- Novel synthetic approach to alfaprostol key intermediates via Stille coupling with an alkyne
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Novel intermediates based on the Corey skeleton for preparation of the ω-chain of non-halogenated unnatural prostaglandin analogues containing a triple bond at position 13–14 (PG numbering) were synthesized. The utilization of a novel synthetic approach towards a new tin intermediate, and subsequent Stille coupling opens up new possibilities for preparing these important pharmaceutical intermediates.
- Monteiro, Sara,Imramovsky, Ale?,Pauk, Karel,Pavlík, Jan
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Read Online
- Remote Regioselective Radical C-H Functionalization of Unactivated C-H Bonds in Amides: The Synthesis of gem-Difluoroalkenes
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The site-selective functionalization of unactivated aliphatic amines is an attractive and challenging synthetic approach. We herein report a general strategy for the remote site-selective functionalization of unactivated C(sp3)-H bonds in amides by photogenerated amidyl radicals to form gem-difluoroalkenes with trifluoromethyl-substituted alkenes. The site selectivity is controlled by a 1,5-hydrogen atom transfer (HAT) process of the amide. This photocatalyzed transformation shows both chemo- and site-selectivity, facilitating the formation of a secondary, tertiary, or quaternary carbon center.
- Hu, Qu-Ping,Cheng, Jing,Wang, Ying,Shi, Jie,Wang, Bi-Qin,Hu, Ping,Zhao, Ke-Qing,Pan, Fei
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supporting information
p. 4457 - 4462
(2021/05/26)
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- Remote Directed Isocyanation of Unactivated C(sp3)-H Bonds: Forging Seven-Membered Cyclic Ureas Enabled by Copper Catalysis
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Reported herein is an unprecedented copper-catalyzed site-selective ?-C(sp3)-H bonds activation of aliphatic sulfonamides for constructing the synthetically useful seven-membered N-heterocycles. A key to success is the use of in-situ-formed amide radicals, to activate the inert C(sp3)-H bond, and inexpensive TMSNCO, as a coupling reagent under mild conditions. To the best of our knowledge, this represents the first use of alkylamine derivatives as a five-membered synthon to prepare a seven-membered N-heterocycles.
- Zhang, Hongwei,Tian, Peiyuan,Ma, Lishuang,Zhou, Yulu,Jiang, Cuiyu,Lin, Xufeng,Xiao, Xiao
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supporting information
p. 997 - 1002
(2020/02/15)
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- Decarboxylative Borylation of mCPBA-Activated Aliphatic Acids
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A decarboxylative borylation of aliphatic acids for the synthesis of a variety of alkylboronates has been developed by mixing m-chloroperoxybenzoic acid (mCPBA)-activated fatty acids with bis(catecholato)diboron in N,N-dimethylformamide (DMF) at room temperature. A radical chain process is involved in the reaction which initiates from the B-B bond homolysis followed by the radical transfer from the boron atom to the carbon atom with subsequent decarboxylation and borylation.
- Wei, Dian,Liu, Tu-Ming,Zhou, Bo,Han, Bing
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supporting information
p. 234 - 238
(2020/01/02)
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- CARBONIC ANHYDRASE INHIBITORS AND ANTIBIOTICS AGAINST MULTIDRUG RESISTANT BACTERIA
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The invention described herein generally relates to novel therapeutic compounds, and in particular to carbonic anhydrase inhibitors as a narrow spectrum antibiotics against drug resistant bacteria and methods for treating those infection diseases in mammals using the described carbonic anhydrase inhibitors or a pharmaceutical formulation thereof.
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Paragraph 0088
(2020/07/14)
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- PHARMACEUTICAL COMPOUNDS AND THEIR USE AS INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 19 (USP19)
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Provided are USP19 inhibitors, methods of treating obesity, metabolic syndrome and/or diabetes using the USP19 inhibitor compounds, as well as those compounds for use in methods of treating obesity, metabolic syndrome and/or diabetes. Also provided are methods of treating muscular atrophy, for example cachexia or sarcopenia with USP19 inhibitor compounds, plus those compounds for use in methods of treating muscular atrophy.
