- Illiberis ulmivora Graeser sex attractant and preparation method thereof
-
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.
- -
-
-
- Employing in vitro metabolism to guide design of F-labelled PET probes of novel α-synuclein binding bifunctional compounds
-
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.
- 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)
-
- Total Syntheses of (R)-Strongylodiols C and D
-
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.
- 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)
-
- A marine natural product (R) - 24-methyl-twenty-five carbon -2, 4, 16- three alkyne -1,6-diol and its antimer synthesis method
-
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.
- -
-
Paragraph 0013; 0055-0056
(2019/02/04)
-
- A marine natural product (R, Z) - 24-methyl-twenty-five carbon -16-butene -2,4-diyne -1,6-diol and its antimer synthesis method
-
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.
- -
-
Paragraph 0013; 0059-0060
(2020/05/06)
-
- Hydroxamic acid derivative and JHDM inhibitor
-
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
- -
-
Paragraph 0053
(2016/10/09)
-
- Carbon-carbon bond fission on oxidation of primary alcohols to carboxylic acids
-
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.
- Bekish, Andrei V.
-
scheme or table
p. 3082 - 3085
(2012/07/28)
-
- HDAC INHIBITING DERIVATIVES OF CAMPTOTHECIN
-
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.
- -
-
Page/Page column 37
(2012/07/28)
-
- Sequence-specific base pair mimics are efficient topoisomerase IB inhibitors
-
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.
- Vekhoff, Pierre,Duca, Maria,Guianvarc'h, Dominique,Benhida, Rachid,Arimondo, Paola B.
-
experimental part
p. 43 - 51
(2012/05/20)
-
- Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: Synthesis, biological activity, and computational evaluation
-
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.
- 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)
-
- Fluoroalkene modification of mercaptoacetamide-based histone deacetylase inhibitors
-
Inhibitors of histone deacetylases (HDAC) are emerging as a promising class of anti-cancer agents. The mercaptoacetoamide-based inhibitors are reported to be less toxic than hydroxamate and are worthy of further consideration. Therefore, we have designed a series of analogs as potential inhibitors of HDACs, in which the mercaptoacetamide group was replaced by (mercaptomethyl)fluoroalkene, and their HDAC inhibitory activity was evaluated. Subnanomolar inhibition was observed for all synthetic compounds.
- Osada, Satoshi,Sano, Satoshi,Ueyama, Mariko,Chuman, Yoshiro,Kodama, Hiroaki,Sakaguchi, Kazuyasu
-
experimental part
p. 605 - 611
(2010/05/02)
-
- Binding of coenzyme B induces a major conformational change in the active site of methyl-coenzyme M reductase
-
Methyl-coenzyme M reductase (MCR) is the key enzyme in methane formation by methanogenic Archaea. It converts the thioether methyl-coenzyme M and the thiol coenzyme B into methane and the heterodisulfide of coenzyme M and coenzyme B. The catalytic mechanism of MCR and the role of its prosthetic group, the nickel hydrocorphin coenzyme F430, is still disputed, and no intermediates have been observed so far by fast spectroscopic techniques when the enzyme was incubated with the natural substrates. In the presence of the competitive inhibitor coenzyme M instead of methyl-coenzyme M, addition of coenzyme B to the active Ni(I) state MCRred1 induces two new species called MCR red2a and MCRred2r which have been characterized by pulse EPR spectroscopy. Here we show that the two MCRred2 signals can also be induced by the S-methyl- and the S-trifluoromethyl analogs of coenzyme B. 19F-ENDOR data for MCRred2a and MCRred2r induced by S-CF3-coenzyme B show that, upon binding of the coenzyme B analog, the end of the 7-thioheptanoyl chain of coenzyme B moves closer to the nickel center of F430 by more than 2 A as compared to its position in both, the Ni(I) MCRred1 form and the X-ray structure of the inactive Ni(II) MCRox1-silent form. The finding that the protein is able to undergo a conformational change upon binding of the second substrate helps to explain the dramatic change in the coordination environment induced in the transition from MCRred1 to MCRred2 forms and opens the possibility that nickel coordination geometries other than square planar, tetragonal pyramidal, or elongated octahedral might occur in intermediates of the catalytic cycle.
