- New Polyaminoisoprenyl Antibiotics Enhancers against Two Multidrug-Resistant Gram-Negative Bacteria from Enterobacter and Salmonella Species
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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.
- Lieutaud, Aurélie,Pieri, Cyril,Bolla, Jean Michel,Brunel, Jean Michel
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Read Online
- Substrate specificities of wild and mutated farnesyl diphosphate synthases from Bacillus stearothermophilus with artificial substrates
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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.
- Nagaki, Masahiko,Nakada, Minori,Musashi, Tohru,Kawakami, Jun,Ohya, Norimasa,Kurihara, Masayo,Maki, Yuji,Nishino, Tokuzo,Koyama, Tanetoshi
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Read Online
- Asymmetric Total Synthesis of (-)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A
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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.
- 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
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p. 2135 - 2157
(2021/02/01)
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- Compound with glucose-reducing and lipid-regulating effects as well as preparation and application thereof
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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.
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Paragraph 0020-0022
(2021/03/13)
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- Construction of Pentacyclic Limonoid Skeletons via Radical Cascade Reactions
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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.
- Mutoh, Hiroyuki,Nakamura, Shu,Hagiwara, Koichi,Inoue, Masayuki
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p. 6869 - 6878
(2021/05/29)
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- A mild method for the replacement of a hydroxyl group by halogen: 3. the dichotomous behavior of α-haloenamines towards allylic and propargylic alcohols
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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.
- Munyemana, Fran?ois,Patiny, Luc,Ghosez, Léon
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- Water-soluble meroterpenes containing an aminoglyceride fragment with geraniol residues: synthesis and membranotropic properties
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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.
- Akhmedov, Alan A.,Shurpik, Dmitry N.,Plemenkov, Vitaliy V.,Stoikov, Ivan I.
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- Repositioning Salirasib as a new antimalarial agent
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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.
- Porta, Exequiel O. J.,Bofill Verdaguer, Ignasi,Perez, Consuelo,Banchio, Claudia,Ferreira De Azevedo, Mauro,Katzin, Alejandro M.,Labadie, Guillermo R.
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p. 1599 - 1605
(2019/09/30)
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- Nucleophilic Substitutions of Alcohols in High Levels of Catalytic Efficiency
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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.
- Stach, Tanja,Dr?ger, Julia,Huy, Peter H.
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supporting information
p. 2980 - 2983
(2018/05/28)
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- Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols
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Herein, a method for the nucleophilic substitution (SN) of benzyl alcohols yielding chloro alkanes is introduced that relies on aromatic sulfoxides as Lewis base catalysts (down to 1.5 mol-%) and benzoyl chloride (BzCl) as reagent. A systematic screening of various sulfoxides and other sulfinyl containing Lewis bases afforded (2-methoxyphenyl)methyl sulfoxide as optimal catalyst. In contrast to reported formamide catalysts, sulfoxides also enable the application of plain acetyl chloride (AcCl) as reagent. In addition, it was demonstrated that weakly electrophilic carboxylic acid chlorides like BzCl promote Pummerer rearrangement of sulfoxides already at room temperature. This side-reaction also provided the explanation, why sulfoxide catalyzed SN-reactions of alcohols do not allow the effective production of aliphatic and electron deficient chloro alkanes. Comparison experiments provided further insight into the reaction mechanism.
- Motsch, Sebastian,Schütz, Christian,Huy, Peter H.
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supporting information
p. 4541 - 4547
(2018/09/13)
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- A General Catalytic Method for Highly Cost- and Atom-Efficient Nucleophilic Substitutions
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A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold SN2 inversion, which demonstrates the high practical value of the presented method.
- Huy, Peter H.,Filbrich, Isabel
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supporting information
p. 7410 - 7416
(2018/04/30)
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- 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
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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.
- 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
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p. 3609 - 3625
(2018/05/01)
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- METHOD OF CONVERTING ALCOHOL TO HALIDE
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The present invention relates to a method of converting an alcohol into a corresponding halide. This method comprises reacting the alcohol with an optionally substituted aromatic carboxylic acid halide in presence of an N-substituted formamide to replace a hydroxyl group of the alcohol by a halogen atom. The present invention also relates to a method of converting an alcohol into a corresponding substitution product. The second method comprises: (a) performing the method of the invention of converting an alcohol into the corresponding halide; and (b) reacting the corresponding halide with a nucleophile to convert the halide into the nucleophilic substitution product.
