- Synthetic method of pilosin B and intermediate pseudomonophenols thereof
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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.
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- Discovery of Anti-TNBC Agents Targeting PTP1B: Total Synthesis, Structure-Activity Relationship, in Vitro and in Vivo Investigations of Jamunones
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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.
- Hu, Caijuan,Li, Guoxun,Mu, Yu,Wu, Wenxi,Cao, Bixuan,Wang, Zixuan,Yu, Hainan,Guan, Peipei,Han, Li,Li, Liya,Huang, Xueshi
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p. 6008 - 6020
(2021/05/06)
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- Biomimetic total syntheses of baefrutones A-D, baeckenon B, and frutescones A, D-F
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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.
- Dong, Ying-Ying,Hou, Ji-Qin,Peng, Qiu-Shi,Wang, Hao,Yu, Jiang-Hong,Zhang, Bao-Bao,Zhao, Heng
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p. 1135 - 1139
(2020/02/22)
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- ADDITIVE COMPOSITION FOR CULTURE MEDIUM, ADDITIVE COMPOUND FOR CULTURE MEDIUM, AND METHOD FOR CULTURE OF CELLS OR TISSUE USING SAME
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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.}
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Paragraph 0088
(2020/06/15)
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- The First Racemic Total Syntheses of the Antiplasmodials Watsonianones A and B and Corymbone B
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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.
- Zhang, Xiao,Wu, Guiyun,Huo, Luqiong,Guo, Xueying,Qiu, Shengxiang,Liu, Hongxin,Tan, Haibo,Hu, Yingjie
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supporting information
p. 3 - 7
(2019/11/21)
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- Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity
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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.
- 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
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supporting information
(2020/05/25)
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- Synthesis and some properties of 2,4,6-trihydroxy-3-methylbenzoic acid
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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.
- Shubin,Bobylev,Kuznetsov,Ruchkina,Kobrakov
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- Novel diphenylmethyl compounds having mycobacterium tuberculosis inhibitory activity
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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.
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- Derivatives of Natural Product Agrimophol as Disruptors of Intrabacterial pH Homeostasis in Mycobacterium tuberculosis
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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.
- 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
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p. 1087 - 1104
(2019/05/22)
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- Total synthetic method of natural product pseudoaspidinol
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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.
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- Antifungal agents: Design, synthesis, antifungal activity and molecular docking of phloroglucinol derivatives
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Pseudoaspidinol is a phloroglucinol derivative with Antifungal activity and is a major active component of Dryopteris fragrans. In our previous work, we studied the total synthesis of pseudoaspidinol belonging to a phloroglucinol derivative and investigated its antifungal activity as well as its intermediates. However, the results showed these compounds have low antifungal activity. In this study, in order to increase antifungal activities of phloroglucinol derivatives, we introduced antifungal pharmacophore allylamine into the methylphloroglucinol. Meanwhile, we remained C1–C4 acyl group in C-6 position of methylphloroglucinol using pseudoaspidinol as the lead compound to obtain novel phloroglucinol derivatives, synthesized 17 compounds, and evaluated antifungal activities on Trichophyton rubrum and Trichophyton mentagrophytes in vitro. Molecular docking verified their ability to combine the protein binding site. The results indicated that most of the compounds had strong antifungal activity, in which compound 17 were found to be the most active on Trichophyton rubrum with Minimum Inhibitory Concentration (MIC) of 3.05 μg/mL and of Trichophyton mentagrophytes with MIC of 5.13 μg/mL. Docking results showed that compounds had a nice combination with the protein binding site. These researches could lay the foundation for developing antifungal agents of clinical value.
- Teng, Xingxing,Wang, Yuanyuan,Gu, Jinhua,Shi, Peiqi,Shen, Zhibin,Ye, Lianbao
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- A natural product yellow filicic acid BB of full-synthesis method
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The invention relates to a natural product yellow filicic acid BB of full-synthesis method, which belongs to the technical field of organic chemistry. The invention from the economic and easy to synthesize the phloroglucinol proceed double-acylated phloroglucinol, then after iodine methane-to-carbon double methylation, removing monomolecular acyl got the midbody 3; to phloroglucinol as raw materials, acetate acylation to obtain the aldehyde phloroglucinol, reduction of the aldehyde is methyl, then acylated to obtain intermediate 6; the two fragments obtained through the Eschenmoser's salt combined yellow filicic acid BB. In the method 42% overall yield of yellow filicic acid improves the BB fully synthetic yield, raw material economy are easy, simple operation, high yield, and suitable for production, may be its biological activity study provide a large number of raw materials.
