120591-36-8Relevant academic research and scientific papers
Hydrogenative Cyclopropanation and Hydrogenative Metathesis
Peil, Sebastian,Guthertz, Alexandre,Biberger, Tobias,Fürstner, Alois
, p. 8851 - 8856 (2019)
The unusual geminal hydrogenation of a propargyl alcohol derivative with [CpXRuCl] as the catalyst entails formation of pianostool ruthenium carbenes in the first place; these reactive intermediates can be intercepted with tethered alkenes to give either cyclopropanes or cyclic olefins as the result of a formal metathesis event. The course of the reaction is critically dependent on the substitution pattern of the alkene trap.
Cationic Au(I)- and Pt(II)-catalyzed silylation of alcohols using allylsilanes
Shibata, Takanori,Kanda, Kazumasa,Ueno, Yasunori,Fujiwara, Ryo
, p. 1146 - 1147 (2006)
The silylation of alcohols using allylsilanes was catalyzed by cationic Au(I) and Pt(II) species, which were prepared in situ from the metal chlorides ([AuCl(PPh3)], PtCl2) and a silver salt. TBS-, TES-, and TIPS-protections of vario
Unlocking a Diazirine Long-Lived Nuclear Singlet State via Photochemistry: NMR Detection and Lifetime of an Unstabilized Diazo-Compound
Procacci, Barbara,Roy, Soumya S.,Norcott, Philip,Turner, Norman,Duckett, Simon B.
, p. 16855 - 16864 (2018)
Diazirines are important for photoaffinity labeling, and their photoisomerization is relatively well-known. This work shows how hyperpolarized NMR spectroscopy can be used to characterize an unstable diazo-compound formed via photoisomerization of a 15N2-labeled silyl-ether-substituted diazirine. This diazirine is prepared in a nuclear spin singlet state via catalytic transfer of spin order from para-hydrogen. The active hyperpolarization catalyst is characterized to provide insight into the mechanism. The photochemical isomerization of the diazirine into the diazo-analogue allows the NMR invisible nuclear singlet state of the parent compound to be probed. The identity of the diazo-species is confirmed by trapping with N-phenyl maleimide via a cycloaddition reaction to afford bicyclic pyrazolines that also show singlet state character. The presence of singlet states in the diazirine and the diazo-compound is validated by comparison of experimental nutation behavior with theoretical simulation. The magnetic state lifetime of the diazo-compound is determined as 12 ± 1 s in CD3OD solution at room temperature, whereas its chemical lifetime is measured as 100 ± 5 s by related hyperpolarized NMR studies. Indirect evidence for the generation of the photoproduct para-N2 is presented.
Incorporation of β-Silicon-β3-Amino Acids in the Antimicrobial Peptide Alamethicin Provides a 20-Fold Increase in Membrane Permeabilization
Madsen, Julie L. H.,Hj?rringgaard, Claudia U.,Vad, Brian S.,Otzen, Daniel,Skrydstrup, Troels
, p. 8358 - 8367 (2016)
Incorporation of silicon-containing amino acids in peptides is known to endow the peptide with desirable properties such as improved proteolytic stability and increased lipophilicity. In the presented study, we demonstrate that incorporation of β-silicon-β3-amino acids into the antimicrobial peptide alamethicin provides the peptide with improved membrane permeabilizing properties. A robust synthetic procedure for the construction of β-silicon-β3-amino acids was developed and the amino acid analogues were incorporated into alamethicin at different positions of the hydrophobic face of the amphipathic helix by using SPPS. The incorporation was shown to provide up to 20-fold increase in calcein release as compared with wild-type alamethicin.
Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing an Intermediate for Squalestatin Synthesis
Almohseni, Hasanain A. A.,Arif, Tanzeel,Fegheh-Hassanpour, Younes,Hodgson, David M.
, p. 4231 - 4238 (2019)
Studies on both the propensity for intramolecular cycloaddition between diazo and alkene functionality, and the tolerance of α-substituted α-diazoesters towards ozone in the presence of an alkene, led to chemoselective alkene ozonolysis of an ?-unsaturated-α-diazoester to give a key racemic diazoketone for the synthesis of 6,7-dideoxysqualestatin H5.
