- Multicomponent mapping of boron chemotypes furnishes selective enzyme inhibitors
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Heteroatom-rich organoboron compounds have attracted attention as modulators of enzyme function. Driven by the unmet need to develop chemoselective access to boron chemotypes, we report herein the synthesis of α-and β-aminocyano(MIDA)boronates from borylated carbonyl compounds. Activity-based protein profiling of the resulting β-aminoboronic acids furnishes selective and cell-active inhibitors of the (ox)lipid-metabolizing enzyme α/β-hydrolase domain 3 (ABHD3). The most potent compound displays nanomolar in vitro and in situ IC50 values and fully inhibits ABHD3 activity in human cells with no detectable cross-reactivity against other serine hydrolases. These findings demonstrate that synthetic methods that enhance the heteroatom diversity of boron-containing molecules within a limited set of scaffolds accelerate the discovery of chemical probes of human enzymes.
- Tan, Joanne,Iii, Armand B. Cognetta,Diaz, Diego B.,Lum, Kenneth M.,Adachi, Shinya,Kundu, Soumajit,Cravatt, Benjamin F.,Yudin, Andrei K.
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Read Online
- Building Block Approach for the Synthesis of Sulfoximines
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A cross-coupling strategy for the preparation of novel sulfoximines via preformed sulfoximidoyl-containing building blocks has been developed. It allows obtaining a wide range of products in good yields under mild reaction conditions, and it can be applied in late-stage functionalizations, as demonstrated by the synthesis of a sulfoximine-based analogue of a recently reported potent valosine-containing protein inhibitor.
- Steinkamp, Anne-Dorothee,Wiezorek, Stefan,Brosge, Felix,Bolm, Carsten
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Read Online
- NOVEL BORONIC ESTERS AND METHODS FOR MAKING THE SAME
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There is provide herein a compound of Formula (1): wherein R1, R2, R3, R4, and R5 are each independently H or an organic group.
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Paragraph 0133
(2020/12/20)
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- A Mild Method for Making MIDA Boronates
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We disclose that a predried form of methyliminodiacetic acid (MIDA), MIDA anhydride, acts as both a source of the MIDA ligand and an in situ desiccant to enable a mild and simple MIDA boronate synthesis procedure. This method expands the range of sensitive boronic acids that can be converted into their MIDA boronate counterparts. Further utilizing unique properties of MIDA boronates, we have developed a MIDA Boronate Maker Kit which enables the direct preparation and purification of MIDA boronates from boronic acids using only heating and centrifuge equipment that is widely available in laboratories that do not specialize in organic synthesis.
- Kelly, Aidan M.,Chen, Peng-Jui,Klubnick, Jenna,Blair, Daniel J.,Burke, Martin D.
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supporting information
p. 9408 - 9414
(2020/09/15)
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- Fe-Catalyzed Reductive Couplings of Terminal (Hetero)Aryl Alkenes and Alkyl Halides under Aqueous Micellar Conditions
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The combination of a vinyl-substituted aromatic or heteroaromatic and an alkyl bromide or iodide leads, in the presence of Zn and a catalytic amount of an Fe(II) salt, to a net reductive coupling. The new C-C bond is regiospecifically formed at rt at the β-site of the alkene. The coupling only occurs in an aqueous micellar medium, where a radical process is likely, supported by several control experiments. A mechanism based on these data is proposed.
- Pang, Haobo,Wang, Ye,Gallou, Fabrice,Lipshutz, Bruce H.
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supporting information
p. 17117 - 17124
(2019/11/03)
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- N-Arylated Sulfoximines as Cross-Coupling Building Blocks
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The application of borylated N-aryl sulfoximines as newly designed synthetic building blocks in Suzuki-type cross coupling reactions offers rapid access to a wide range of N-biaryl derivatives with potential relevance for medicinal chemistry and crop protection in good to excellent yields (up to 98%). (Figure presented.).
- Bachon, Anne-Katrin,Steinkamp, Anne-Dorothee,Bolm, Carsten
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supporting information
p. 1088 - 1093
(2018/01/27)
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- A General Protocol for the Polycondensation of Thienyl N-Methyliminodiacetic Acid Boronate Esters to Form High Molecular Weight Copolymers
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Thienyl di-N-methyliminodiacetic acid (MIDA) boronate esters are readily synthesized by electrophilic C-H borylation producing bench stable crystalline solids in good yield and excellent purity. Optimal conditions for the slow release of the boronic acid using KOH as the base in biphasic THF/water mixtures enables the thienyl MIDA boronate esters to be extremely effective homo-bifunctionalized (AA-type) monomers in Suzuki-Miyaura copolymerizations with dibromo-heteroarenes (BB-type monomers). A single polymerization protocol is applicable for the formation of five alternating thienyl copolymers that are (or are close analogues of) state of the art materials used in organic electronics. The five polymers were produced in excellent yields and with high molecular weights comparable to those produced using Stille copolymerization protocols. Therefore, thienyl di-MIDA boronate esters represent bench stable and low toxicity alternatives to highly toxic di-trimethylstannyl AA-type monomers that are currently ubiquitous in the synthesis of these important alternating copolymers.
- Carrillo, Josue Ayuso,Turner, Michael L.,Ingleson, Michael J.
