76911-01-8Relevant articles and documents
Polycyclic Cyclopropanes from Reactions of Alkene-Containing Fischer Carbene Complexes and Alkynes: A Formal Synthesis of (+/-)-Carabrone
Hoye, Thomas R.,Vyvyan, James R.
, p. 4184 - 4195 (1995)
The polycyclic cyclopropanation reaction of several alkene-containing Fischer carbene complexes with various alkyne partners to provide bicyclo enol ethers and ketones was examined.A number of features were probed, including the role of carbene don
Bifunctional Fluoroalcohol Catalysts Enabled Sustainable Synthesis of Poly(amino acid)s?
He, Wenjing,Tao, Youhua
supporting information, p. 2119 - 2124 (2021/06/16)
A series of novel bifunctional single-molecule hydrogen-bonding organocatalysts based on fluorinated tertiary alcohol were synthesized to mediate the metal-free polymerization of α-amino acid N-carboxyanhydride (NCA) monomer. Through the screening of catalysts, the polymerization catalyzed by the preferred bifunctional fluoroalcohol catalyst proceeded in a fast and controlled manner, affording high molecular weight polypeptide up to 35.2 × 104 Da with relatively narrow molecular weight distribution (? 1.20). A phenomenon of self-accelerating effect of polymerization induced by α-helical structure of polypeptides was observed, and a possible polymerization pathway has been discussed.
Design and Synthesis of Oleanolic Acid Trimers to Enhance Inhibition of Influenza Virus Entry
Huang, Boxuan,Li, Weijia,Mu, Yu,Shao, Liang,Su, Yangqing,Sun, Mengsi,Xu, Huan,Yang, Fan,Yu, Fei,Zhang, Jihong,Zhang, Yuan
, p. 1759 - 1765 (2021/11/18)
Influenza is a major threat to millions of people worldwide. Entry inhibitors are of particular interest for the development of novel therapeutic strategies for influenza. We have previously discovered oleanolic acid (OA) to be a mild influenza hemagglutinin (HA) inhibitor. In this work, inspired by the 3D structure of HA as a homotrimeric receptor, we designed and synthesized 15 OA trimers with different linkers and central region via the copper-catalyzed azide-alkyne cycloaddition reaction. All of the OA trimers were evaluated for their antiviral activities in vitro, and 12c, 12e, 13c, and 13d were observed to exhibit robust potency (IC50 in the submicromolar range) against influenza A/WSN/33 (H1N1) virus that was stronger than that observed with oseltamivir. In addition, these compounds also displayed strong biological activity against A/Hong Kong/4801/2014 and B/Sichuan/531/2018 (BV). The results of hemagglutination inhibition assays and surface plasmon resonance binding assays suggest that these OA trimers may interrupt the interaction between the HA protein of influenza virus and the host cell sialic acid receptor, thus blocking viral entry. These findings highlight the utility of multivalent OA conjugates to enhance the ligand-target interactions in anti-influenza virus drug design and are also helpful for studying antiviral drugs derived from natural products.
Iridium-Catalyzed Hydrochlorination and Hydrobromination of Alkynes by Shuttle Catalysis
Yu, Peng,Bismuto, Alessandro,Morandi, Bill
supporting information, p. 2904 - 2910 (2020/01/25)
Described herein are two different methods for the synthesis of vinyl halides by a shuttle catalysis based iridium-catalyzed transfer hydrohalogenation of unactivated alkynes. The use of 4-chlorobutan-2-one or tert-butyl halide as donors of hydrogen halides allows this transformation in the absence of corrosive reagents, such as hydrogen halides or acid chlorides, thus largely improving the functional-group tolerance and safety profile of these reactions compared to the state-of-the-art. This method has granted access to alkenyl halide compounds containing acid-sensitive groups, such as tertiary alcohols, silyl ethers, and acetals. The synthetic value of those methodologies has been demonstrated by gram-scale synthesis where low catalyst loading was achieved.
