30515-28-7Relevant academic research and scientific papers
Employing in vitro metabolism to guide design of F-labelled PET probes of novel α-synuclein binding bifunctional compounds
Aigbogun, Omozojie P.,Allen, Kevin J. H,Krol, Ed S.,Lee, Jeremy S.,Nwabufo, Chukwunonso K.,Owens, Madeline N.,Phenix, Christopher P.
supporting information, p. 885 - 900 (2021/07/09)
A challenge in the development of novel 18F-labelled positron emission tomography (PET) imaging probes is identification of metabolically stable sites to incorporate the 18F radioisotope. Metabolic loss of 18F from PET probes in vivo can lead to misleading biodistribution data as displaced 18F can accumulate in various tissues. In this study we report on in vitro hepatic microsomal metabolism of novel caffeine containing bifunctional compounds (C8-6-I, C8-6-N, C8-6-C8) that can prevent in vitro aggregation of α-synuclein, which is associated with the pathophysiology of Parkinson’s disease. The metabolic profile obtained guided us to synthesize stable isotope 19F-labelled analogues in which the fluorine was introduced at the metabolically stable N7 of the caffeine moiety. An in vitro hepatic microsomal metabolism study of the 19F-labelled analogues resulted in similar metabolites to the unlabelled compounds and demonstrated that the fluorine was metabolically stable, suggesting that these analogues are appropriate PET imaging probes. This straightforward in vitro strategy is valuable for avoiding costly stability failures when designing radiolabelled compounds for PET imaging.
Illiberis ulmivora Graeser sex attractant and preparation method thereof
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, (2021/07/01)
The invention provides an Illiberis ulmivora Graeser sex attractant, which comprises cis-7-dodecenoic acid-2-butyl ester and cis-9-tetradecenoic acid-2-butyl ester. The invention also provides a preparation method of the Illiberis ulmivora Graeser sex attractant, which comprises the steps of reducing pimelic acid and azelaic acid into 7-hydroxyheptanoic acid through lithium aluminum hydride, brominating the 7-hydroxyheptanoic acid, performing acylating chlorination on the 7-hydroxyheptanoic acid and thionyl chloride, esterifying the 7-hydroxyheptanoic acid and the thionyl chloride with sec-butyl alcohol to form 7-bromoheptanoic acid-2-butanol ester and 9-bromononanoic acid-2-butanol ester, preparing corresponding phosphine salt from the 7-bromoheptanoic acid-2-butanol ester and the 9-bromononanoic acid-2-butanol ester and triphenylphosphine, and then carrying out wittig reaction with n-valeraldehyde to synthesize a target compound. According to the Illiberis ulmivora Graeser sex attractant and the preparation method thereof, raw materials are easy to obtain, operation is easy and convenient, the cost is low, the product yield is high, the technological process is short, synthesis reaction conditions are mild, no danger exists, the product is easy to separate, for the stereoisomerization problem, unstable phosphorus ylide reacts with fatty aldehyde, the product is mainly cis-olefin, the yield is 90% or above, the stable phosphorus ylide reacts with fatty aldehyde, and the product is mainly trans-olefin.
Total Syntheses of (R)-Strongylodiols C and D
Liu, Feipeng,Zhong, Jiangchun,Li, Shuoning,Li, Minyan,Wu, Lin,Wang, Qian,Mao, Jianyou,Liu, Shikuo,Zheng, Bing,Wang, Min,Bian, Qinghua
supporting information, p. 244 - 247 (2016/02/05)
The first total syntheses of two marine natural products, (R)-strongylodiols C and D, with 99% ee were achieved. The key steps of the strategy include the zipper reaction of an alkyne, the asymmetric alkynylation of an unsaturated aliphatic aldehyde catalyzed with Trost's ProPhenol ligand, and the Cadiot-Chodkiewicz cross-coupling reaction of a chiral propargylic alcohol with a bromoalkyne.
A marine natural product (R) - 24-methyl-twenty-five carbon -2, 4, 16- three alkyne -1,6-diol and its antimer synthesis method
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Paragraph 0013; 0055-0056, (2019/02/04)
The invention discloses a synthetic method for a marine natural product (R)-24-methyl-pentacosa-2,4,16-trialkynyl-1, 6-diol and enantiomer thereof, which belongs to the field of chemical synthesis. According to the invention, propargyl alcohol is used as a starting material, and a plurality of steps of reactions like coupling, transposition, oxidation, selective reduction, asymmetric alkynylation addition, esterification and hydrolysis are carried out to synthesize the marine natural product and enantiomer thereof; a key step is that trimethyl silicon-based acetylene and alkynal undergo asymmetric addition so as to produce a high-optical purity alkynol fragment in one step; and long-chain iodoalkane added in the process of synthesis is prepared through a series of simple reactions including bromination, oxidation, esterification, reduction and the like, so reaction route is greatly shortened. The synthesis of the natural product provided by the invention is reported for the first time; the synthetic method has the characteristics of simple steps, high total yield, good product stereoselectivity, etc.; and the optical purities of the products with two configurations are both greater than 99% ee.
