, EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol: 2013, Pages: 7604-7610, ISSN: 1434-193X

JOURNAL ARTICLE

Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EO, Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EO, Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EO, Kaliszczak M, Patel H, Carroll L, Smith G, Delaney S, Heathcote DA, Coombes RC, Ali S, Aboagye EO, Kroll SHB, Bondke A, Fuchter MJ, Barrett AGM, Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EO, Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EO, Kaliszczak M, Patel H, Kroll SHB, Carroll L, Smith G, Delaney S, Heathcote DA, Bondke A, Fuchter MJ, Coombes RC, Barrett AGM, Ali S, Aboagye EOet al., 2013, Development of a cyclin-dependent kinase inhibitor devoid of ABC transporterdependent drug resistance, BRITISH JOURNAL OF CANCER, Vol: 109, Pages: 2356-2367, ISSN: 0007-0920

BACKGROUND: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy. METHODS: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy. RESULTS: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å(2)) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively. CONCLUSION: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.

JOURNAL ARTICLE

Miyatake-Ondozabal H, Barrett AGM, Miyatake-Ondozabal H, Barrett AGMet al., 2013, Synthetic studies towards tragoponol: preparation of a highly functionalized resorcylate, TETRAHEDRON LETTERS, Vol: 54, Pages: 4817-4820, ISSN: 0040-4039

JOURNAL ARTICLE

Blencowe PS, Barrett AGM, Blencowe PS, Barrett AGMet al., 2012, Synthesis of 6-substituted salicylates via biomimetic aromatization utilizing the cross metathesis of a vinyl dioxinone with homoallylic alcohols, CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, Vol: 90, Pages: 975-984, ISSN: 0008-4042

JOURNAL ARTICLE

Brinkmann C, Barrett AGM, Hill MS, Procopiou PA, Brinkmann C, Barrett AGM, Hill MS, Procopiou PA, Brinkmann C, Barrett AGM, Hill MS, Procopiou PA, Brinkmann C, Barrett AGM, Hill MS, Procopiou PAet al., 2012, Heavier Alkaline Earth Catalysts for the Intermolecular Hydroamination of Vinylarenes, Dienes, and Alkynes, JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, Vol: 134, Pages: 2193-2207, ISSN: 0002-7863

The heavier group 2 complexes [M{N(SiMe(3))(2)}(2)](2)(1, M = Ca; 2, M = Sr) and [M{CH(SiMe(3))(2)}(2)(THF)(2)] (3, M = Ca; 4, M = Sr) are shown to be effective precatalysts for the intermolecular hydroamination of vinyl arenes and dienes under mild conditions. Initial studies revealed that the amide precatalysts, 1 and 2, while compromised in terms of absolute activity by a tendency toward transaminative behavior, offer greater stability toward polymerization/oligomerization side reactions. In every case the strontium species, 2 and 4, were found to outperform their calcium congeners. Reactions of piperidine with para-substituted styrenes are indicative of rate-determining alkene insertion in the catalytic cycle while the ease of addition of secondary cyclic amines was found to be dependent on ring size and reasoned to be a consequence of varying amine nucleophilicity. Hydroamination of conjugated dienes yielded isomeric products via η(3)-allyl intermediates and their relative distributions were explained through stereoelectronic considerations. The ability to carry out the hydroamination of internal alkynes was found to be dramatically dependent upon the identity of the alkyne substituents while reactions employing terminal alkynes resulted in the precipitation of insoluble and unreactive group 2 acetylides. The rate law for styrene hydroamination with piperidine catalyzed by [Sr{N(SiMe(3))(2)}(2)](2) was deduced to be first order in [amine] and [alkene] and second order in [catalyst], while large kinetic isotope effects and group 2 element-dependent ΔS(++) values implicated the formation of an amine-assisted rate-determining alkene insertion transition state in which there is a considerable entropic advantage associated with use of the larger strontium center.

JOURNAL ARTICLE

Brinkmann C, Barrett AGM, Hill MS, Procopiou PA, Reidt S, Brinkmann C, Barrett AGM, Hill MS, Procopiou PA, Reid Set al., 2012, Alkaline Earth Catalysis of Alkynyl Alcohol Hydroalkoxylation/Cyclization, ORGANOMETALLICS, Vol: 31, Pages: 7287-7297, ISSN: 0276-7333

JOURNAL ARTICLE

Cordes J, Calo F, Anderson K, Pfaffeneder T, Laclef S, White AJP, Barrett AGM, Cordes J, Calo F, Anderson K, Pfaffeneder T, Laclef S, White AJP, Barrett AGM, Cordes J, Calo F, Anderson K, Pfaffeneder T, Laclef S, White AJP, Barrett AGM, Cordes J, Calo F, Anderson K, Pfaffeneder T, Laclef S, White AJP, Barrett AGMet al., 2012, Total Syntheses of Angelicoin A, Hericenone J, and Hericenol A via Migratory Prenyl- and Geranylation-Aromatization Sequences, JOURNAL OF ORGANIC CHEMISTRY, Vol: 77, Pages: 652-657, ISSN: 0022-3263

A five-step synthesis of the natural product angelicoin A using a late stage highly regioselective palladium(0)-catalyzed decarboxylative prenyl migration and aromatization sequence as the key step is reported. The method was extended with geranyl migration in eight-step total syntheses of hericenone J and hericenol A from geraniol.

JOURNAL ARTICLE

Cordes J, Laclef S, White AJP, Barrett AGM, Cordes J, Laclef S, White AJ, Barrett AG, Cordes J, Laclef S, White AJP, Barrett AGM, Cordes J, Laclef S, White AJP, Barrett AGMet al., 2012, Palladium(0)-Catalyzed Allylic Alkylation of Diketoester-Dioxinones with Allyl Acetates under Neutral Conditions: Synthesis of Hexasubstituted Benzene Derivatives, JOURNAL OF ORGANIC CHEMISTRY, Vol: 77, Pages: 3524-3530, ISSN: 0022-3263

Intermolecular palladium(0)-catalyzed allylic alkylation of diketoester-dioxinones was performed under neutral conditions with 2-alkenyl and 2-cycloalkenyl acetates. Subsequent aromatization using cesium carbonate gave rise to isopropylidene-protected hexasubstituted resorcylates.

JOURNAL ARTICLE

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00106001&limit=30&person=true