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Page/Page column 106; 107
(2017/01/02)
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- Formamides as Lewis Base Catalysts in SNReactions—Efficient Transformation of Alcohols into Chlorides, Amines, and Ethers
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A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.
- Huy, Peter H.,Motsch, Sebastian,Kappler, Sarah M.
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supporting information
p. 10145 - 10149
(2016/08/16)
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- Novel (E)-β-farnesene analogues containing 2-nitroiminohexahydro-1,3,5-triazine: Synthesis and biological activity evaluation
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In order to discover novel eco-friendly compounds with good activity for aphid control, (E)-β-farnesene (EβF), the main component of the aphid alarm pheromone, was chosen as the lead compound. By introducing a 2-nitroimino-hexahydro-1,3,5-triazine moiety (abbreviated NHT) to replace the unstable conjugated double bond system of EβF, a series of novel EβF analogues containing the NHT moiety were synthesized via the reaction of substituted NHT rings with (E)-1-chloro-3,7-dimethylocta-2,6-diene. All the compounds were characterized by 1H-NMR, 13C-NMR, IR, and high resolution mass spectroscopy (HRMS). The bioassay results showed that all the analogues displayed different repellent and aphicidal activities against green peach aphid (Myzus persicae). Particularly, the analogue 4r exhibited obvious repellent activity (repellent proportion: 78.43%) and similar aphicidal activity against M. persicae (mortality: 82.05%) as the commercial compound pymetrozine (80.07%). A preliminary structure-activity relationship (SAR) study was also performed, which offered valuable clues for the design of further new EβF analogues.
- Qin, Yaoguo,Zhang, Jingpeng,Song, Dunlun,Duan, Hongxia,Li, Wenhao,Yang, Xinling
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- Computer-aided rational design of novel EBF analogues with an aromatic ring
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Odorant binding proteins (OBPs) are important in insect olfactory recognition. These proteins bind specifically to insect semiochemicals and induce their seeking, mating, and alarm behaviors. Molecular docking and molecular dynamics simulations were performed to provide computational insight into the interaction mode between AgamOBP7 and novel (E)-β-farnesene (EBF) analogues with an aromatic ring. The ligand-binding cavity in OBP7 was found to be mostly hydrophobic due to the presence of several nonpolar residues. The interactions between the EBF analogues and the hydrophobic residues in the binding cavity increased in strength as the distance between them decreased. The EBF analogues with an N-methyl formamide or ester linkage had higher docking scores than those with an amide linkage. Moreover, delocalized π–π and electrostatic interactions were found to contribute significantly to the binding between the ligand benzene ring and nearby protein residues. To design new compounds with higher activity, four EBF analogues D1–D4 with a benzene ring were synthesized and evaluated based on their docking scores and binding affinities. D2, which had an N-methyl formamide group linkage, exhibited stronger binding than D1, which had an amide linkage. D4 exhibited particularly strong binding due to multiple hydrophobic interactions with the protein. This study provides crucial foundations for designing novel EBF analogues based on the OBP structure. [Figure not available: see fulltext.]
- Wang, Shanshan,Sun, Yufeng,Du, Shaoqing,Qin, Yaoguo,Duan, Hongxia,Yang, Xinling
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- α-Selective Allylation of Isatin Imines Using Metallic Barium
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The Barbier-type allylation of isatin imines with allylic chlorides was achieved by using metallic barium as the promoter. Various α-allylated 3-amino-2-oxindoles were synthesized from the corresponding allylic chlorides and isatin imines. The double-bond geometry of allylic chlorides was retained throughout the reaction. An arylic bromide or iodide functionality of the products was robust to metalation under the optimum reaction conditions.
- Yanagisawa, Akira,Yamafuji, Seiya,Sawae, Toshiki
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supporting information
p. 2019 - 2023
(2016/08/09)
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- Copper-catalyzed enantioselective allylic cross-coupling with alkylboranes
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Abstract We have presented full details of our work on alkylboranes, which we have introduced as new reagents for copper-catalyzed SN2′-type enantioselective allylic substitutions. The copper catalysis delivered enantioenriched chiral products containing tertiary or quaternary carbon stereogenic centers branched with functionalized sp3-alkyl groups. The wide availability of alkylboranes via the established alkene hydroboration reaction is an attractive feature of these transformations. Various functional groups are tolerated in the substrates. A reaction pathway involving addition-elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.
