1202794-01-1Relevant articles and documents
Gram-Negative Antibiotic Active through Inhibition of an Essential Riboswitch
Geddes, Emily J.,Hergenrother, Paul J.,Lau, Gee W.,Lee, Hyang Yeon,Motika, Stephen E.,Ulrich, Rebecca J.
, p. 10856 - 10862 (2020)
Multidrug-resistant Gram-negative (GN) infections for which there are few available treatment options are increasingly common. The development of new antibiotics for these pathogens is challenging because of the inability of most small molecules to accumulate inside GN bacteria. Using recently developed predictive guidelines for compound accumulation in Escherichia coli, we have converted the antibiotic Ribocil C, which targets the flavin mononucleotide (FMN) riboswitch, from a compound lacking whole-cell activity against wild-type GN pathogens into a compound that accumulates to a high level in E. coli, is effective against Gram-negative clinical isolates, and has efficacy in mouse models of GN infections. This compound allows for the first assessment of the translational potential of FMN riboswitch binders against wild-type Gram-negative bacteria.
Cyclic (Alkyl)(amino)carbene Ligands Enable Cu-Catalyzed Markovnikov Protoboration and Protosilylation of Terminal Alkynes: A Versatile Portal to Functionalized Alkenes**
Bertrand, Guy,Engle, Keary M.,Gao, Yang,Grotjahn, Douglas B.,Jazzar, Rodolphe,Junor, Glen P.,Kang, Taeho,Kendrick, Aaron,Yazdani, Sima
supporting information, p. 19871 - 19878 (2021/08/13)
Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or rea
Suzuki coupling of aroyl-MIDA boronate esters – A preliminary report on scope and limitations
Lai, Samson,Lin, Wen Xuan,Perrin, David M.,Takaesu, Noah
supporting information, (2021/05/31)
Recent methodological reports for synthesizing acyl-MIDA boronate esters compel an investigation of their potential use as substrates in a standard Suzuki-Miyaura cross-coupling reaction. Here we report the production of benzophenones by C[sbnd]C cross coupling between a benzoyl-MIDA boronate ester and a multitude of aryl bromide substrates in adequate yields following optimization under ambient conditions outside of a glove box. Under these standard conditions, none of several acyl-MIDA boronate esters (in an alkyl series) serves as a competent coupling partner. The substrate scope is also limited by the finding that the corresponding trifluoroborates of both acyl- and aroyltrifluroborates are not suitable substrates. For reasons of availability and synthetic difficulty in procuring other aroyl-MIDA boronates, this preliminary study examines the reactivity of benzoyl-MIDA boronate with several aryl bromide substrates.
DNA-PK inhibitor
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Paragraph 0191-0194, (2021/03/31)
The invention belongs to the technical field of medicines, and particularly relates to a class of compounds capable of being used as an inhibitor of DNA-dependent protein kinase (DNA-PK), a pharmaceutically acceptable salt, a deuterated substance and a stereoisomer thereof, a pharmaceutical composition and a preparation containing the compound, the pharmaceutically acceptable salt, the deuteratedsubstance and the stereoisomer thereof, and uses of the compound, the pharmaceutically acceptable salt, the deuterated compound and the stereoisomer thereof.
Heterocyclic kinase inhibitor
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Paragraph 0206-0209, (2021/03/31)
The invention belongs to the technical field of medicines, and particularly relates to a heterocyclic DNA-PK kinase inhibitor compound shown as a general formula (I), a pharmaceutically acceptable salt and an isomer thereof, a pharmaceutical composition and preparation containing the compound, the pharmaceutically acceptable salt and the isomer thereof, a method for preparing the compound, the pharmaceutically acceptable salt and the isomer thereof, and application of the compound, the pharmaceutically acceptable salt and the isomer thereof.
