5389-87-7Relevant academic research and scientific papers
New Polyaminoisoprenyl Antibiotics Enhancers against Two Multidrug-Resistant Gram-Negative Bacteria from Enterobacter and Salmonella Species
Lieutaud, Aurélie,Pieri, Cyril,Bolla, Jean Michel,Brunel, Jean Michel
, p. 10496 - 10508 (2020)
A series consisting of new polyaminoisoprenyl derivatives were prepared in moderate to good chemical yields varying from 32 to 64% according to two synthetic pathways: (1) using a titanium-reductive amination reaction affording a 50/50 mixture of cis and trans isomers and (2) a direct nucleophilic substitution leading to a stereoselective synthesis of the compounds of interest. These compounds were then successfully evaluated for their in vitro antibiotic enhancer properties against resistant Gram-negative bacteria of four antibiotics belonging to four different families. The mechanism of action against Enterobacter aerogenes of one of the most efficient of these chemosensitizing agents was precisely evaluated by using fluorescent dyes to measure outer-membrane permeability and to determine membrane depolarization. The weak cytotoxicity encountered led us to perform an in vivo experiment dealing with the treatment of mice infected with Salmonella typhimurium and affording preliminary promising results in terms of tolerance and efficiency of the polyaminoisoprenyl derivative 5r/doxycycline combination.
Substrate specificities of wild and mutated farnesyl diphosphate synthases from Bacillus stearothermophilus with artificial substrates
Nagaki, Masahiko,Nakada, Minori,Musashi, Tohru,Kawakami, Jun,Ohya, Norimasa,Kurihara, Masayo,Maki, Yuji,Nishino, Tokuzo,Koyama, Tanetoshi
, p. 1657 - 1662 (2007)
To determine the substrate specificities of wild and mutated types of farnesyl diphosphate (FPP) synthases from Bacillus stearothermophilus, we examined the reactivities of 8-hydroxygeranyl diphosphate (HOGPP) and 8-methoxygeranyl diphosphate (CH3OGPP) as allylic substrate homologs. The wild-type FPP synthase reaction of HOGPP (and CH3OGPP) with isopentenyl diphosphate (IPP) gave hydroxyfarnesyl-(and methoxyfarnesyl-) diphosphates that stopped at the first stage of condensation. On the other hand, with mutated type FPP synthase (Y81S), the former gave hydroxygeranylgeranyl diphosphate as the main double-condensation product together with hydroxyfarnesyl diphosphate as a single-condensation product and a small amount of hydroxygeranylfarnesyl diphosphate as a triple-condensation product. Moreover, the latter gave a double-condensation product, methoxygeranylgeranyl diphosphate, as the main product and only a trace of methoxyfarnesyl diphosphate was obtained.
Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A
Liang, Xin-Ting,Sun, Bao-Chuan,Liu, Chang,Li, Yuan-He,Zhang, Nan,Xu, Qian-Qian,Zhang, Zhong-Chao,Han, Yi-Xin,Chen, Jia-Hua,Yang, Zhen
, p. 2135 - 2157 (2021/02/01)
A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson-Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13(R)-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (-)-spirochensilide A.
Compound with glucose-reducing and lipid-regulating effects as well as preparation and application thereof
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Paragraph 0020-0022, (2021/03/13)
The invention discloses a compound with glucose-reducing and lipid-regulating effects as well as a preparation and application thereof. The compound with glucose-reducing and lipid-regulating effectsis a compound with structures as shown in a formula I and a formula II and a pharmaceutically acceptable salt, wherein the structures as shown in the formula I and the formula II are specifically shown in the specification. The preparation is a tablet, a capsule, powder, a pill or an injection prepared by adding pharmaceutically acceptable auxiliary materials into the compound with the glucose-reducing and lipid-regulating effects. The application is the application of the compound with the glucose-reducing and lipid-regulating effects in preparing an FFA1/PPARdelta dual agonist. The application is the application of the compound with the glucose-reducing and lipid-regulating effects in preparation of drugs for preventing and/or treating glucose metabolic disorder and/or lipid metabolic disorder diseases. The compound and the medicinal salt thereof can be potentially used for treating or preventing diabetes, hyperlipidemia, fatty liver and other related metabolic syndromes, and have wide development prospects.
Construction of Pentacyclic Limonoid Skeletons via Radical Cascade Reactions
Mutoh, Hiroyuki,Nakamura, Shu,Hagiwara, Koichi,Inoue, Masayuki
, p. 6869 - 6878 (2021/05/29)
Limonoids 1 and 2 share a 6/6/6/5-membered ABCD-ring system and a six-membered oxacycle and differ in their C9-stereochemistries. A new radical-based strategy was devised to construct the pentacyclic skeletons of 1 and 2. An oxacycle-fused A-ring and enyne fragments were coupled to produce radical precursors 4a-4c with different C7-oxygen functionalities. The bridgehead tertiary bromide of 4a-4c participated in a radical cascade reaction with the three unsaturated bonds to cyclize the C9-diastereomeric BCD-rings.
