- Facile Hetero-Diels-Alder Reaction of α,β-Unsaturated Acyl Cyanides and Enol Ethers: Synthesis of 2-Alkoxy-3,4-dihydro-2H-Pyran-6-carbonitriles
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2-Ethoxy-3,4-dihydro-2H-pyran-6-carbonitriles are obtained in high yield by stereospecific endo-mode cycloadditions of α,β-unsaturated acyl cyanides and ethyl vinyl ether at room temperature.The nitrile group is converted to some other functionalities.
- John, Robert A.,Schmid, Vincent,Wyler, Hugo
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Read Online
- Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis
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A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.
- Lee, Hyo-Jun,Huang, Xiao,Sakaki, Shigeyoshi,Maruoka, Keiji
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supporting information
p. 848 - 855
(2021/02/09)
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- Synthesis of N-trifluoromethyl amides from carboxylic acids
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Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.
- Flavell, Robert R.,Liu, Jianbo,Parker, Matthew F. L.,Toste, F. Dean,Wang, Sinan,Wilson, David M.
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supporting information
p. 2245 - 2255
(2021/08/12)
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- The emodin succinyl ester compounds in the preparation of pharmaceutical use in fat
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The invention discloses emodin succinyl ester compounds in the preparation of the use of the drug in the blood, which belongs to the field of medical technology, the emodin succinyl ester compound of the structure shown in formula I (R is C1 - 5 Alkyl). The experiment mixed hyperlipidemia rats pharmacological experiment, confirms that the emodin succinyl ester compound is superior to the emodin, with hypolipidemic effects are prominent, good safety, administration is simple and convenient, cheap price of raw materials are easy, convenient transportation and storage advantages. The invention of the proposed emodin succinyl ester compound in the blood lipid-lowering medicine preparation field will have broad application prospects.
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Paragraph 0056; 0064; 0070
(2018/07/30)
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- Intermediate for standard auspicious Luo river (1R, 2S) - 2 - (2,3-difluorophenyl) method for the preparation of cyclopropylamines (by machine translation)
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The invention discloses a method for preparing ticagrelor midbody (1R,2S)-2-(2,3-difluorophenyl) cyclopropylamine, belonging to the technical fields of organic synthesis route design and preparation of raw material medicines and midbodies. The method comprises the following steps: performing alcoholysis on succinic anhydride, thereby obtaining mono-methyl succinate, performing acylating chlorination reaction on mono-methyl succinate, thereby obtaining a compound methyl 4-chloro-4-oxobutyrate, performing Fridel-Crafts reaction on methyl 4-chloro-4-oxobutyrate and o-difluorobenzene, thereby obtaining a compound methyl 4-ketone-4-(3,4-difluorophenyl) butyrate (IV), and further performing asymmetric reduction reaction, cyclization reaction and Hoffman degradation on the compound IV, thereby obtaining the compound (1R,2S)-2-(2,3-difluorophenyl) cyclopropylamine. Initial raw materials used in the method are low in cost and easy to obtain, the reaction condition is gentle, the operation is safe, simple and convenient, the environment pollution is small, and the key ticagrelor midbody prepared by using the method is simple and convenient in after treatment, and is beneficial to on-scale production.
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Paragraph 0038; 0040
(2017/03/23)
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- COMPOUND FOR PROMOTING APOPTOSIS OF CANCER CELLS AND A PHARMACEUTICAL COMPOSITION CONTAINING THE SAME AND USES THEREOF
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The present invention provides a compound of Formula (I) and a salt thereof, wherein, m is an integer of 2 to 7, and R is independently at least one selected from the group consisting of hydrogen and C1-C20 alkyl. The compound promotes apoptosis in cancer cell and inhibits its growth. The present invention also provides a pharmaceutical composition which comprises the compound of Formula (I), a salt thereof and a pharmaceutically acceptable carrier. The present invention further provides a method for production of the pharmaceutical composition used for treating cancer.