Synthesis of Eight-Membered Nitrogen Heterocycles via a Heterogeneous PtI2-Catalyzed Cascade Cycloaddition Reaction of δ-Aminoalkynes with Electron-Deficient Alkynes
Li, Xinhong,Wang, Songmeng,Wang, Hongkai,Wang, Weilin,Liu, Lingyan,Chang, Weixing,Li, Jing
supporting information, p. 1525 - 1531 (2020/03/23)
A novel heterogeneous PtI2-catalyzed cascade reaction of δ-aminoalkynes was developed for the synthesis of various eight-membered nitrogen heterocycles in excellent yields. The reaction proceeds via a hydration of δ-aminoalkynes and subsequent intramolecular cyclization and intermolecular addition as well as ring-expansion cascade reaction with another electron-deficient alkynes. This method has the advantages of simple operation and mild reaction conditions. And the simple PtI2 with no any supports could be readily recycled through simple centrifugation without substantial loss of activity in 1,2-dichloroethane (DCE). The recyclability of PtI2 may be ascribed to its insolubility in DCE. The reaction constitutes a formal [6+2]-cycloaddition. (Figure presented.).
Anodic oxidation of dithiane carboxylic acids: A rapid and mild way to access functionalized orthoesters
Denis, Camille,Dobbs, Adrian P.,Garcia, Anthony D.,Goodall, Iain C. A.,Lam, Kevin,Leech, Matthew C.,Petti, Alessia
supporting information, p. 4000 - 4005 (2020/06/08)
A new electrochemical methodology has been developed for the preparation of a wide variety of functionalized orthoesters under mild and green conditions from easily accessible dithiane derivatives. The new methodology also offers an unprecedented way to access tri(fluorinated) orthoesters, a class of compound that has never been studied before. This provides the community with a rapid and general method to prepare libraries of functionalized orthoesters from simple and readily available starting materials.
SMARCA DEGRADERS AND USES THEREOF
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Paragraph 00761; 00762, (2020/12/30)
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI/SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and/or polybromo-1 (PB-1) protein via ubiqitination and/or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and/or PB1 proteins.
Potent and Preferential Degradation of CDK6 via Proteolysis Targeting Chimera Degraders
Su, Shang,Yang, Zimo,Gao, Hongying,Yang, Haiyan,Zhu, Songbiao,An, Zixuan,Wang, Juanjuan,Li, Qing,Chandarlapaty, Sarat,Deng, Haiteng,Wu, Wei,Rao, Yu
supporting information, p. 7575 - 7582 (2019/08/20)
A focused PROTAC library hijacking cancer therapeutic target CDK6 was developed. A design principle as "match/mismatch" was proposed for understanding the degradation profile differences in these PROTACs. Notably, potent PROTACs with specific and remarkable CDK6 degradation potential were generated by linking CDK6 inhibitor palbociclib and E3 ligase CRBN recruiter pomalidomide. The PROTAC strongly inhibited proliferation of hematopoietic cancer cells including multiple myeloma and robustly degraded copy-amplified/mutated forms of CDK6, indicating future potential clinical applications.
Synthesis of a protected ribonucleoside phosphoramidite-linked spin label via an alkynyl chain at the 5′ position of uridine
Hatano, Akihiko,Terado, Nanae,Kanno, Yuichi,Nakamura, Toshikazu,Kawai, Gota
supporting information, p. 136 - 145 (2019/01/24)
New, spin-labeled nucleosides, and an efficient synthetic route for a modified uridine amidite, were developed. The spin-labeled part was the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) group, which was linked via an alkynyl chain at the 5 position of uridine. Three typical protecting groups, the t-butyldimethylsilyl (TBDMS) group at 2′, the dimethoxytrityl (DMTr) group at 5′, and the phosphoramidite group at 3′, were introduced to produce an automated nucleic acid synthesizer. The TEMPO group at the 5 position in the uridine structure affected introduction of bulky protecting groups, such as the DMTr group at the 5′ position and the TBDMS group at the 2′ position. The electron paramagnetic resonance (EPR) data revealed a nitroxyl radical in the structure of synthetic nucleoside compounds; however, RNA produced by automated synthesis using a TEMPO-linked uridine phosphoramidite building block was EPR silent.
RAF-DEGRADING CONJUGATE COMPOUNDS
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Paragraph 0209; 0399-0400, (2018/11/22)
The present disclosure provides, inter alia, RAF-Degrading Conjugate Compounds that are useful in the treatment of cancer and other RAF related diseases. Also provided are, pharmaceutical compositions, methods of treatment, and kits comprising a RAF- Degrading Conjugate Compound.
