69189-03-3Relevant academic research and scientific papers
Identification and Profiling of a Novel Diazaspiro[3.4]octane Chemical Series Active against Multiple Stages of the Human Malaria Parasite Plasmodium falciparum and Optimization Efforts
Le Manach, Claire,Dam, Jean,Woodland, John G.,Kaur, Gurminder,Khonde, Lutete P.,Brunschwig, Christel,Njoroge, Mathew,Wicht, Kathryn J.,Horatscheck, André,Paquet, Tanya,Boyle, Grant A.,Gibhard, Liezl,Taylor, Dale,Lawrence, Nina,Yeo, Tomas,Mok, Sachel,Eastman, Richard T.,Dorjsuren, Dorjbal,Talley, Daniel C.,Guo, Hui,Simeonov, Anton,Reader, Janette,Van Der Watt, Mari?tte,Erlank, Erica,Venter, Nelius,Zawada, Jacek W.,Aswat, Ayesha,Nardini, Luisa,Coetzer, Theresa L.,Lauterbach, Sonja B.,Bezuidenhout, Belinda C.,Theron, Anjo,Mancama, Dalu,Koekemoer, Lizette L.,Birkholtz, Lyn-Marie,Wittlin, Sergio,Delves, Michael,Ottilie, Sabine,Winzeler, Elizabeth A.,Smith, Dennis,Fidock, David A.,Street, Leslie J.,Basarab, Gregory S.,Duffy, James,Chibale, Kelly
, p. 2291 - 2309 (2021/03/01)
A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparum whole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure-activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparum cyclic amine resistance locus in the mode of resistance.
Butenolide derivative as well as preparation method and application thereof
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Paragraph 0045-0047; 0051, (2020/07/21)
The invention discloses a butenolide compound as well as a preparation method and an application thereof. The butenolide derivative has the inhibitory activity of protein tyrosine phosphatase 1B (PTP1B), improves insulin resistance of HepG2 cells, generates a remarkable hypoglycemic effect and can be used for preparing a medicine for treating diabetes mellitus.
Intermolecular Radical Addition to Ketoacids Enabled by Boron Activation
Xie, Shasha,Li, Defang,Huang, Hanchu,Zhang, Fuyuan,Chen, Yiyun
supporting information, p. 16237 - 16242 (2019/10/14)
The intermolecular radical addition to the carbonyl group is difficult due to the facile fragmentation of the resulting alkoxyl radical. To date, the intermolecular radical addition to ketones, a valuable approach to construct quaternary carbon centers, remains a formidable synthetic challenge. Here, we report the first visible-light-induced intermolecular alkyl boronic acid addition to α-ketoacids enabled by the Lewis acid activation. The in situ boron complex formation is confirmed by various spectroscopic measurements and mechanistic probing experiments, which facilitates various alkyl boronic acid addition to the carbonyl group and prevents the cleavage of the newly formed C-C bond. Diversely substituted lactates can be synthesized from readily available alkyl boronic acids and ketoacids at room temperature merely under visible light irradiation, without any additional reagent. This boron activation approach can be extended to alkyl dihydropyridines as radical precursors with external boron reagents for primary, secondary, and tertiary alkyl radical additions. The pharmaceutically useful anticholinergic precursors are easily scaled up in multigrams under metal-free conditions in flow reactors.
Synthesis of vulpinic and pulvinic acids from tetronic acid
Bourdreux, Yann,Bodio, Ewen,Willis, Catherine,Billaud, Célia,Le Gall, Thierry,Mioskowski, Charles
, p. 8930 - 8937 (2008/12/22)
A common precursor, tetronic acid, was used in the synthesis of several vulpinic acids and pulvinic acids, which are pigments found in several lichens and mushrooms. The key features of this method are a two-step alkylidenation of benzyl tetronate and a Suzuki-Miyaura cross-coupling. The synthesis of several natural products, vulpinic acid, pinastric acid, xerocomic acid is described.
