13051-32-6Relevant articles and documents
Lewis base-catalyzed Michael reactions between trimethylsilyl enolate and α,β-unsaturated carbonyl compounds
Nakagawa, Takashi,Fujisawa, Hidehiko,Nagata, Yuzo,Mukaiyama, Teruaki
, p. 236 - 246 (2005)
Michael reactions between trimethylsilyl enolates and α,β- unsaturated carbonyl compounds by using a Lewis base catalyst such as lithium benzamide 4 or lithium succinimide 5 in DMF proceeded smoothly to afford the corresponding Michael-adducts in good to high yields (Tables 1-3). In order to extend the scope, Michael reactions catalyzed by lithium acetate (AcOLi), a weak and readily available Lewis base, were studied in detail. AcOLi behaved as an effective Lewis base catalyst in Michael reactions between trimethylsilyl enolates and α,β-unsaturated carbonyl compounds at 0 °C or at room temperature (Tables 4-6). Hindered α,β-unsaturated ketones behaved as excellent Michael-acceptors in the above reaction at room temperature (Table 5). This catalytic Michael reaction also proceeds smoothly in the presence of other lithium carboxylates that are easily prepared in situ by treating carboxylic acids with lithium carbonate (LE2CO3) (Scheme 2). This is the first example of Lewis base-catalyzed Michael reactions between α,β-unsaturated carbonyl compounds and trimethylsilyl enolates.
Design, Synthesis, and Biological Evaluation of IRAK4-Targeting PROTACs
Chen, Yun,Ning, Yi,Bai, Gang,Tong, Linjiang,Zhang, Tao,Zhou, Jinpei,Zhang, Huibin,Xie, Hua,Ding, Jian,Duan, Wenhu
, p. 82 - 87 (2021)
Interleukin-1 receptor associated kinase 4 (IRAK4) is a promising therapeutic target for diffuse large B-cell lymphoma driven by MYD88 L265P mutant, acting both as a kinase and a scaffolding protein for downstream signaling molecules. While previous efforts to modulate IRAK4 activity with kinase inhibitors alone displayed moderate efficacy, protein degradation may offer a solution to blocking both IRAK4 kinase activity and scaffolding capabilities. To this end, the potent IRAK4 degrader 9 was discovered, and it effectively inhibited the activation of downstream NF-κB signaling and outperformed the parent compound 1. In addition, compound 9 displayed a substantial advantage in reduction of the viability of OCI-LY10 and TMD8 cells over the parent compound 1. These results underline the potential that eliminating both the kinase and scaffolding functions of IRAK4 may result in superior and broader efficacy than inhibiting the kinase activity alone.
Chain propagation determines the chemo- And regioselectivity of alkyl radical additions to C-O: Vs. C-C double bonds
Paulisch, Tiffany O.,Strieth-Kalthoff, Felix,Henkel, Christian,Pitzer, Lena,Guldi, Dirk M.,Glorius, Frank
, p. 731 - 736 (2020/02/03)
Investigations into the selectivity of intermolecular alkyl radical additions to C-O- vs. C-C-double bonds in α,β-unsaturated carbonyl compounds are described. Therefore, a photoredox-initiated radical chain reaction is explored, where the activation of the carbonyl-group through an in situ generated Lewis acid-originating from the substrate-enables the formation of either C-O or the C-C-addition products. α,β-Unsaturated aldehydes form selectively 1,2-, while esters and ketones form the corresponding 1,4-addition products exclusively. Computational studies lead to reason that this chemo- and regioselectivity is determined by the consecutive step, i.e. an electron transfer, after reversible radical addition, which eventually propagates the radical chain.
CYCLIN-DEPENDENT KINASE 2 BIOMARKERS AND USES THEREOF
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Page/Page column 120, (2020/08/28)
Biomarkers are provided that are predictive and/or indicative of a subject's responsiveness to a cyclin-dependent kinase 2 (CDK2) inhibitor. The biomarkers, compositions, and methods described herein are useful in selecting appropriate treatment modalities for a subject having, suspected of having, or at risk of developing a disease or disorder associated with CDK2 and for monitoring treatment.