- Hojoh, Kentaro,Shido, Yoshinori,Nagao, Kazunori,Mori, Seiji,Ohmiya, Hirohisa,Sawamura, Masaya
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p. 6519 - 6533
(2015/08/18)
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- Total Synthesis of Limonin
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Limonoids are highly oxygenated C13α-triterpenes and common secondary metabolites. Several hundred congeners have been isolated to date. The first total synthesis of (±)-limonin, the flagship congener of the limonoids, is now reported and features 1) a tandem radical cyclization generating the BCD ring system with the C13α configuration that is essential to the limonoids and a Robinson annulation to construct the limonoid androstane framework, 2) a singlet-oxygen cycloaddition and a Baeyer-Villiger oxidation to synthesize the highly oxidized D ring, and 3) a Surez reaction to construct the unique AA′ ring system.
- Yamashita, Shuji,Naruko, Akito,Nakazawa, Yuki,Zhao, Le,Hayashi, Yujiro,Hirama, Masahiro
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supporting information
p. 8538 - 8541
(2015/11/27)
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- Concise syntheses and biological activities of ganomycin I and fornicin A
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The first enantioselective syntheses of ganomycin I, a meroterpenoid isolated from the Vietnamese mushroom Ganoderma colossum, and the related meroterpenoid fornicin A were accomplished. Our methodology for the total syntheses of these compounds featured the construction of the butenolide moiety by asymmetric dihydroxylation followed by Julia-Kocienski type olefin formation and ring-closing metathesis reactions. The absolute configurations of the two natural products were determined by comparisons of specific rotation. A cell-based assay of the synthetic compounds with transfected human embryonic kidney 293 tetoff (E-PR293) cells indicated that ganomycin I possesses cytotoxicity and fornicin A possesses weak anti-HIV-1 protease activity without cytotoxicity.
- Yajima, Arata,Urao, Shota,Katsuta, Ryo,Nukada, Tomoo
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p. 731 - 738
(2014/03/21)
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- ISOPRENE OLIGOMER, POLYISOPRENE, PROCESSES FOR PRODUCING THESE MATERIALS, RUBBER COMPOSITION, AND PNEUMATIC TIRE
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The invention relates to an isoprene oligomer that contains a trans structural moiety and a cis structural moiety, which can be represented by the following formula (1), wherein at least 1 atom or group in the trans structural moiety is replaced by another atom or group. The invention also relates to a polyisoprene, which is biosynthesized using the isoprene oligomer and isopentenyl diphosphate. Further, this invention provides a rubber composition comprising the isoprene oligomer and/or the polyisoprene, and a pneumatic tire, including tire components (e.g., treads and sidewalls) formed from the rubber composition. wherein n represents an integer from 1 to 10; m represents an integer from 1 to 30; and Y represents a hydroxy group, a formyl group, a carboxy group, an ester group, a carbonyl group, or a group represented by the following formula (2):
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Paragraph 267
(2014/06/25)
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- Construction of quaternary stereogenic carbon centers through copper-catalyzed enantioselective allylic cross-coupling with alkylboranes
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A combination of an in situ generated chiral CuI/DTBM-MeO-BIPHEP catalyst system and EtOK enabled the enantioselective SN2'-type allylic cross-coupling between alkylborane reagents and γ,γ- disubstituted primary allyl chlorides with enantiocontrol at a useful level. The reaction generates a stereogenic quaternary carbon center having three sp 3-alkyl groups and a vinyl group. This protocol allowed the use of terminal alkenes as nucleophile precursors, thus representing a formal reductive allylic cross-coupling of terminal alkenes. A reaction pathway involving addition/elimination of a neutral alkylcopper(I) species with the allyl chloride substrate is proposed.