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- Chemo-enzymatic Total Synthesis of Oxosorbicillinol, Sorrentanone, Rezishanones B and C, Sorbicatechol A, Bisvertinolone, and (+)-Epoxysorbicillinol
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The sorbicillinoids are a large family of fungal natural products, many of which possess highly challenging molecular architectures. Depending on their individual structures they exhibit strong biological activities ranging from radical scavenging and anti-infective properties to cytotoxicity. Despite the resulting strong biomedical potential of these natural products and the interest of synthetic chemists owing to their fascinating structures, many sorbicillinoids are currently not synthetically accessible, thus hampering in-depth biological characterization and structural diversification. By using recombinant oxidoreductase SorbC and readily accessible sorbicillin-type synthetic precursors, we have developed enantioselective, one-pot chemo-enzymatic routes to a broad range of sorbicillinoids, thereby establishing total syntheses of oxosorbicillinol, sorrentanone, rezishanones B and C, sorbicatechol A, bisvertinolone, and (+)-epoxysorbicillinol.
- Sib, Anna,Gulder, Tobias A. M.
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supporting information
p. 14650 - 14653
(2018/10/26)
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- Efficient synthesis of rottlerin and its two subunits
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Rottlerin, a natural product isolated from Mallotus philippensis, is associated with a range of biological activities. Its chemical structure is featured by two different substituted phloroglucinol units linked by a methylene group. In this study, we accomplished a total synthesis of rottlerin using phenol-aldehyde condensation as the key reaction. By our method, gram-scale preparation of the two structural subunits was achieved, and rottlerin was obtained in a longest eight linear step with 20% overall yield. Our study provides a practical solution for obtaining the sample of rottlerin in an efficient way.
- Li, Yangfeng,Yu, Biao,Wang, Renxiao
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p. 1856 - 1859
(2016/04/19)
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- Concise synthesis and cellular evaluation of 3′-formyl-4′,6′-dihydroxy-2′-methoxy-5′-methylchalcone (FMC) and its analogues
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3′-Formyl-4′,6′-dihydroxy-2′-methoxy-5′-methylchalcone (FMC) was a natural product isolated from Cleistocalyx operculatus. A four-step synthetic strategy toward FMC and its four analogues (1b-1e) was first developed. All compounds were synthesized from commercially available 2,4,6-trihydroxyacetophenone; formylation at 3′ position under Vilsmeier-Haack conditions was followed by the introduction of a methyl group at 5′ position. The key step of selective methylation at 2′ position was achieved by trimethylsilyldiazomethane (TMSCHN2). Then substituted aromatic aldehydes were condensed through Claisen-Schmidt reaction in the presence of potassium hydroxide. All structures were confirmed by 1H NMR, 13C NMR, and high-resolution mass spectra. FMC and analogues were screened for their antiproliferative activity.
- Zhuo, Xiang,En-Zhen, Li,Hai, Liang,Hong-Ju, Guo,Ning, Shi,Xue-Hui, Zhang,Qi-Fang, Qian,Jiu-Hong, Wu
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supporting information
p. 3139 - 3147
(2015/10/06)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- Biomimetic synthesis, antimicrobial, antileishmanial and antimalarial activities of euglobals and their analogues
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In the present communication, naturally occurring phloroglucinol- monoterpene adducts, euglobals G1-G4 (3b/a and 4a/b) and 16 new analogues (13a/b-18a/b and 19-22) were synthesized by biomimetic approach. These synthetic compounds differ from natural euglobals in the nature of monoterpene and acyl functionality. All of these compounds were evaluated for their antibacterial, antifungal, antileishmanial and antimalarial activities. Analogue 17b possessed good antibacterial activity against methicillin-resistant Staphylococcus aureus, while analogues 19-22 possessed potent antifungal activity against Candida glabrata with IC50s ranging from 1.5 to 2.5 μg/mL. Euglobals along with all synthesized analogues exhibited antileishmanial activity. Amongst these, euglobal G2 (3a), G3 (4a) and analogues 13a and 14a showed potent antileishmanial activity with IC50s ranging from 2.8 to 3.9 μg/mL. Analogue 16a possessed antimalarial activity against chloroquine sensitive D6 clone of Plasmodium falciparum. None of the compounds showed toxicity against mammalian kidney fibroblasts (vero cells) upto the concentration of 4.76 μg/ml.