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Page/Page column 93
(2020/07/04)
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- Optimization of Acetazolamide-Based Scaffold as Potent Inhibitors of Vancomycin-Resistant Enterococcus
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Vancomycin-resistant enterococci (VRE) are the second leading cause of hospital-acquired infections (HAIs) attributed to a drug-resistant bacterium in the United States, and resistance to the frontline treatments is well documented. To combat VRE, we have repurposed the FDA-approved carbonic anhydrase drug acetazolamide to design potent antienterococcal agents. Through structure-activity relationship optimization we have arrived at two leads possessing improved potency against clinical VRE strains from MIC = 2 μg/mL (acetazolamide) to MIC = 0.007 μg/mL (22) and 1 μg/mL (26). Physicochemical properties were modified to design leads that have either high oral bioavailability to treat systemic infections or low intestinal permeability to treat VRE infections in the gastrointestinal tract. Our data suggest the intracellular targets for the molecules are putative α-carbonic and γ-carbonic anhydrases, and homology modeling and molecular dynamics simulations were performed. Together, this study presents potential anti-VRE therapeutic options to provide alternatives for problematic VRE infections.
- Kaur, Jatinder,Cao, Xufeng,Abutaleb, Nader S.,Elkashif, Ahmed,Graboski, Amanda L.,Krabill, Aaron D.,Abdelkhalek, Ahmed Hassan,An, Weiwei,Bhardwaj, Atul,Seleem, Mohamed N.,Flaherty, Daniel P.
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p. 9540 - 9562
(2020/10/19)
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- BIM-46174 fragments as potential ligands of G proteins
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The 5,6,7,8-Tetrahydroimidazo[1,2-A]pyrazine derivative BIM-46174 has received attention as Gαq inhibitor. We conducted structural reductions to monocyclic and bicyclic substructures to explore the chemical space of BIM fragments and to gain insights into the pharmacophore of BIM-Type Gαq inhibitors. Two piperazin-2-one-containing fragments and a small library of bicyclic lactams featuring fused pyrazine and diazepine rings were synthesized and evaluated. The results of a second messenger-based cellular assay indicate that the entire BIM structure is required for efficient Gαq inhibition.
- Küppers, Jim,Benkel, Tobias,Annala, Suvi,Schnakenburg, Gregor,Kostenis, Evi,Gütschow, Michael
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supporting information
p. 1838 - 1843
(2019/11/02)
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- Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding
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Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.
- Thinnes, Cyrille C.,Lohans, Christopher T.,Abboud, Martine I.,Yeh, Tzu-Lan,Tumber, Anthony,Nowak, Rados?aw P.,Attwood, Martin,Cockman, Matthew E.,Oppermann, Udo,Loenarz, Christoph,Schofield, Christopher J.
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supporting information
p. 2019 - 2024
(2019/01/11)
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- Copper-Catalyzed Amide Radical-Directed Cyanation of Unactivated Csp3-H Bonds
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A method for site-selective intermolecular δ/?-Csp3-H cyanation of aliphatic sulfonamides is developed using TsCN as the cyanating reagent, catalyzed by a Cu(I)/phenanthroline complex. The mild, expeditious, and modular protocol allows efficient remote Csp3-H cyanation with good functional group tolerance and high regioselectivity. Mechanistic studies indicate that the reaction might proceed through a Cu(I)-mediated N-F bond cleavage to generate an amidyl radical, 1,5-HAT, and cyano group transfer of the resulting carbon radical with TsCN.
- Zhang, Hongwei,Zhou, Yulu,Tian, Peiyuan,Jiang, Cuiyu
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supporting information
(2019/03/19)
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- Synthetic Utility of N-Benzoyloxyamides as an Alternative Precursor of Acylnitrenoids for γ-Lactam Formation
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Described herein is the development of a new entry of acylnitrenoid precursors for γ-lactam synthesis via an intramolecular C-H amidation reaction. Upon Ir catalysis, N-benzoyloxyamides serve as efficient substrates to afford 5-membered amides. Mechanistic studies revealed that the generation of a putative Ir-carbonylnitrenoid via N-O bond cleavage is facilitated by the chelation of countercations. This protocol offers a convenient and step-economic route to γ-lactams starting from the corresponding carboxylic acids.