- Hojoh, Kentaro,Shido, Yoshinori,Ohmiya, Hirohisa,Sawamura, Masaya
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supporting information
p. 4954 - 4958
(2014/05/20)
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- Concise Syntheses and Biological Activities of Ganomycin i and Fornicin A
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The first enantioselective syntheses of ganomycin I, a meroterpenoid isolated from the Vietnamese mushroom Ganoderma colossum, and the related meroterpenoid fornicin A were accomplished. Our methodology for the total syntheses of these compounds featured the construction of the butenolide moiety by asymmetric dihydroxylation followed by Julia-Kocienski type olefin formation and ring-closing metathesis reactions. The absolute configurations of the two natural products were determined by comparisons of specific rotation. A cell-based assay of the synthetic compounds with transfected human embryonic kidney 293 tet-off (E-PR293) cells indicated that ganomycin I possesses cytotoxicity and fornicin A possesses weak anti-HIV-1 protease activity without cytotoxicity.
- Yajima, Arata,Urao, Shota,Katsuta, Ryo,Nukada, Tomoo
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p. 731 - 738
(2015/10/05)
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- Efficient procedures to prepare primary and secondary alkyl halides from alkanols via the corresponding sulfonates under mild conditions
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The study presented herein shows that sulfonate/halide exchange can be advantageously performed in THF to avoid several side reactions such as elimination and epimerization when the reaction is performed from a chiral alkyl sulfonate or a substrate having a C-H acidic chiral center. The main limitation of this procedure was found to be the conversion of secondary alkyl sulfonates to alkyl chlorides. In this case, the addition of a catalytic amount of manganese chloride clearly accelerates the rate and the efficiency of the reaction. Copyright
- Cahiez, Gerard,Gager, Olivier,Moyeux, Alban,Delacroix, Thomas
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supporting information; experimental part
p. 1519 - 1528
(2012/07/03)
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- Allylic and allenic halide synthesis via NbCl5- and NbBr 5-mediated alkoxide rearrangements
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(Chemical Equation Presented) Addition of NbCl5 or NbBr 5 to a series of magnesium, lithium, or potassium allylic or propargylic alkoxides directly provides allylic or allenic halides. Halogenation formally occurs through a metallahalo-[3,3] rearrangement, although concerted, ionic, and direct displacement mechanisms appear to operate competitively. Transposition of the olefin is equally effective for allylic alkoxides prepared by nucleophilic addition, deprotonation, or reduction. Experimentally, the niobium pentahalide halogenations are rapid, afford essentially pure (E)-allylic or -allenic halides after extraction, and are applicable to a range of aliphatic and aromatic alcohols, aldehydes, and ketones. 2009 American Chemical Society.
- Ravikumar,Yao, Lihua,Fleming, Fraser F.
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supporting information; experimental part
p. 7294 - 7299
(2010/01/16)
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- Asymmetric dihydroxylation of β,γ-unsaturated carboxylic esters with trisubstituted C=C bonds - Enantioselective syntheses of trisubstituted γ-butyrolactones
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β,γ-Unsaturated esters with stereodefined trisubstitued C=C double bonds were prepared by the Arndt-Eistert homologation of α,β-unsaturated carboxyl halides, by two-step methoxycarbonylation of allylbarium reagents, by deconjugation of α,β-unsaturated esters, and by Horner-Wadsworth-Emmons variants of the Stobbe condensation. Sharpless asymmetric dihydroxylation of the β,γ-unsaturated esters, followed by spontaneous cyclization, afforded β-hydroxy-γ-lactones in moderate to good yields and with enantiomeric excesses of up to 97 %. Similarly, tetrahydroxy-γ-lactones were obtained from diunsaturated esters; these lactones were converted into a bislactone and an unsaturated β-hydroxy γ-lactone. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Kapferer, Tobias,Brueckner, Reinhard
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p. 2119 - 2133
(2007/10/03)
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- A convenient method for the preparation of primary amines using tritylamine
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A simple method for the preparation of primary amines by treating N-tritylamines with trifluoroacetic acid has been established. The N-tritylamines were prepared by the reaction of alkyl halides or alkyl p-toluenesulfonates with tritylamine, or by the reaction of alkyl bromides with lithium tritylamide.