Combining Copper-Catalyzed Hydroboration with Palladium-Catalyzed Suzuki Coupling for the One-pot Synthesis of Arylallylamines under Micellar Conditions
Horn, Pedro A.,Braun, Roger K.,Isoppo, Victória G.,Costa, Jessie S. da,Lüdtke, Diogo S.,Moro, Angélica V.
supporting information, p. 2322 - 2328 (2017/07/07)
Herein we report the one-pot dual-metal catalytic synthesis of arylallylamines, by combination of a Cu-catalyzed hydroboration with a Pd-catalyzed Suzuki arylation, using a broad range of aryl halides. Importantly, the reaction sequence was entirely performed in water, in the presence of small amounts of SPGS-550M, without the need of solvent switch or addition of organic co-solvents, rendering it operationally simple and environmentally benign. The usefulness of this methodology was highlighted in a short synthesis of the pharmaceutically important compound naftifine. (Figure presented.).
Copper-catalyzed hydroboration of propargyl-functionalized alkynes in water
Da Costa, Jessie S.,Braun, Roger K.,Horn, Pedro A.,Lüdtke, Diogo S.,Moro, Angélica V.
, p. 59935 - 59938 (2016/07/11)
The Cu-catalyzed hydroboration of alkynes in operationally simple and environmentally friendly conditions is reported. The reactions are performed in water, at room temperature, under micellar catalysis. Conditions to form the α or β borylated products se
A broadly applicable NHC-Cu-catalyzed approach for efficient, site-, and enantioselective coupling of readily accessible (pinacolato)alkenylboron compounds to allylic phosphates and applications to natural product synthesis
Gao, Fang,Carr, James L.,Hoveyda, Amir H.
, p. 2149 - 2161 (2014/03/21)
A set of protocols for catalytic enantioselective allylic substitution (EAS) reactions that allow for additions of alkenyl units to readily accessible allylic electrophiles is disclosed. Transformations afford 1,4-dienes that contain a tertiary carbon stereogenic site and are promoted by 1.0-5.0 mol % of a copper complex of an N-heterocyclic carbene (NHC). Aryl- as well as alkyl-substituted electrophiles bearing a di- or trisubstituted alkene may be employed. Reactions can involve a variety of robust alkenyl-(pinacolatoboron) [alkenyl-B(pin)] compounds that can be either purchased or prepared by various efficient, site-, and/or stereoselective catalytic reactions, such as cross-metathesis or proto-boryl additions to terminal alkynes. Vinyl-, E-, or Z-disubstituted alkenyl-, 1,1-disubstituted alkenyl-, acyclic, or heterocyclic trisubstituted alkenyl groups may be added in up to >98% yield, >98:2 SN2′:SN2, and 99:1 enantiomeric ratio (er). NHC-Cu-catalyzed EAS with alkenyl-B(pin) reagents containing a conjugated carboxylic ester or aldehyde group proceed to provide the desired 1,4-diene products in good yield and with high enantioselectivity despite the presence of a sensitive stereogenic tertiary carbon center that could be considered prone to epimerization. In most instances, the alternative approach of utilizing an alkenylmetal reagent (e.g., an Al-based species) represents an incompatible option. The utility of the approach is illustrated through applications to enantioselective synthesis of natural products such as santolina alcohol, semburin, nyasol, heliespirone A, and heliannuol E.
Formal regiocontrolled hydroboration of unbiased internal alkynes via borylation/allylic alkylation of terminal alkynes
Moure, Abraham L.,Mauleon, Pablo,Arrayas, Ramon Gomez,Carretero, Juan Carlos
supporting information, p. 2054 - 2057 (2013/06/04)
In accessing trisubstituted vinyl boronates from terminal alkynes, a propargyl directing (2-pyridyl)sulfonyl group allows terminal alkynes to undergo Cu-catalyzed B2(pin)2-borylation and subsequent Cu-catalyzed allylic alkylation wit
Metal free catalytic hydroboration of multiple bonds in methanol using N-heterocyclic carbenes under open atmosphere
Wen, Kun,Chen, Jinbo,Gao, Feng,Bhadury, Pinaki S.,Fan, Erkang,Sun, Zhihua
, p. 6350 - 6356 (2013/09/23)
An easy to operate method of catalytic hydroboration of unsaturated compounds has been developed with wide substrate scope. Reactions of various aldimines, ketimines, α,β-unsaturated carbonyl compounds, and alkynes were successfully executed with bis(pinacolato)diboron and N-heterocyclic carbenes in methanol without requiring a transition metal or inert atmosphere.