- Ebner, Sieglinde,Jaun, Bernhard,Goenrich, Meike,Thauer, Rudolf K.,Harmer, Jeffrey
-
experimental part
p. 567 - 575
(2010/03/25)
-
- Design, synthesis, and biological activity of folate receptor-targeted prodrugs of thiolate histone deacetylase inhibitors
-
Aiming to develop selective anticancer drugs, we designed and synthesized three disulfides bearing a folic acid moiety as candidate folate receptor (FR)-targeted prodrugs of thiolate histone deacetylase inhibitors. Among them, compound 1 displayed growth-inhibitory activity toward folate receptor-positive MCF-7 breast cancer cells. The activity of 1 was significantly reduced by free folic acid, suggesting that cellular uptake of 1 is mediated by FR.
- Suzuki, Takayoshi,Hisakawa, Shinya,Itoh, Yukihiro,Suzuki, Nobuaki,Takahashi, Katsumasa,Kawahata, Masatoshi,Yamaguchi, Kentaro,Nakagawa, Hidehiko,Miyata, Naoki
-
p. 4208 - 4212
(2008/02/12)
-
- Novel inhibitors of human histone deacetylases: Design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates
-
To find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, a series of compounds modeled after suberoylanilide hydroxamic acid (SAHA) was designed and synthesized. In this series, compound 7, in which the hydroxamic acid of SAHA is replaced by a thiol, was found to be as potent as SAHA, and optimization of this series led to the identification of HDAC inhibitors more potent than SAHA. In cancer cell growth inhibition assay, S-isobutyryl derivative 51 showed strong activity, and its potency was comparable to that of SAHA. The cancer cell growth inhibitory activity was verified to be the result of histone hyperacetylation and subsequent induction of p21WAF1/CIP1 by Western blot analysis. Kinetical enzyme assay and molecular modeling suggest the thiol formed by enzymatic hydrolysis within the cell interacts with the zinc ion in the active site of HDACs.
- Suzuki, Takayoshi,Nagano, Yuki,Kouketsu, Akiyasu,Matsuura, Azusa,Maruyama, Sakiko,Kurotaki, Mineko,Nakagawa, Hidehiko,Miyata, Naoki
-
p. 1019 - 1032
(2007/10/03)
-
- Identification of a potent non-hydroxamate histone deacetylase inhibitor by mechanism-based drug design
-
In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, mercaptoacetamide 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling are also reported. In order to find novel non-hydroxamate histone deacetylase (HDAC) inhibitors, we synthesized several suberoylanilide hydroxamic acid (SAHA)-based compounds designed on the basis of the catalytic mechanism of HDACs. Among these compounds, 5b was found to be as potent as SAHA. Kinetic enzyme assays and molecular modeling suggested that the mercaptoacetamide moiety of 5b interacts with the zinc in the active site of HDACs and removes a water molecule from the reactive site of the deacetylation.
- Suzuki, Takayoshi,Matsuura, Azusa,Kouketsu, Akiyasu,Nakagawa, Hidehiko,Miyata, Naoki
-
p. 331 - 335
(2007/10/03)
-
- Design and synthesis of non-hydroxamate histone deacetylase inhibitors: Identification of a selective histone acetylating agent
-
A series of suberoylanilide hydroxamic acid (SAHA)-based non-hydroxamates was designed, synthesized, and evaluated for their histone deacetylase (HDAC) inhibitory activity. Among these, methyl sulfoxide 15 inhibited HDACs in enzyme assays and caused hyperacetylation of histone H4 while not inducing the accumulation of acetylated α-tubulin in HCT116 cells.