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Paragraph 0087
(2016/04/20)
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- Optimization of gefitinib analogues with potent anticancer activity
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The interactions of gefitinib (Iressa) in EGFR are hydrogen bonding and van der Waals forces through quinazoline and aniline rings. However the morpholino group of gefitinib is poorly ordered due to its weak electron density. A series of novel piperazino analogues of gefitinib where morpholino group substituted with various piperazino groups were designed and synthesized. Most of them indicated significant anti-cancer activities against human cancer cell lines. In particular, compounds 52-54 showed excellent potency against cancer cells. Convergent synthetic approach has been developed for the synthesis of gefitinib intermediate which can lead to gefitinib as well as numerous analogues.
- Yin, Kai-Hao,Hsieh, Yi-Han,Sulake, Rohidas S.,Wang, Su-Pei,Chao, Jui-I.,Chen, Chinpiao
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supporting information
p. 5247 - 5250
(2015/01/08)
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- HETEROCYCLIC COMPOUND
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The present invention relates to wherein each symbol is as defined in the specification. The compound of the present invention has a superior RBP4-lowering action, and is useful as a medicament for the prophylaxis or treatment of disease and condition mediated by increased RBP4.
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Page/Page column 84-85
(2010/07/08)
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- Succinylphosphonate esters are competitive inhibitors of MenD that show active-site discrimination between homologous α-ketoglutarate- decarboxylating enzymes
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MenD is a thiamin diphosphate-dependent enzyme catalyzing the first unique step in menaquinone biosynthesis in bacteria. We have synthesized acylphosphonate ester analogues of a-ketoglutarate, a substrate of MenD. These compounds are competitive inhibitors of MenD, with Ki values as low as 700 nM. Observed structure-activity relationships are in notable contrast to those reported previously for succinylphosphonate inhibition of the a-ketoglutarate dehydrogenase complex, despite the apparent homology of these enzymes, and the identical decarboxylation reactions catalyzed. Inhibiting menaquinone biosynthesis is a proposed approach to inhibiting Mycobacterium tuberculosis growth. These inhibitors showed no significant inhibition of M. tuberculosis growth in vitro under aerobic and hypoxic conditions but give new information about the binding characteristics of the MenD active site. Site-directed mutation of Ser391 to alanine had only a minor effect on catalysis, but even the conservative mutation of Arg395 to lysine had a significant effect on the catalytic processing of isochorismate.
- Fang, Maohai,Daniel Toogood,Macova, Andrea,Ho, Karen,Franzblau, Scott G.,McNeil, Michael R.,Sanders, David A.R.,Palmer, David R.J.
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body text
p. 2672 - 2679
(2011/03/19)
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- Synthesis and characterization of naphth-annelated thiophene analogs
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Synthesis of symmetrical and unsymmetrical naphth-annelated thienyl heterocycles has been achieved via thionation of hydroxyketones/diketones using Lawesson's reagent. Photophysical studies of 1,3-disubstituted naphtho[c]thiophene analogs are presented. Electro-oxidative behavior of these naphtha-annelated thiophenes are investigated using cyclic voltammeter.
- Clement, J. Arul,Mohanakrishnan, Arasambattu K.
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experimental part
p. 2340 - 2350
(2010/06/12)
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- Synthesis and anti-cancer activity of C-ring-functionalized prodigiosin analogues
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Prodigiosin is the parent member of the 4-methoxypyrrolyldipyrromethene family of natural products and is known for its anti-cancer activity. A new series of analogues was synthesized, incorporating pendent functional esters and β-carbonyl substituents on the C-ring. The β-carbonyl group allowed for the facile isolation of the prodigiosenes, and the pendent esters allow for further derivatization. The novel prodigiosenes generally retain the anti-cancer activity of prodigiosin in 60 human cell lines derived from nine cancer cell types, with neither the conjugated /3-carbonyl group, as either ketone or ester, nor the pendent ester significantly reducing the anti-cancer activity of the core skeleton.
- Regourd, Jasmine,Ali, Adeeb Al-Sheikh,Thompson, Alison
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p. 1528 - 1536
(2008/02/02)
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- SUBSTITUTED CYCLOHEXYL-1,4-DIAMINE DERIVATIVES WITH A CHAIN EXTENSION
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The invention relates to substituted cyclohexyl-1,4-diamine derivatives, to a method for their production, to medicaments containing said compounds and to the use of substituted cyclohexyl-1,4-diamine derivatives for producing medicaments.