- Huh, Soohee,Hong, Seung Youn,Chang, Sukbok
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supporting information
p. 2808 - 2812
(2019/04/17)
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- Fungicidal Properties of Some Novel Trifluoromethylphenyl Amides
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Trifluoromethylphenyl amides (TFMPAs) were designed and synthesized as potential pesticides. Thirty-three structures were evaluated for fungicidal activity against three Colletotrichum species using direct bioautography assays. Active compounds were subsequently tested against C. fragariae, C. gloeosporioides, C. acutatum, Phomopsis obscurans, P. viticola, Botrytis cinerea and Fusarium oxysporum. The study identified 2-chloro-N-[2,6-dichloro-4-(trifluoromethyl)phenyl]acetamide (7a) as showing the strongest antifungal activity, and the broadest activity spectrum in this set against Colletotrichum acutatum (at 48 and 72 h) and Phomopsis viticola (at 144 h). The presence of triethylamine in its complex with N-[2,6-dichloro-4-(trifluoromethyl)phenyl]-2,2,3,3,3-pentafluoropropanamide (7b′) played an important role in the bioactivity, and depending on the concentration or fungal species it showed higher or lower activity than the parent amide. X-Ray crystallography has shown that the complex (7b′) is an ion pair, (C10H2Cl2F8NO)? (C6H16N)+, where a proton is transferred from the amide nitrogen to the triethylamine nitrogen and then connected by hydrogen bonding to the acyl oxygen (N?H 0.893 ?; H???O 1.850 ?; N???O 2.711 ?; N?H???O 161.2(13)°). Although none of these compounds were better than standards, this work revealed some potential lead structures for further development of active novel compounds.
- Tsikolia, Maia,Bernier, Ulrich R.,Wedge, David E.,Tabanca, Nurhayat,Abboud, Khalil A.,Linthicum, Kenneth J.
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- 4-HYDROXYPIPERIDINE DERIVATIVES AND THEIR USE AS INHIBITORS OF UBIQUITIN SPECIFIC PROTEASE 19 (USP19)
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Inhibitors of ubiquitin specific protease 19 (USP19) of Formula (I) are provided, together with pharmaceutical compositions comprising said inhibitors, and methods of use thereof. The compounds can be used in in the treatment of muscular atrophy, obesity, insulin resistance or type II diabetes or in reducing the loss of muscle mass.
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Page/Page column 74
(2019/08/26)
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- Non- C2-Symmetric Chiral-at-Ruthenium Catalyst for Highly Efficient Enantioselective Intramolecular C(sp3)-H Amidation
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A new class of chiral ruthenium catalysts is introduced in which ruthenium is cyclometalated by two 7-methyl-1,7-phenanthrolinium heterocycles, resulting in chelating pyridylidene remote N-heterocyclic carbene ligands (rNHCs). The overall chirality results from a stereogenic metal center featuring either a or Δabsolute configuration. This work features the importance of the relative metal-centered stereochemistry. Only the non-C2-symmetric chiral-at-ruthenium complexes display unprecedented catalytic activity for the intramolecular C(sp3)-H amidation of 1,4,2-dioxazol-5-ones to provide chiral -lactams with up to 99:1 er and catalyst loadings down to 0.005 mol % (up to 11 ?200 TON), while the C2-symmetric diastereomer favors an undesired Curtius-type rearrangement. DFT calculations elucidate the origins of the superior C-H amidation reactivity displayed by the non-C2-symmetric catalysts compared to related C2-symmetric counterparts.
- Zhou, Zijun,Chen, Shuming,Hong, Yubiao,Winterling, Erik,Tan, Yuqi,Hemming, Marcel,Harms, Klaus,Houk,Meggers, Eric
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supporting information
p. 19048 - 19057
(2019/12/04)
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- PHARMACEUTICAL COMPOUNDS
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The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.