Hydrogenative metathesis of enynes via piano-stool ruthenium carbene complexes formed by alkyne gem-hydrogenation
Peil, Sebastian,Bistoni, Giovanni,Goddard, Richard,Fürstner, Alois
supporting information, p. 18541 - 18553 (2020/11/17)
The only recently discovered gem-hydrogenation of internal alkynes is a fundamentally new transformation, in which both H atoms of dihydrogen are transferred to the same C atom of a triple bond while the other position transforms into a discrete metal carbene complex. [Cp?RuCl]4 is presently the catalyst of choice: the resulting piano-stool ruthenium carbenes can engage a tethered alkene into either cyclopropanation or metathesis, and a prototypical example of such a reactive intermediate with an olefin ligated to the ruthenium center has been isolated and characterized by X-ray diffraction. It is the substitution pattern of the olefin that determines whether metathesis or cyclopropanation takes place: a systematic survey using alkenes of largely different character in combination with a computational study of the mechanism at the local coupled cluster level of theory allowed the preparative results to be sorted and an intuitive model with predictive power to be proposed. This model links the course of the reaction to the polarization of the double bond as well as to the stability of the secondary carbene complex formed, if metathesis were to take place. The first application of "hydrogenative metathesis"to the total synthesis of sinularones E and F concurred with this interpretation and allowed the proposed structure of these marine natural products to be confirmed. During this synthesis, it was found that gem-hydrogenation also provides opportunities for C-H functionalization. Moreover, silylated alkynes are shown to participate well in hydrogenative metathesis, which opens a new entry into valuable allylsilane building blocks. Crystallographic evidence suggests that the polarized [Ru-Cl] bond of the catalyst interacts with the neighboring R3Si group. Since attractive interligand Cl/R3Si contacts had already previously been invoked to explain the outcome of various ruthenium-catalyzed reactions, including trans-hydrosilylation, the experimental confirmation provided herein has implications beyond the present case.
BENZIMIDAZOLONE DERIVED INHIBITORS OF BCL6
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Paragraph 00390, (2018/12/13)
The present invention relates to compounds of Formula I that function as inhibitors of BCL6 (B-cell lymphoma 6) activity: wherein X1, X2, R1, R2 and R3 are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which BCL6 activity is implicated.
Deoxyalkoxyamination of Alcohols for the Synthesis of N-Alkoxy-N-alkylbenzenesulfonamides
Sun, Qi-An,Lu, Ze-Hai,Pu, Xiao-Qiu,Hu, Hui-Lian,Zhang, Jia-heng,Yang, Xian-Jin
supporting information, p. 3920 - 3927 (2018/07/31)
A novel protocol for the deoxyalkoxyamination of alcohols has been developed, using N-alkoxybenzenesulfonimide (NOSI) as both a sulfonyl transfer reagent and an alkoxyamine source, accessing a diverse range of N-alkoxy-N-alkylbenzenesulfonamides with excellent isolated yields. This method is characterized by metal-free reaction, scalability, and waste-balance. Chiral substrates are converted with excellent levels of stereochemical inversion. NOSI could be generated in situ during the reaction as a stable reagent if a three-component one-pot reaction was designed. Exploiting this approach to run intramolecular reactions offered various N-protected isoxazolidines. In addition, valuable O-alkyl hydroxylamines (or isoxazolidines) were obtained through a neutral strategy of desulfonylation of the products.
Stereoselective Synthesis of a Highly Oxygenated δ-Lactone Related to the Core Structure of (-)-Enterocin
Wegmann, Marcus,Bach, Thorsten
supporting information, p. 209 - 217 (2016/12/24)
The title compound was prepared in a concise route starting from an appropriately protected (S)-glyceraldehyde. A highly diastereoselective (d.r. >95:5) Mukaiyama aldol reaction of an acetoacetate-derived silyl enol ether served as the initial step of the synthetic sequence. It was found that protection of the glyceraldehyde as a butane-2,3-dione acetal is required to achieve the desired diastereoselectivity. Upon lactonization, a Tsuji-Trost allylation and a subsequent one-pot reaction cascade including an ozonolysis and an α-hydroxylation gave diastereoselective access to the desired α-hydroxy-β-oxo-δ-lactone. Alternative synthetic approaches are discussed and proof for the configuration of the product is presented.
ISOXAZOLE DERIVATIVE AS MUTATED ISOCITRATE DEHYDROGENASE 1 INHIBITOR
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Paragraph 0256; 0257, (2018/02/06)
It has been found that a compound of the general formula (I) having an isoxazole skeleton has excellent inhibitory activity against mutant IDH1 protein and inhibits the production of 2-HG by this protein, while the compound is also capable of effectively inhibiting the growth of various tumors expressing the protein. In the formula, R1, R2, R3, Y, and Z are as defined in claim 1.
