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ABSTRACT: Simply aqueous sodium hydroxide is sufficient to exclude ionic side reactions and to prepare 2-aminobiphenyls from aryl diazotates and anilines through a new variant of the Gomberg-Bachmann reaction (see scheme). The metal-free reaction under basic conditions allows to exploit the highly radical-stabilizing effect of the aniline's free amino function for the first time, which leads to a so far unreached regioselectivity.
Chemistry 08/2012; 18(37):11555-9. · 5.93 Impact Factor
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ABSTRACT: Strategies for the identification of allosteric modulators of chemokine receptors largely rely on various cell-based functional assays. Radioligand binding assays are typically not available for allosteric binding sites. We synthesized, purified, and applied the first tritium-labeled allosteric modulator of the human chemokine receptor CXCR3 (RAMX3, [(3) H]N-{1-[3-(4-ethoxyphenyl)-4-oxo-3,4-dihydropyrido[2,3-d]pyrimidin-2-yl]ethyl}-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-[(1-methylpiperidin-4-yl)methyl]acetamide). RAMX3 is chemically derived from 8-azaquinazolinone-type allosteric modulators and binds to the CXCR3 receptor with a K(d) value of 1.08 nM (specific activity: 80.4 Ci mmol(-1) ). Radioligand displacement assays showed potent negative cooperativity between RAMX3 and chemokine CXCL11, providing a basis for the use of RAMX3 to investigate other potential allosteric modulators. Additionally, the synthesis and characterization of a number of other full and truncated 8-azaquinazoline analogues were used to validate the binding properties of RAMX3. We demonstrate that RAMX3 can be efficiently used to facilitate the discovery and characterization of small molecules as allosteric modulators of the CXCR3 receptor.
ChemMedChem 06/2012; 7(8):1481-9. · 3.15 Impact Factor
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ABSTRACT: The highly constitutively active G-protein coupled receptor US28 of human cytomegalovirus (HCMV) is an interesting pharmacological target because of its implication on viral dissemination, cardiovascular diseases and tumorigenesis. We found that dihydroisoquinolinone and tetrahydroisoquinoline scaffolds may be promising lead structures for novel US28 allosteric inverse agonists. These scaffolds were rapidly synthesized by radical carboamination reactions followed by non-radical transformations. Our novel US28 allosteric modulators provide valuable scaffolds for further ligand optimization and may be helpful chemical tools to investigate molecular mechanisms of US28 constitutive signaling and its role in pathogenesis.
Bioorganic & medicinal chemistry letters 09/2011; 21(18):5446-50. · 2.65 Impact Factor
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Chemistry 08/2011; 17(34):9306-10. · 5.93 Impact Factor
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ABSTRACT: This review summarizes recent advances in the field of aryl radical chemistry. In particular, modern developments of the well-known Meerwein, Pschorr, and Gomberg-Bachmann reactions are presented along with new applications in natural product syntheses. Among the methods for the generation of aryl radicals, tin hydrides play a predominant role, but more and more attractive and promising alternatives are beginning to emerge.
Topics in current chemistry 04/2011; 320:33-59. · 4.29 Impact Factor
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ABSTRACT: A small library of Fmoc-protected 3-arylated tyrosines was created by radical arylation. The new building blocks were successfully applied in the synthesis of two novel neurotensin receptor ligands. Both isomers showed high affinity for the human NTS2 receptor with K(i) values in the nanomolar range. Interestingly, subtype selectivity strongly depends on the configuration of the peptide in position 11. Isomer (11R)-3 displayed an excellent preference for NTS2 compared to NTS1.
Organic & Biomolecular Chemistry 04/2011; 9(10):3746-52. · 3.70 Impact Factor
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Chemistry 03/2011; 17(15):4104-8. · 5.93 Impact Factor
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Angewandte Chemie International Edition 11/2010; 49(50):9769-72. · 13.45 Impact Factor
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ABSTRACT: Radical arylations of para-substituted phenols and phenyl ethers proceeded with good regioselectivity at the ortho position with respect to the hydroxy or alkoxy group. The reactions were conducted with arenediazonium salts as the aryl radical source, titanium(III) chloride as the reductant, and diluted hydrochloric acid as the solvent. Substituted biaryls were obtained from hydroxy- and alkoxy-substituted benzylamines, phenethylamines, and aromatic amino acids. The methodology described offers a fast, efficient, and cost-effective new access to diversely functionalized biphenyl alcohols and ethers. Free phenolic hydroxy groups, aromatic and aliphatic amines, as well as amino acid substructures, are well tolerated. Two examples for the applicability of the methodology are the partial synthesis of a beta-secretase inhibitor and the synthesis of a calcium-channel modulator.