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Page/Page column 70; 71
(2018/02/28)
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- Primary, Secondary, and Tertiary γ-C(sp3)-H Vinylation of Amides via Organic Photoredox-Catalyzed Hydrogen Atom Transfer
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An efficient strategy for primary, secondary and tertiary aliphatic γ-C(sp3)-H vinylation of amides with alkenylboronic acids is reported. These reactions are catalyzed by visible-light organic photoredox agents. Regioselective γ-C(sp3)-H vinylation of amides is controlled by a 1,5-hydrogen atom transfer of an amidyl radical generated in situ.
- Chen, Hui,Guo, Liangliang,Yu, Shouyun
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supporting information
p. 6255 - 6259
(2018/10/05)
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- Photoinduced, Copper-Catalyzed Decarboxylative C-N Coupling to Generate Protected Amines: An Alternative to the Curtius Rearrangement
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The Curtius rearrangement is a classic, powerful method for converting carboxylic acids into protected amines, but its widespread use is impeded by safety issues (the need to handle azides). We have developed an alternative to the Curtius rearrangement that employs a copper catalyst in combination with blue-LED irradiation to achieve the decarboxylative coupling of aliphatic carboxylic acid derivatives (specifically, readily available N-hydroxyphthalimide esters) to afford protected amines under mild conditions. This C-N bond-forming process is compatible with a wide array of functional groups, including an alcohol, aldehyde, epoxide, indole, nitroalkane, and sulfide. Control reactions and mechanistic studies are consistent with the hypothesis that copper species are engaged in both the photochemistry and the key bond-forming step, which occurs through out-of-cage coupling of an alkyl radical.
- Zhao, Wei,Wurz, Ryan P.,Peters, Jonas C.,Fu, Gregory C.
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supporting information
p. 12153 - 12156
(2017/09/12)
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- Directed γ-C(sp3)-H Alkylation of Carboxylic Acid Derivatives through Visible Light Photoredox Catalysis
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Visible light photoredox catalysis enables direct γ- C(sp3)-H alkylation of saturated aliphatic carbonyl compounds. Electron-deficient alkenes are used as the coupling partners in this reaction. Distinguished site selectivity is controlled by the predominant 1,5-hydrogen atom transfer of an amidyl radical generated in situ.
- Chen, Dian-Feng,Chu, John C. K.,Rovis, Tomislav
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supporting information
p. 14897 - 14900
(2017/10/31)
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- γ,δ,ε-C(sp3)-H Functionalization through Directed Radical H-Abstraction
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Aliphatic amides are selectively functionalized at the γ- and δ-positions through directed radical 1,5 and 1,6 H-abstractions, respectively. The initially formed γ- or δ-lactams are intercepted by N-iodosuccinimide and trimethylsilyl azide, leading to double and triple C-H functionalizations at the γ-, δ-, and ε-positions. This new reactivity is exploited to convert alkyls into amino alcohols and allylic amines.
- Liu, Tao,Mei, Tian-Sheng,Yu, Jin-Quan
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supporting information
p. 5871 - 5874
(2015/05/27)
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- Benzothiazinones: A novel class of adenosine receptor antagonists structurally unrelated to xanthine and adenine derivatives
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2-(Acyl)amino-4H-3,1-benzothiazin-4-ones and related thienothiazinones were identified as structurally novel antagonists at adenosine receptors (ARs). 6-Methyl-2-benzoylamino-4H-3,1-benzothiazin-4-one (10d) was found to be a balanced AR antagonist with affinity for all human (h) subtypes (Ki hA1 65.6 nM; hA2A 120 nM; hA2B 360 nM; hA 3 30.4 nM), while in rat (r), 10d was a highly potent A 1-selective antagonist (rA1 7.7 nM; rA2A 546 nM; rA2B 679 nM, rA3 >10000 nM). 2-(4- Methylbenzoylamino)-4H-3,1-benzothiazin-4-one (10g) was found to be a potent antagonist at human A2A (68.8 nM) and A3 ARs (23.0 nM) with high selectivity versus the other human AR subtypes. In contrast to A 1 and A3 ARs, A2A and A2B ARs tolerated bulky 2-acyl substituents. tert-Butyl (4-oxo-4H-3,1-benzothiazin-2- ylcarbamoyl)benzylcarbamate (15g, Ki hA2B 186 nM; hA 2A 603 nM) and 4-(4-benzylpiperazine-1-carbonyl)-N-(4-oxo-4H-3,1- benzothiazin-2-yl)benzamide (15k, hA2A 69.5 nM; hA2B 178 nM) were highly selective versus the other AR subtypes. 2-Acylamino-3,1- benzothiazin-4-ones represent novel scaffolds suitable for the development of potent and selective AR antagonists for each of the four receptor subtypes.