- Suzuki, Takayoshi,Matsuura, Azusa,Kouketsu, Akiyasu,Hisakawa, Shinya,Nakagawa, Hidehiko,Miyata, Naoki
-
p. 4332 - 4342
(2007/10/03)
-
- Anilide compounds, including use thereof in ACAT inhibitition
-
The invention provides novel anilide compounds and pharmaceutical compositions comprising them. The invention relates to compounds of a formula: where Ar is an optionally-substituted aryl group; R4and R5are the same or different, and each is a hydrogen atom, a lower alkyl group, or a lower alkoxy group; and R4and R5may together form a lower alkylene group of which one or more methylene moieties may optionally be substituted by oxygen and/or sulfur atoms; X is —NH—, or oxygen or sulfur atom; Y is —NH—, an oxygen or sulfur atom, or a sulfoxide or sulfone group; Z is a single bond, or —NH6—; R6represents a hydrogen atom or a lower alkylene group; and n is an integer of from 0 to 15; and their salts and solvates. The compounds of the invention are useful as pharmaceutical compositions, especially as acyl coenzyme A cholesterol acyltransferase (ACAT) inhibitors.
- -
-
-
- Identification and total synthesis of novel fatty acids from the siphonarid limpet Siphonaria denticulata
-
The novel fatty acids 17-methyl-6(Z)-octadecenoic acid and 17-methyl-7(Z)-octadecenoic acid were identified for the first time in nature in the mollusk Siphonaria denticulata from Queensland, Australia. The principal fatty acids in the limpet were hexadecanoic acid, octadecanoic acid, and (Z)-9-octadecenoic acid, while the most interesting series of monounsaturated fatty acids was a family of five nonadecenoic acids with double bonds at either Δ7, Δ9, Δ12, or Δ13. The novel compounds were characterized using a combination of GC-MS and chemical transformations, such as dimethyl disulfide derivatization. The first total syntheses for the two novel methyl-branched nonadecenoic acids are also described, and these were accomplished in four to five steps and in high yields.
- Carballeira,Cruz,Hill,De Voss,Garson
-
p. 1426 - 1429
(2007/10/03)
-
- Endothelin antagonist
-
An endothelin antagonist comprising as the active ingredient a prostanoic acid derivative wherein the α-chain has eight or more skeletal carbon atoms.
- -
-
-
- Synthesis of saturated fatty acids 11C (13C)-labelled in the ω-methyl position
-
A method for the preparation of saturated fatty acids 11C (13C)-labelled in the ω-methyl position is described. A highly reactive zerovalent copper complex was prepared from lithium naphtalenide reduced lithium(2-thienyl)iodocuprate. The labelling precursors were obtained by addition of tert-butyl ω-iodocarboxylates to the organocuprate and these were reacted with [11C]methyl iodide to form 11C-labelled, protected intermediates. The tert-butyl ester protecting group was rapidly removed with trifluoroacetic acid, affording fatty acids 11C-labelled in the ω-methyl position. A solid phase extraction method was developed and preceded final HPLC purification. In a typical run starting with 2.75 GBq of [11C]methyl iodide, 375 MBq (66%) [16-11C]palmitic acid was obtained within 46 min from the end of radionuclide production.
- Neu, Henrik,Kihlberg, Tor,Langstroem, Bengt
-
p. 509 - 524
(2007/10/03)
-
- Treatment of inflammation with 15-keto-prostaglandin compounds
-
A method of treatment of inflammatory diseases which comprises administering, to a subject in need of such treatment, an anti-inflammatorily effective amount of a 15-keto-prostaglandin compound.
- -
-
-
- Promotion of wound-healing with 15-keto-prostaglandin compounds
-
A method for promoting healing of wound which comprises administering, to a subject in need of such treatment, a wound-healingly effective amount of a 15-ketoprostaglandin compound.
- -
-
-
- Treatment of cataract with 15-keto-prostaglandin compounds
-
A compound for treatment of a cataract which is a 15-ketoprostaglandin compound.
- -
-
-