A marine natural product (R, Z) - 24-methyl-twenty-five carbon -16-butene -2,4-diyne -1,6-diol and its antimer synthesis method
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Paragraph 0013; 0059-0060, (2020/05/06)
The invention relates to a synthetic method of a marine natural product namely (R, Z)-24-methyl-25-carbon-16-butylene-2,4-diyne-1,6-diol and an enantiomer thereof, and belongs to the field of chemical synthesis. The synthetic method comprises the following steps: firstly, preparing long chain alkyl iodide by using a series of simple reactions including bromination, oxidation, esterification, reduction and the like; and then, performing multiple steps of reactions including coupling, dislocation, oxidation, selective reduction, asymmetric alkynylation addition, esterification, hydrolysis and the like by taking propargyl alcohol and the long chain alkyl iodide as starting materials to synthesize the marine natural product namely (R, Z)-24-methyl-25-carbon-16-butylene-2,4-diyne-1,6-diol and the enantiomer thereof, wherein the key step is that trimethylsilylacetylene and alkynal are subjected to asymmetric addition reaction to generate alkynol segments with high optical purity by one step. The synthetic method provided by the invention reports the synthesis of the natural product of the type for the first time, and has the characteristics of simple and convenient steps, relatively high total yield, good product stereoselectivity and the like, and the optical purity of each of the two types of synthesized products is more than 99%ee.
Hydroxamic acid derivative and JHDM inhibitor
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Paragraph 0053, (2016/10/09)
PROBLEM TO BE SOLVED: To provide a compound capable of selectively inhibiting the function of JHDM, and a JHDM inhibitor. SOLUTION: This hydroxamic acid derivative expressed by formula (1a) [wherein, R1and R2are each independently alkyl which may have a branch; and (n) is an integer of ≥1] or general formula (1b) [wherein, ring X is a 3 to 8-membered saturated carbon ring; and (n) is an integer of ≥1], its pharmaceutically acceptable salt, hydrate, solvate or prodrug is provided. COPYRIGHT: (C)2011,JPOandINPIT
HDAC INHIBITING DERIVATIVES OF CAMPTOTHECIN
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Page/Page column 37, (2012/07/28)
The disclosure includes hydroxamic compounds of Formula I: (Formula I) wherein Z, L, R1, R2, and R3 are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.
Sequence-specific base pair mimics are efficient topoisomerase IB inhibitors
Vekhoff, Pierre,Duca, Maria,Guianvarc'h, Dominique,Benhida, Rachid,Arimondo, Paola B.
experimental part, p. 43 - 51 (2012/05/20)
Topoisomerase IB controls DNA topology by cleaving DNA transiently. This property is used by inhibitors, such as camptothecin, that stabilize, by inhibiting the religation step, the cleavage complex, in which the enzyme is covalently attached to the 3'-phosphate of the cleaved DNA strand. These drugs are used in clinics as antitumor agents. Because three-dimensional structural studies have shown that camptothecin derivatives act as base pair mimics and intercalate between two base pairs in the ternary DNA- topoisomerase-inhibitor complex, we hypothesized that base pairs mimics could act like campthotecin and inhibit the religation reaction after the formation of the topoisomerase I-DNA cleavage complex. We show here that three base pair mimics, nucleobases analogues of the aminophenyl-thiazole family, once targeted specifically to a DNA sequence were potent topoisomerase IB inhibitors. The targeting was achieved through covalent linkage to a sequencespecific DNA ligand, a triplex-forming oligonucleotide, and was necessary to position and keep the nucleobase analogue in the cleavage complex. In the absence of triplex formation, only a weak binding to the DNA and topoisomerase I-mediated DNA cleavage was observed. The three compounds were equally active once conjugated, implying that the intercalation of the nucleobase upon triplex formation is the essential feature for the inhibition activity.
Carbon-carbon bond fission on oxidation of primary alcohols to carboxylic acids
Bekish, Andrei V.
scheme or table, p. 3082 - 3085 (2012/07/28)
α-Carbon-carbon bond cleavage is shown to be a general side reaction accompanying the oxidation of unbranched primary alcohols to the corresponding carboxylic acids using HNO3, CrO3/H2SO 4/H2O/acetone, CrO3/CH3COOH, PDC/DMF, H5IO6/CrO3, KMnO4/H +, KMnO4/HO-, NiCl2/NaClO, TEMPO/PhI(OAc)2. Therefore, the product formed is always contaminated with a carboxylic acid containing one carbon atom less. Systems such as PhI(OAc)2/TEMPO or H5IO6/CrO 3/CH3CN reduce to a minimum the content of this impurity. Temperature, the order of reagent addition, and additives such as oxalic acid or cerium salts produce a profound effect on the formation of the undesirable impurity during the Jones oxidation of primary alcohols.
Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: Synthesis, biological activity, and computational evaluation
Botta, Cinzia B.,Cabri, Walter,Cini, Elena,De Cesare, Lucia,Fattorusso, Caterina,Giannini, Giuseppe,Persico, Marco,Petrella, Antonello,Rondinelli, Francesca,Rodriquez, Manuela,Russo, Adele,Taddei, Maurizio
experimental part, p. 2165 - 2182 (2011/05/14)
Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select a potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds were evaluated for their in vitro inhibitory activity against the 11 human HDACs isoforms. After identification of a "hit" molecule, a programmed variation at the cap group and at the linker was carried out in order to increase HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed increased activity against a number of HDAC isoforms, even if their overall activity range is still far from the inhibition values reported for SAHA. Moreover, different from what was reported for their hydroxamic acid analogues the new α-oxime amide derivatives do not select between class I and class II HDACs; rather they target specific isoforms in each class. These somehow contradictory results were finally rationalized by a computational assisted SAR, which gave us the chance to understand how the oxime derivatives interact with the catalytic site and justify the observed activity profile.