- Gütschow, Michael,Schlenk, Miriam,G?b, Jürgen,Paskaleva, Minka,Alnouri, Mohamad Wessam,Scolari, Silvia,Iqbal, Jamshed,Müller, Christa E.
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supporting information; experimental part
p. 3331 - 3341
(2012/06/04)
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- Renin Inhibitors
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Disclosed are compounds having the formula (I): wherein the R1, R2, R3, X, Y, A, L, and G are defined herein. These compounds bind to aspartic proteases to inhibit their activity and are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also disclosed are methods of use of the compounds of Formula I for ameliorating or treating aspartic protease related disorders in a subject in need thereof.
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Page/Page column 63
(2010/12/29)
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- 2,4,5-TRISUBSTITUTED THIAZOLE COMPOUNDS,PREPARATION METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICAL USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 43
(2009/04/23)
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- TRISUBSTITUTED THIAZOLE COMPOUNDS, PREPARATIONS METHODS, PHARMACEUTICAL COMPOSITIONS AND MEDICALS USES THEREOF
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The present invention relates to 2,4,5-trisubstituted thiazole compounds of formula (I) or all possible isomers, prodrugs, pharmaceutically acceptable salts, solvates or hydrates thereof for the inhibition of plasma PLTP activity and/or plasma CETP activity, wherein the substituents are as defined in the specification; a process for the preparation of the compounds of formula (I); a pharmaceutical composition comprising the compound of formula (I) and its use for the preparation of a medicament for treatment and/or prevention of diseases associated with the increased plasma PLTP activity and/or the increased plasma CETP activity in a mammal, such as atherosclerosis, cardiovascular diseases and peripheral vascular diseases, etc.
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Page/Page column 30
(2009/12/23)
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- Enantioselective synthesis of α-fluorinated β2-amino acids
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A methodology for the enantioselective synthesis of α-fluorinated β2-amino acids has been developed from readily available carboxylic acids 3. Conversion to the Evan's oxazolidinone followed by enantioselective fluorination and alkylation gave 7 in high diastereomeric excess (>95%). Subsequent removal of the oxazolidinone and amination at the Bn-protected hydroxyl center gave optically active α-fluorinated β2-amino acids.
- Edmonds, Michael K.,Graichen, Florian H.M.,Gardiner, James,Abell, Andrew D.
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body text
p. 885 - 887
(2009/04/07)
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- Potent platelet-derived growth factor-β receptor (PDGF-βR) inhibitors: Synthesis and structure-activity relationships of 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl} quinoxalin-2(1H)-one derivatives
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We found previously that 7-[3-(cyclohexylmethyl)ureido]-3-{1-methyl-1H- pyrrolo[2,3-b]pyridin-3-yl}quinoxalin-2(1H)-one (7d-6) has considerable potency as a PDGF inhibitor. This compound showed potent inhibitory activity in a PDGF-induced CPA (Cell Proliferation Assay) and APA (Auto-Phosphorylation Assay) (IC50=0.05 μmol/l in CPA, 0.03 μmol/l in APA). Therefore, we tried to develop a novel and effective PDGF-βR inhibitor by optimizing a series of its derivatives. We found that trifluoroacetic acid (TFA)-catalyzed coupling of pyrrolo[2,3-b]pyridines with quinoxalin-2-ones proceeded efficiently under mild oxidation condition with manganese(IV) oxide (MnO2) in situ, so this method was applied to prepare a series of derivatives. Results of in vitro screening of newly synthesized derivatives identified compound 7d-9 as having potent (IC50=0.014 μmol/l in CPA, 0.007 μmol/l in APA) and selective [IC50 values against vascular endothelial growth factor receptor 2 (VEGFR2, kinase domain region, KDR), epidermal growth factor receptor (EGFR), c-Met (hepatocyte growth factor receptor) and insulin growth factor I receptor (IGF-IR)/IC50 against PDGFR were each >1000] inhibitory activity. Moreover, in this series of derivatives, 7b-2 showed potent inhibitory activity toward both PDGF- and VEGF-induced signaling (PDGFR: IC50=0.004 μmol/l in CPA, 0.0008 μmol/l in APA, KDR: IC 50=0.008 μmol/l in APA). Herein we report a new and convenient synthetic method for this series of derivatives and its SAR study.