A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols
Munyemana, Fran?ois,Patiny, Luc,Ghosez, Léon
, (2021/06/07)
A study of the deoxyhalogenation of allylic and propargylic alcohols with tetramethyl-α-halo-enamines is reported. Primary allylic and primary and secondary propargylic alcohols gave the corresponding halides in high yields. Secondary allylic and propargylic alcohols yielded the corresponding secondary halides but the reaction also produced some rearranged primary halides (I > Br > Cl). The reactions with tertiary allylic and tertiary propargylic alcohols gave several products and was therefore of little synthetic value. However, the addition of triethylamine to the reaction mixture or the use of lithium alkoxide instead of alcohol brought about a major change of the course of the reaction which led to amides carrying an allyl or an allenyl group at C2. This was shown to result from a Claisen-Eschenmoser rearrangement of an intermediate α-allyloxy- or propargyloxy-enamine.
Water-soluble meroterpenes containing an aminoglyceride fragment with geraniol residues: synthesis and membranotropic properties
Akhmedov, Alan A.,Shurpik, Dmitry N.,Plemenkov, Vitaliy V.,Stoikov, Ivan I.
, p. 29 - 31 (2019/02/19)
A number of new membrane anchors based on water-soluble aminoglycerides with geraniol fragments have been synthesized. A biomimetic approach was used based on the design of meroterpenes structurally similar to archaeal lipids. Turbidimetry and laser Doppler microelectrophoresis showed that the synthesized compounds were incorporated into unilamellar dipalmitoylphosphatidylcholine (DPPC) vesicles.
Repositioning Salirasib as a new antimalarial agent
Porta, Exequiel O. J.,Bofill Verdaguer, Ignasi,Perez, Consuelo,Banchio, Claudia,Ferreira De Azevedo, Mauro,Katzin, Alejandro M.,Labadie, Guillermo R.
, p. 1599 - 1605 (2019/09/30)
Malaria is a serious tropical disease that kills thousands of people every year, mainly in Africa, due to Plasmodium falciparum infections. Salirasib is a promising cancer drug candidate that interferes with the post-translational modification of Ras. This S-farnesyl thiosalicylate inhibits isoprenylcysteine carboxyl methyltransferase (ICMT), a validated target for cancer drug development. There is a high homology between the human and the parasite enzyme isoforms, in addition to being a druggable target. Looking to repurpose its structure as an antimalarial drug, a collection of S-substituted derivatives of thiosalicylic acid were prepared by introducing 1,2,3-triazole as a diversity entry point or by direct alkylation of the thiol. We further investigated the in vitro toxicity of FTS analogues to Plasmodium falciparum in the asexual stages and in Vero cells. An antiplasmodial activity assay was performed using a simple, high-sensitivity methodology based on nanoluciferase (NLuc)-transfected P. falciparum parasites. The results showed that some of the analogs were active at low micromolar concentration, including Salirasib. The most potent member of the series has S-farnesyl and the 1,2,3-triazole moiety substituted with phytyl. However, the compound substituted with methyl-naphthyl shows promising physicochemical and activity values. The low cytotoxicity in eukaryotic cells of the most active analogs provided good therapeutic indices, being starting-point candidates for future antimalarial drug development.
Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
supporting information, p. 2980 - 2983 (2018/05/28)
A practical method for the nucleophilic substitution (SN) of alcohols furnishing alkyl chlorides, bromides, and iodides under stereochemical inversion in high catalytic efficacy is introduced. The fusion of diethylcyclopropenone as a simple Lewis base organocatalyst and benzoyl chloride as a reagent allows notable turnover numbers up to 100. Moreover, the use of plain acetyl chloride as a stoichiometric promotor in an invertive SN-type transformation is demonstrated for the first time. The operationally straightforward protocol exhibits high levels of stereoselectivity and scalability and tolerates a variety of functional groups.
Structural Modification of Natural Product Ganomycin i Leading to Discovery of a α-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and Metabolic Dysfunction in Vivo
Wang, Kai,Bao, Li,Zhou, Nan,Zhang, Jinjin,Liao, Mingfang,Zheng, Zhongyong,Wang, Yujing,Liu, Chang,Wang, Jun,Wang, Lifeng,Wang, Wenzhao,Liu, Shuangjiang,Liu, Hongwei
, p. 3609 - 3625 (2018/05/01)
It is a great challenge to develop drugs for treatment of metabolic syndrome. With ganomycin I as a leading compound, 14 meroterpene derivatives were synthesized and screened for their α-glucosidase and HMG-CoA reductase inhibitory activities. As a result, a α-glucosidase and HMG-CoA reductase dual inhibitor ((R,E)-5-(4-(tert-butyl)phenyl)-3-(4,8-dimethylnona-3,7-dien-1-yl)furan-2(5H)-one, 7d) with improved chemical stability and long-term safety was obtained. Compound 7d showed multiple and strong in vivo efficacies in reducing weight gain, lowering HbAlc level, and improving insulin resistance and lipid dysfunction in both ob/ob and diet-induced obesity (DIO) mice models. Compound 7d was also found to reduce hepatic steatosis in ob/ob model. 16S rRNA gene sequencing, SCFA, and intestinal mucosal barrier function analysis indicated that gut microbiota plays a central and causative role in mediating the multiple efficacies of 7d. Our results demonstrate that 7d is a promising drug candidate for metabolic syndrome.