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Page/Page column 25
(2008/06/13)
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- A New Class of Linear Tetrapyrroles: Acetylenic 10,10a-Didehydro-10a-homobilirubins
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Novel bilirubin analogues with dipyrrinones conjoined to an acetylene rather than a methylene group were synthesized and examined spectroscopically. Despite the increased separation of the dipyrrinones forced by replacing a -CH2- by a -C≡C- unit, molecular dynamics calculations show that, like bilirubin, they may still engage in intramolecular hydrogen bonding to carboxylic acid groups when the propionic acid chains are slightly lengthened, e.g., butanoic acids. Unlike bilirubin, however, which is bent in the middle and has a ridge-tile shape, the acetylene orients the attached dipyrrinones along a linear path, and intramolecular hydrogen bonding preserves a twisted linear molecular shape. The extended planes of the dipyrrinones intersect along the -C≡C- axis at an angle of 136° for the conformation stabilized by intramolecular hydrogen bonding in the bis-butyric acid rubin (lb). With shorter acid chains (propionic), only one CO2H can engage an opposing dipyrrinone in intramolecular hydrogen bonding, and in this energy-minimum conformation of the linear pigment 1a, the intersection of the extended planes of the dipyrrinones has an angle of 171°. Spectroscopic evidence for such linearized and twisted structures was found in the pigments' NMR spectral data and their exciton UV-vis and induced circular dichroism spectra.
- Tu, Bin,Ghosh, Brahmananda,Lightner, David A.
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p. 8950 - 8963
(2007/10/03)
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- A combination of Friedel-Crafts and Lawesson reactions to 5-substituted 2,2′-bithiophenes
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γ-Keto esters (2) derivatives of thiophene were obtained from hemisuccinic esters and transformed to the corresponding amides (4). Lawesson's treatment of 2 and 4 gave the corresponding bithiophenes (5) with alkoxy or amino substituents.
- Raposo, M. Manuela M.,Kirsch
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p. 1487 - 1498
(2007/10/03)
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- Synthesis and investigation of N4-substituted cytarabine derivatives as prodrugs.
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Esters of Cytarabine-N4-carboxylates 2a-i and succinamates 3a-f were synthesized as prodrugs of cytarabine (Ara-C) with the aim of developing improved derivatives for oral or parentral administration. At pH 2 series 2 showed relative higher stability than 3, while both series of esters revealed matched stability at pH 7. All esters were susceptible to enzymatic hydrolysis by rat plasma and liver homogenate with half lives ranged from 0.14 h to 12 d, and showed improved stability against cytidine deaminase. A parabolic relation was shown between Kobs of enzymatic hydrolysis and Vw. All compounds are more lipophilic than the parent drug, Ara-C.
- Fadl,Hasegawa,Youssef,Farag,Omar,Kawaguchi
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p. 382 - 387
(2007/10/02)
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- Phyllanthoside-Phyllanthostatin Synthetic Studies. 7. Total Synthesis of (+)-Phyllanthocin and (+)-Phyllanthocindiol
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A stereochemically linear total synthesis of (+)-phyllanthocin (5a), the aglycon methyl ester of the antineoplastic glycoside (+)-phyllanthoside (1), is described. The synthesis proceeds in 23 steps (4.5% overall yield) and affords (+)-phyllanthocin in high enantiomeric purity. The central features of the strategy include: (a) construction of aldehyde 8 via a stereoselective, intramolecular ene reaction; (b) elaboration of the spiroketal unit by a two-step tactic involving addition of a functionalized dihydropyran anion (i.e., 9) to 8, followed by a highly stereoselective spiroketalization; and (c) chemo- and stereoselective methylenation of the C(7) carbonyl group. In addition, a second-generation approach is presented, wherein an augmented spiroketalization maneuver not only establishes the C(8) spirocenter but also permits the regio- and stereocontrolled introduction of the C(11) methyl group. The latter sequence furnishes (+)-phyllanthocin in 21 steps (5.6% overall yield). Finally, the advanced phyllanthocin intermediate (+)-49 is converted in five steps (42% overall yield) to (+)-phyllanthocindiol (5b), the aglycon of phyllanthostatin 3.
- Smith III, Amos B.,Fukui, Mineo,Vaccaro, Henry A.,Empfield, James R.
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p. 2071 - 2092
(2007/10/02)
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