- Theodorou, Vassiliki,Ragoussis, Valentine,Strongilos, Alexandros,Zelepos, Evangelos,Eleftheriou, Argyro,Dimitriou, Maria
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p. 1357 - 1360
(2007/10/03)
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- Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing the halimane skeleton
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The cloning and functional expression of Mycobacterium tuberculosis Rv3377c in Escherichia coli revealed that this gene encodes the diterpene cyclase for producing (+)-5(6),13-halimadiene-15-ol, which accepts geranylgeranyldiphosphate as the intrinsic substrate. The Royal Society of Chemistry 2005.
- Nakano, Chiaki,Okamura, Tomoo,Sato, Tsutomu,Dairi, Tohru,Hoshino, Tsutomu
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p. 1016 - 1018
(2007/10/03)
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- Ionic liquids as reagents and solvents in conjunction with microwave heating: Rapid synthesis of alkyl halides from alcohols and nitriles from aryl halides
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We show that using ionic liquids as reagents in conjunction with microwave heating it is possible to prepare primary alkyl halides from the corresponding alcohols rapidly. Using ionic liquids as solvents in conjunction with microwave heating it is possible to prepare aryl nitriles from the corresponding aryl bromides or iodides. The scope and limitations of using microwave-promotion as a tool in these reactions is discussed.
- Leadbeater, Nicholas E.,Torenius, Hanna M.,Tye, Heather
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p. 2253 - 2258
(2007/10/03)
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- Compounds having protected hydroxy groups
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The present invention relates to compounds with protected hydroxy groups of formula (I) These compounds are precursors for organoleptic agents, such as fragrances, and masking agents and for antimicrobial agents. When activated, the compounds of formula (I) are cleaved and form one or more organoleptic and/or antimicrobial compounds.
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- Compounds having protected hydroxy groups
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The present invention relates to compounds with protected hydroxy groups of formula (I) These compounds are precursors for organoleptic agents, such as fragrances, and masking agents and for antimicrobial agents. When activated, the compounds of formula (I) are cleaved and form one or more organoleptic and/or antimicrobial compounds.
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- Semiochemicals of the scarabaeinae. VII: Identification and synthesis of ead-active constituents of abdominal sex attracting secretion of the male dung beetle, Kheper subaeneus
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Using gas chromatography with flame ionization detection (FID) and electroantennographic detection (EAD) in parallel, butanoic acid, skatole, and (E)-2,6-dimethyl-6-octen-2-ol were identified as constituents of the abdominal sex-attracting secretion of the male dung beetle, Kheper subaeneus, which reproducibly elicited EAD responses in male and female antennae. This is the first report of the occurrence of (E)-2,6-dimethyl-6-octen-2-ol as a natural product, for which the name (E)-subaeneol is proposed. In some experiments, a few other constituents of the secretion also gave reproducible responses in specific male and female antennae but did not elicit responses when the analyses were repeated with other antennae. The major volatile constituent of the secretion, identified as (S)-(+)-2,6-dimethyl-5-heptenoic acid, is one of these EAD-active compounds. Both this compound and (E)-2,6-dimethyl-6-octen-2-ol were synthesized from authentic starting materials for comparison with the natural products.
- Burger,Petersen,Weber,Munro
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p. 2527 - 2539
(2007/10/03)
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- Oxidation of sulfides to sulfoxides and sulfones with 30% hydrogen peroxide under organic solvent- and halogen-free conditions
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Aromatic and aliphatic sulfides are oxidized to sulfoxides or sulfones in high yield with 30% hydrogen peroxide under organic solvent- and halogen-free conditions. Dialkyl and alkyl aryl sulfides are cleanly oxidized to sulfoxides using aqueous hydrogen peroxide without catalysts. The best catalyst for the sulfone synthesis consists of sodium tungstate, phenylphosphonic acid, and methyltrioctylammonium hydrogensulfate. Co-existing primary or secondary alcohol or olefinic moieties are unaffected under such conditions.
- Sato, Kazuhiko,Hyodo, Mamoru,Aoki, Masao,Zheng, Xiao-Qi,Noyori, Ryoji
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p. 2469 - 2476
(2007/10/03)
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- Facile syntheses of [8,9-2H2]- and [8-2H]-digeranyl
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[8,9-2H2]- and [8-2H]-(2E,6E,10E,14E)-2,6,11,15-tetramethyl-2,6,10,14-hexadecatetraene (digeranyl) (1 and 2) have been synthesized from geraniol by the condensation of geranyl p-tolylsulfone and reductive desulfonylation in the key steps.