- Bharate, Sandip B.,Bhutani, Kamlesh K.,Khan, Shabana I.,Tekwani, Babu L.,Jacob, Melissa R.,Khan, Ikhlas A.,Singh, Inder Pal
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p. 1750 - 1760
(2007/10/03)
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- Anti-AIDS agents 68. The first total synthesis of a unique potent anti-HIV chalcone from genus Desmos
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The first total synthesis of a unique highly functionalized and potent anti-HIV chalcone 1, isolated from genus Desmos, was achieved from commercially available 2,4,6-trihydroxytoluene (3) or 2,4,6-trihydroxybenzaldehyde (2) in five (from 3) or six steps (from 2).
- Nakagawa-Goto, Kyoko,Lee, Kuo-Hsiung
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p. 8263 - 8266
(2007/10/03)
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- An efficient two-step synthesis of jensenone isolated from Eucalyptus jensenii. Synthesis of analogues and evaluation as antioxidants
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A phloroglucinol derivative, jensenone (1) isolated from leaves of Eucalyptus jensenii has been synthesized for the first time through a short and efficient two-step procedure starting from commercially available phloroglucinol. The methodology provides a simplified route to introduce diformyl moiety for synthesis of biologically active formylated phloroglucinol compounds such as antimalarial robustadials, cancer chemopreventive euglobals, and antifouling sideroxylonals. Several analogues of jensenone have also been synthesized and evaluated for antioxidant capacity. CSIRO 2005.
- Bharate, Sandip B.,Chauthe, Siddheshwar K.,Bhutani, Kamlesh K.,Singh, Inder P.
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p. 551 - 555
(2007/10/03)
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- Five phloroglucinol-monoterpene adducts from Eucalyptus grandis
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Five new euglobals possessing the phloroglucinol-monoterpene structure, euglobals G8-G12, together with a known euglobal-IIc were isolated from the hexane fraction of the methanol extract of the leaves of Eucalyptus grandis. Euglobal-G8 is an adduct of formyl-isovaleroyl-phtoroglucinol and γ- terpinene whereas -G9, -G10 and -G11 have the same phloroglucinol moiety fused with α-terpinene, while Euglobal-G12 has terpinolene fused with the same phloroglucinol moiety. The structures of these compounds were elucidated on the basis of spectral evidences. Biomimetic synthesis of euglobals suggests that these compounds are derived biogenetically by the Diels-Alder type cycloaddition of the corresponding terpenes with an ortho-quinone methide generated from grandinol.
- Umehara, Kazuhiro,Singh, Inder Pal,Etoh, Hideo,Takasaki, Midori,Konoshima, Takao
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p. 1699 - 1704
(2007/10/03)
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- TWO AURONE GLYCOSIDES FROM THE FLOWERS OF PTEROCARPUS MARSUPIUM
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Two new aurone glycosides 4,6,4'-trihydroxy 6-O-rhamnopyranoside and 4,6,4'-trihydroxy-7-methylaurone 4-O-rhamnopyranoside have been isolated and identified from the flowers of Pterocarpus marsupium. - Keywords: Pterocarpus marsupium; Leguminosae; 4,6,4'-trihydroxyaurone 6-O-rhamnopyranoside; 4,6,4'-trihydroxy-7-methylaurone 4-O-rhamnopyranoside.
- Mohan, Poonam,Joshi, T.
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p. 1287 - 1288
(2007/10/02)
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- DEOXYGENATION OF ALDEHYDES AND KETONES WITH SODIUM CYANOBOROHYDRIDE
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Treatment of hydroxy-substituted aromatic aldehydes and ketones with sodium cyanoborohydride yields the corresponding methylene compounds under conditions which favor intermediate carbonium ion formation.
- Elliger, Carl A.
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p. 1315 - 1324
(2007/10/02)
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