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supporting information
p. 13361 - 13368
(2016/10/22)
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- A general method for interconversion of boronic acid protecting groups: Trifluoroborates as common intermediates
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We have developed a general protocol for the interconversion of diverse protected boronic acids, via intermediate organotrifluoroborates. N-Methyliminodiacetyl boronates, which have been hitherto resistant to direct conversion to trifluoroborates, have been shown to undergo fluorolysis at elevated temperatures. Subsequent solvolysis of organotrifluoroborates in the presence of trimethylsilyl chloride and a wide range of bis-nucleophiles enables the generation of a variety of protected boronic acids.
- Churches, Quentin I.,Hooper, Joel F.,Hutton, Craig A.
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p. 5428 - 5435
(2015/06/16)
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- Boroalkyl group migration provides a versatile entry into α-aminoboronic acid derivatives
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A reaction exemplifying migration of boron-substituted carbon is described. We show that α-boroalkyl groups of transient boroalkyl acyl azide intermediates readily migrate from carbon to nitrogen. This process allows access to a new class of stable molecules, α-boryl isocyanates, from α-borylcarboxylic acid precursors. The methodology facilitates synthesis of a wide range of α-aminoboronic acid derivatives, including α,α-disubstituted analogues.
- He, Zhi,Zajdlik, Adam,St. Denis, Jeffrey D.,Assem, Naila,Yudin, Andrei K.
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supporting information; experimental part
p. 9926 - 9929
(2012/08/07)
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- General method for synthesis of 2-heterocyclic N-methyliminodiacetic acid boronates
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A wide range of 2-pyridyl and other difficult-to-access heterocyclic N-methyliminodiacetic acid boronates can be readily prepared from the corresponding bromides via a new method involving direct transligation of 2-heterocyclic trialkoxyborate salts with N-methyliminodiacetic acid (MIDA) at elevated temperatures.
- Dick, Graham R.,Knapp, David M.,Gillis, Eric P.,Burke, Martin D.
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supporting information; experimental part
p. 2314 - 2317
(2010/08/04)
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- Synthesis of dianionic and trianionic chiral, chelating ligands based on amino acids
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The synthesis of two new families of amino acid-containing chiral ligands, based on methyliminodiacetic acid and nitrilotriacetic acid cores, has been accomplished using a simple protection, solution-phase amide coupling, and deprotection strategy. The amino acids glycine, leucine, aspartic acid, and phenylalanine were used to demonstrate the versatility of the synthetic route, and that no epimerization occurs. The tridentate ligands bear C3 symmetry, whereas the bidentate ligands have C1 symmetry. CSIRO 2008.
- Schultz, Madeleine,Kulis, Jakov,Murison, Julie,Andrews, Genevieve W.
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p. 297 - 302
(2008/09/19)
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- Polypodal chelants for metallopharmaceuticals
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Polypodal chelants are disclosed, as well as chelates of the chelants with metal ions to form radiopharmaceutical and radioactive, MRI and X-ray or CT imaging compounds and compositions. Therapeutic and imaging methods of use are also disclosed.
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- Syntheses of (N → B)phenyl[N-alkylaminodiacetate-O,O′,N]boranes
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The syntheses of (N → B)phenyl[N-alkylaminodiacetate-O,O′,N]boranes (2 to 6) and their corresponding N-alkylaminodiacetic acids (7 to 10) are reported. All compounds (except 6) were characterized by 1H, 11B (for boron heterocycles), 13C NMR, infrared spectroscopy and mass spectrometry. The 1H NMR spectrum of compound 3 shows that it is a chiral molecule, its structure was determined by homonuclear decoupling experiments, 1H NMR and HETCOR. The study of the intramolecular N → B coordination by dynamic NMR afforded a ΔG? value of 98.4 kJ mol-1 for compound 3. Copyright
- Mancilla, Teresa,Carrillo, Lourdes,De La Paz Reducindo
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p. 3777 - 3785
(2008/10/09)
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- Mass Spectra of Butyl Esters and N-Trifluoroacetyl Butyl Esters of Some Iminodicarboxylic Acids upon Electron Impact
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Mass spectra (electron impact at 20 eV) of butyl esters and N-trifluoroacetyl (TFA) butyl esters of some iminodicarboxylic acids (IDCAs) were determined by gas chromatography-mass spectrometry.The IDCAs included iminodiacetic acid (1), 2-(carboxymethylamino)propionic acid (2), 3-(carboxymethylamino)propionic acid (3), 2,2'-iminodipropionic acid (4), 2,3'-iminodipropionic acid (5), 3,3'-iminodipropionic acid (6), N-methylaminodiacetic acid (7), and nitrilotriacetic acid (8).The mass spectra of the butyl ester derivatives are simple, exhibiting the corresponding molecular (M+) ions with the exception of 5.The α,α'-IDCAs (1, 2, 4, 7, and 8) are characterized by M+, M -101 (COOC4H9) (base peak), and M - 157 (COOC4H9 + C4H8) ions.The β,β'-IDCA (6) is characterized by a more complex spectrum with M+, M - 73 (OC4H9), M - 115 (CH2COOC4H9) (base peak), M - 129 (OC4H9 + C4H9), and M - 171 (CH2COOC4H9 + C4H9) ions.The α,β'-IDCAs (3 and 5) in general show spectra in which both ions characteristic of α,α'- and β,β'-IDCAs are observed.The addition of TFA to the imino nitrogens of 1 - 6 increases complexity of the resulting spectra.In these instances, although M+ ions are usually present, neither M - 101 nor 115 ions are base peaks.The fragmentation pathways of these two volatile derivatives of the IDCAs upon electron impact are discussed.
- Kawashiro, Katsuhiro,Morimoto, Shiro,Yoshida, Hideyuki
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p. 1097 - 1103
(2007/10/02)
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