- Nakagawa, Osamu,Shimoda, Kei,Izumi, Shunsuke,Hirata, Toshifumi
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p. 1301 - 1309
(2007/10/03)
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- A novel method for the stereoselective formation of trans bicyclic ketones by way of oxidative radical cyclization
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The stereoselective formation of cyanohydrin 4 was achieved by radical cyclization-oxygen trapping reaction of 5 into an intramolecular acrylic nitrile moiety. The cyanohydrin was used for ring closure reaction with a tosylate, providing the bicyclic systems 1 and 2 with a trans ring fusion.
- Takahashi, Takashi,Tomida, Satoshi,Doi, Takayuki
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p. 644 - 646
(2007/10/03)
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- Esterification of carboxylic acid salts
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Mono- or polycarboxylic acid esters are prepared by reacting a salt of such carboxylic acid with an organic halocompound, e.g., a (cyclo)alkyl, (cyclo)alkenyl, aryl or aralkyl halide, in an aqueous reaction medium, in the presence of a catalytically effective amount of a phase transfer catalyst, for example an onium salt.
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- Alkylation of Enaminoketone with a Modified Carane Skeleton. Formation of Stable β-Diketone Monoimines
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Alkylation of a bicyclic enaminoketone, 1-[(1R,5R)-3-amino-6,6-dimethylbicyclo[3.1.0]hex-2-en-2-yl)]ethanone, with highly reactive alkyl halides (methyl iodide, benzyl halides, and allyl halides) in a two-phase system benzene-40% aqueous NaOH in the presence of benzyltriethylammonium chloride (BTEA) as phase-transfer catalyst results in formation of stable β-diketone monoimines, derivatives of the series of 1-[(1R,5R)-2-alkyl-3-imino-6,6-dimethylbicyclo[3.1.0]hex-2-yl]ethanone, in 53-81% yields.
- Tkachev,Popov
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p. 601 - 606
(2007/10/03)
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- Semiempirical AM1 Calculations on the Competing 1- and 4-Alkylation of 2-Methylbuta-1,3-diene with Primary Allylic Cations
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The strict regioselectivity of the attack of various carbenium ions on 2-methylbuta-1,3-diene at C-1 is not valid in the case of primary-tertiary allylic cations (such as 2-5) which also attack at C-4 (≈20%), a phenomenon which is rationalized by a cyclic HOMO-LUMO interaction of isoprene and allylic cations.
- Martin, Ivar,Muks, Elvi
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- Method for lowering cholesterol employing a phosphonomethylphosphinate squalene synthetase inhibitor
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A method is provided for inhibiting cholesterol biosynthesis by inhibiting de novo squalene production employing methylene phosphonoalkylphosphinate compounds.
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- Methods of using α-phosphonosulfonate squalene synthetase inhibitors including the treatment of atherosclerosis and hypercholesterolemia
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α-Phosphonosulfonate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula STR1 wherein R2 is OR5 or R5a ; R3 and R5 are independently H, alkyl, arylalkyl, aryl or cycloalkyl; R5a is H, alkyl, arylalkyl or aryl; R4 is H, alkyl, aryl, arylalkyl, or cycloalkyl;, Z is H, halogen, lower alkyl or lower alkenyl; and R1 is a lipophilic group which contains at least 7 carbons and is alkyl, alkenyl, alkynyl, mixed alkenyl-alkynyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, cycloheteroalkyl, cycloheteroalkylalkyl; as further defined above; including pharmaceutically acceptable salts and or prodrug esters of the phosphonic (phosphinic) and/or sulfonic acids.
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- Chromium(II)-Mediated Stereodivergent Additions of Allylic Phosphates and Halides to Aldehydes
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The addition of γ-disubstituted allylchromium(III) reagents to aldehydes proceeds in a stereodivergent manner, in contrast to the case of γ-monosubstituted allylchromium(III) species.The method allows the preparation of a variety of homoallylic alcohols bearing a quaternary center of defined relative configuration in the α-position.The preparation of both stereomeric homoallylic alcohols 13 is possible by using either of the two (E)- or (Z)-allylic precursors.The reaction has been extended to a γ-monosubstituted β-(trimethylsilyl)allylic system.The intermediate allylic chromium(III) reagents can be conveniently prepared from the corresponding phosphates (or chlorides) in DMPU or THF in the presence of catalytic amounts of LiI.