Chemistry 02/2010; 16(8):2547-56. · 5.93 Impact Factor
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Markus R Heinrich
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ABSTRACT: This minireview is aimed at giving an overview of recent advances in olefin functionalisation reactions involving aryl radicals generated from arenediazonium salts. Based on the well-known Meerwein arylation, in which an aryl and a halogen substituent are coupled to an olefinic substrate, new reaction types have been developed that allow the introduction of a broad spectrum of other atoms and functional groups at the place of the original halogen atom and that are applicable to an extended range of olefinic substrates.
Chemistry 01/2009; 15(4):820-33. · 5.93 Impact Factor
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Annalen der Chemie und Pharmacie 05/2008; 2008(18):3179 - 3189. · 3.10 Impact Factor
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Angewandte Chemie International Edition 02/2008; 47(47):9130-3. · 13.45 Impact Factor
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ABSTRACT: Allylation and vinylation of aryl radicals generated from aryl diazonium salts provides rapid and efficient access to chlorinated and brominated derivatives of styrene and allylbenzene. Allyl chlorides were found to be better substrates than bromides due to decreased halogen transfer. Donor- and acceptor-substituted diazonium salts are well tolerated. The products represent important precursors for numerous further transformations.
The Journal of Organic Chemistry 01/2008; 72(25):9609-16. · 4.45 Impact Factor
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ABSTRACT: Highly reactive aryl radicals can selectively be reacted with a broad variety of activated and nonactivated olefinic substrates in the presence of nitroxyl radicals. Direct recombination of the aryl radical and the nitroxide as well as telomerization of the olefin is successfully suppressed by the reaction conditions.
Organic Letters 10/2007; 9(19):3833-5. · 5.86 Impact Factor
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ABSTRACT: Procedures for the carbodiazenylation of nonactivated olefins with a wide range of aryldiazonium salts have been developed. The azo compounds obtained can serve as valuable precursors for beta-arylamines (carboamination products), beta-amino acids, ketones, and various heterocyclic structures.
The Journal of Organic Chemistry 02/2007; 72(2):476-84. · 4.45 Impact Factor
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Annalen der Chemie und Pharmacie 08/2006; 2006(19):4331 - 4334. · 3.10 Impact Factor
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ABSTRACT: [Structure: see text] The reduction of aryl diazonium salts in the presence of nonactivated olefins provides rapid entry to carbodiazenylation products. The regioselective functionalization of double bonds is achieved in a one-pot process starting from aniline derivatives. Carboamination of olefins is possible via a two-step carbodiazenylation-hydrogenation sequence in which one aniline equivalent is recovered.
Organic Letters 08/2006; 8(15):3323-5. · 5.86 Impact Factor
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ABSTRACT: Aziridine N-carbonyl radicals, generated by irradiating the corresponding S-oxalyl xanthates, undergo ring opening to give 2-isocyanato radicals, which can be trapped by an external olefin.
Chemical Communications 01/2006; · 6.17 Impact Factor
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ABSTRACT: Gamma-carbonyl vinyl boronates can be prepared by a visible light induced radical chain addition of an S-acyl dithiocarbonate (xanthate) to the pinacol ester of vinyl boronic acid, followed by treatment with base.
Chemical Communications 07/2005; · 6.17 Impact Factor
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ABSTRACT: [reaction: see text] Cyclopropylacyl radicals derived from S-cyclopropylacyl xanthates (dithiocarbonates) undergo intermolecular additions to olefins without loss of CO or ring opening. In the presence of a phenyl ring on carbon C-1 of the cyclopropane ring, loss can be made to occur in the absence of an olefinic trap. The adducts from the cyclopropylacyl radical additions are easily converted into enones by base-induced beta-elimination of the xanthate group.
Organic Letters 01/2005; 6(26):4969-72. · 5.86 Impact Factor
