88-03-9Relevant academic research and scientific papers
Synthetic method of pilosin B and intermediate pseudomonophenols thereof
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Paragraph 0034; 0067-0068, (2021/11/26)
The invention discloses a method for synthesizing pilosin B and intermediate pseudomonophenols thereof. The synthesis method of the pseudo-sheep equol comprises the step E. Step F and Step g. The synthetic method of the pilosin B provided by the invention is prepared by the following steps H, step J, preparation of the pseudomonophenols synthesized by the above method, and preparation of the pseudomonophenols synthesized by the method in step I. In step E, the novel amino protecting reagent with good reaction with the phenolic hydroxyl group is used as a protecting reagent, the phenol hydroxyl group of each intermediate in the intermediate molecule fragment a synthesis process is selectively protected, the reagent types are reduced and the use of toxic reagents such as benzyl chloride and the like is avoided.
Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, in Vitro and in Vivo Investigations of Jamunones
Hu, Caijuan,Li, Guoxun,Mu, Yu,Wu, Wenxi,Cao, Bixuan,Wang, Zixuan,Yu, Hainan,Guan, Peipei,Han, Li,Li, Liya,Huang, Xueshi
supporting information, p. 6008 - 6020 (2021/05/06)
Twenty-three natural jamunone analogues along with a series of jamunone-based derivatives were synthesized and evaluated for their inhibitory effects against breast cancer (BC) MDA-MB-231 and MCF-7 cells. The preliminary structure-activity relationship revealed that the length of aliphatic side chain and free phenolic hydroxyl group at the scaffold played a vital role in anti-BC activities and the methyl group on chromanone affected the selectivity of molecules against MDA-MB-231 and MCF-7 cells. Among them, jamunone M (JM) was screened as the most effective anti-triple-negative breast cancer (anti-TNBC) candidate with a high selectivity against BC cells over normal human cells. Mechanistic investigations indicated that JM could induce mitochondria-mediated apoptosis and cause G0/G1 phase arrest in BC cells. Furthermore, JM significantly restrained tumor growth in MDA-MB-231 xenograft mice without apparent toxicity. Interestingly, JM could downregulate phosphatidylinositide 3-kinase (PI3K)/Akt pathway by suppressing protein-tyrosine phosphatase 1B (PTP1B) expression. These findings revealed the potential of JM as an appealing therapeutic drug candidate for TNBC.
ADDITIVE COMPOSITION FOR CULTURE MEDIUM, ADDITIVE COMPOUND FOR CULTURE MEDIUM, AND METHOD FOR CULTURE OF CELLS OR TISSUE USING SAME
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Paragraph 0088, (2020/06/15)
The present invention provides a medium additive composition containing a compound represented by the following formula (I), or a salt thereof: {wherein each symbol is as defined in the DESCRIPTION.}
Biomimetic total syntheses of baefrutones A-D, baeckenon B, and frutescones A, D-F
Dong, Ying-Ying,Hou, Ji-Qin,Peng, Qiu-Shi,Wang, Hao,Yu, Jiang-Hong,Zhang, Bao-Bao,Zhao, Heng
supporting information, p. 1135 - 1139 (2020/02/22)
Biomimetic total syntheses of baefrutones A-D (1-4), baeckenon B (5), and frutescones A, D-F (6-9), isolated from the leaves of Baeckea frutescens, were achieved in 9, 8, and 5 steps, respectively, in moderate to good yields (72-83%). The synthetic routes feature the Michael addition, oxidative [4 + 2] cycloaddition, and water-promoted Diels-Alder click reactions as the key steps. This study helped gain thorough mechanistic insights into the biosynthetic origins and provided a facile approach for the construction of a library of natural tasmanone-based meroterpenoid analogues. Moreover, compounds 1-9 show potent inhibitory effects against S. paratyphi and/or C. albicans with MIC values of 3.125-25 μg mL-1, and they could be promising lead molecules for the design of new antibiotic agents.
The First Racemic Total Syntheses of the Antiplasmodials Watsonianones A and B and Corymbone B
Zhang, Xiao,Wu, Guiyun,Huo, Luqiong,Guo, Xueying,Qiu, Shengxiang,Liu, Hongxin,Tan, Haibo,Hu, Yingjie
supporting information, p. 3 - 7 (2019/11/21)
The first biomimetic total syntheses of three biologically meaningful acylphloroglucinols, watsonianones A and B and corymbone B, with potent antiplasmodial activity, were performed. Their total syntheses were carried out through a diversity-oriented synthetic strategy from congener 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione with high step efficiency. The spontaneous enolization/air oxidation of the precursor 2,2,4,4-tetramethyl-6-(3-methylbutylidene)cyclohexane-1,3,5-trione through a singlet O2-induced Diels-Alder reaction pathway to assemble the key biosynthetic peroxide intermediate is also discussed.
Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity
K?rber, Florian,Lübke, Marco,Le Quoc, Thang,Müller, Jasmin,Matschke, Veronika,Scherkenbeck, Jürgen,Schreiber, Julian A.,Schubert, Janina,Seebohm, Guiscard,Sivanathan, Sivatharushan,Strutz-Seebohm, Nathalie
supporting information, (2020/05/25)
The slow delayed rectifier potassium current (IKs) is formed by the KCNQ1 (Kv7.1) channel, an ion channel of four α-subunits that modulates KCNE1 β-subunits. IKs is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac IKs cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates IKs and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved IKs activators as novel therapeutics for the treatment of LQTS.
Synthesis and some properties of 2,4,6-trihydroxy-3-methylbenzoic acid
Shubin,Bobylev,Kuznetsov,Ruchkina,Kobrakov
, p. 74 - 78 (2019/04/25)
2,4,6-Trihydroxy-3-methylbenzoic acid was obtained by NaHCO3 carboxylation of 2,4,6-trihydroxytoluene. The heterocyclization and esterification of the above acid were studied.
Novel diphenylmethyl compounds having mycobacterium tuberculosis inhibitory activity
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Paragraph 0270; 0271; 0274; 0275, (2019/02/13)
The invention relates to novel diphenylmethyl derivatives having mycobacterium tuberculosis inhibitory activity and a preparation method thereof and particularly relates novel diphenylmethyl derivatives having activity for inhibiting replicative and non-replicating mycobacterium tuberculosis and a preparation method thereof. In particular, the invention relates to compounds shown in the formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof, wherein the variables are as described in the specification. The invention also relates to the preparation method of the compounds and their pharmaceutical compositions and a use of the compounds in preparation of drugs for treating mycobacterium tuberculosis infection-caused diseases.
Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis
Wu, Jie,Mu, Ran,Sun, Mingna,Zhao, Nan,Pan, Miaomiao,Li, Hongshuang,Dong, Yi,Sun, Zhaogang,Bai, Jie,Hu, Minwan,Nathan, Carl F.,Javid, Babak,Liu, Gang
, p. 1087 - 1104 (2019/05/22)
This article reports the rational medicinal chemistry of a natural product, agrimophol (1), as a new disruptor of intrabacterial pH (pHIB) homeostasis in Mycobacterium tuberculosis (Mtb). Through the systematic investigation of the structure-activity relationship of 1, scaffold-hopping of the diphenylmethane scaffold, pharmacophore displacement strategies, and studies of the structure-metabolism relationship, a new derivative 5a was achieved. Compound 5a showed 100-fold increased potency in the ability to reduce pHIB to pH 6.0 and similarly improved mycobactericidal activity compared with 1 against both Mycobacterium bovis-BCG and Mtb. Compound 5a possessed improved metabolic stability in human liver microsomes and hepatocytes, lower cytotoxicity, higher selectivity index, and similar pKa value to natural 1. This study introduces a novel scaffold to an old drug, resulting in improved mycobactericidal activity through decreasing pHIB, and may contribute to the critical search for new agents to overcome drug resistance and persistence in the treatment of tuberculosis.
Total synthetic method of natural product pseudoaspidinol
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Paragraph 0017, (2019/01/07)
The invention relates to a total synthetic method of a natural product pseudoaspidinol, belonging to the technical field of organic chemistry. The method comprises the steps of carrying out Vilsmeier-Haaucf reaction on economic and easily-available phloroglucinol dehydrate so as to obtain aldehyde-base phloroglucinol, carrying out Clemmensen reduction so as to obtain methyl phloroglucinol, carrying out Friedel-Crafts acylation so as to obtain lysine butyrylation methyl phloroglucinol, carrying out selective protection through ester groups, and carrying out methylation and deprotection, so as to obtain pseudoaspidinol. The total synthetic method has the beneficial effects that the total synthesis yield of pseudoaspidinol is increased at the total yield of 51%, the raw materials are economicand easily available, the operation is simple, the yield is relatively high, and a large number of raw materials are provided for the biological activity research of pseudoaspidinol.