- Nowotny, Stefan,Tucker, Charles E.,Jubert, Carole,Knochel, Paul
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p. 2762 - 2772
(2007/10/02)
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- α-phosphonocarboxylate squalene synthetase inhibitors
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α- Phosphonocarboxylate compounds are provided which inhibit the enzyme squalene synthetase and thereby inhibit cholesterol biosynthesis. These compounds have the formula STR1 wherein R1 is a lipophilic group which contains at least 7 carbons and is substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl or optionally substituted aryl; Z is H, halogen, hydroxy, hydroxyalkyl or lower alkyl; R2 and R3 are independently H, metal ion or other pharmaceutically acceptable cation, or a prodrug ester; R4 is H, metal ion or other pharmaceutically acceptable cation, lower alkyl, lower alkenyl, arylalkyl, aryl or a prodrug ester.
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- Polyisoprene compounds and salts thereof
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There are given disclosures on a polyisoprene compound of the formula STR1 wherein Y is S, O, NH or STR2 l is an integer of 2-10, Z is a group of STR3 R1 and R2 are same or different and each means a hydrogen atom or an alkyl group having C1-4, m is an integer of 0 or 1, and n is an integer of 0, 1 or 2, a salt thereof, a process for the preparation of same, and use thereof.
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- Bisphosphonate squalene synthetase inhibitors and method
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Compounds which are inhibitors of cholesterol biosynthesis (by inhibiting de novo squalene biosynthesis), and thus are useful as hypocholesterolemic agents and antiatherosclerotic agents are provided which have the structure STR1 and analogs thereof, wherein R1, R2, R3 and R4 are the same or different and are H, lower alkyl, a metal ion or a prodrug ester; R5 is H, halogen or lower alkyl; Zq is substituted alkenyl, substituted alkynyl, mixed alkenyl-alkynyl or substituted phenylalkyl or, phenylalkenyl or phenylalkynyl, or alkyl, including all stereoisomers thereof. New methods for using such compounds to inhibit cholesterol biosynthesis are also provided.
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- SYNTHESIS OF ALKYL HALIDES UNDER NEUTRAL CONDITIONS
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Primary and secondary alcohols are efficiently converted to the corresponding alkyl halides under neutral conditions.
- Munyemana, Francois,Frisque-Hesbain, Anne-Marie,Devos, Alain,Ghosez, Leon
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p. 3077 - 3080
(2007/10/02)
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- The Cyclisation of Geraniol in Superacids
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The cyclisation of geraniol (1) in FSO3H-SO2 at -78 deg C to yield the iridoid ether 3β,4α,6aα-trimethyl-cis-perhydrocyclopentafuran was investigated.Decomposition of the ether in FSO3H at room temperature gave the 2-isopropyl-1,3-dimethylcyclopentenium ion, whose structure was confirmed independently.Synthesis of geraniol labelled with deuterium on the gem-dimethyl group and on the single methyl group established the positions of these mehtyls in the iridoid ether.Synthesis of 2-(1-hydroxy-2,2-dimethylcyclopentyl)propan-1-ol established that the ion derived from it did not lie on the reaction pathway.
- Carr, Graham,Dean, Christopher,Whittaker, David
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- INVESTIGATION OF ION-CATALYZED TELOMERIZATION. XXIV. THE COMPOSITION OF SESQUITERPENE CHLORIDES - THE DIADDUCTS OF ISOPRENE WITH ITS MONOHYDROCHLORIDES
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The isomeric composition of primary allylic sesquiterpene chlorides, i.e., the diadducts of the isoprene telomer with its monohydrochlorides, was interpreted by 13C NMR spectroscopy.The diadducts are formed predominantly by telomerization chain growth, and the chemical structure and composition are determined by the chemical structure of the taxogen.The possibility of increasing the yield with increase in the excess of the taxogen is suggested.
- Siirde, K. E.,Erm, A. Yu.,Muks, E. A.,Vyalimyae, T. K.,Krumm, L. L.,Leets, K. V.
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p. 832 - 836
(2007/10/02)
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