- Aoki, Katsuyuki,Obata, Tatsuhiro,Yamazaki, Yosuke,Mori, Yoshikazu,Hirokawa, Hiroko,Koseki, Jun-Ichi,Hattori, Tomohisa,Niitsu, Kazuaki,Takeda, Shuichi,Aburada, Masaki,Miyamoto, Ken-Ichi
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p. 255 - 267
(2007/10/03)
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- Privileged structure based ligands for melanocortin-4 receptors-Aliphatic piperazine derivatives
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Aliphatic carbocyclic replacement of the benzyl group of compound 1 yielded compounds with high affinity for the melanocortin-4 receptor (MC4R). Compounds with a cyclohexyl group showed a consistent high affinity, while different polar groups with less basicity were good replacements for the original diethyl amines. Substitution of the polar group found in these privileged structures with an aliphatic moiety produced compounds with high affinity for MC4R.
- Briner, Karin,Collado, Iván,Fisher, Matthew J.,García-Paredes, Cristina,Husain, Saba,Kuklish, Steven L.,Mateo, Ana I.,O'Brien, Thomas P.,Ornstein, Paul L.,Zgombick, John,de Frutos, óscar
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p. 3449 - 3453
(2007/10/03)
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- α-Aminoalkylphosphonates as a tool in experimental optimisation of P1 side chain shape of potential inhibitors in S1 pocket of leucine- and neutral aminopeptidases
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The synthesis and biological activity studies of the series of structurally different α-aminoalkylphosphonates were performed in order to optimise the shape of the side chain of the potential inhibitors in S1 pocket of leucine aminopeptidase [E.C.3.4.11.1]. Analysis of a series of compounds with aromatic, aliphatic and alicyclic P1 side chains enabled to find out the structural features, optimal for that fragment of inhibitors of LAP. The most active among all investigated compounds were the phosphonic analogues of homo-tyrosine (Ki = 120:nM) and homo-phenylalanine (Ki = 140:nM), which even as racemic mixtures were better inhibitors in comparison with the best till now-phosphonic analogue of l-leucine (230 nM). Additional comparison of the inhibitory activity obtained for aminopeptidase N (APN, E.C.3.4.11.2) give insight into structural preferences of both enzymes.
- Drag, Marcin,Grembecka, Jolanta,Pawelczak, Malgorzata,Kafarski, Pawel
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p. 764 - 771
(2007/10/03)
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- Chemical process and new intermediates
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Process for the preparation of a compound of the general formula (I) and pharmaceutically acceptable salts and solvates thereof, (I) characterised by reacting an N-(amino-tioxo-methyl)-1H-indole-2-carboxamide of the general formula (II), with an α-halogen-ketone of the general formula (III), wherein X stands for halogen.
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- Synthesis and microbiological activity of some novel N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives
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The synthesis and microbiological activity of a new series of N-[2-(p-substitutedphenyl)-5-benzoxazolyl]-cyclohexyl carboxamide, -cyclohexyl acetamide and -cyclohexyl propionamide derivatives (4-11) is described. The in vitro microbiological activity of the compounds was determined against Gram-positive, Gram-negative bacteria and the yeast Candida albicans in comparison with standard drugs. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms.
- Temiz Arpac, Oezlem,Ener, Esin Ak,Yalcn, Ismail,Altanlar, Nurten
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p. 771 - 775
(2007/10/03)
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- Anthranilamides: New antimicroalgal active substances from a marine Streptomyces sp
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2-[Methyl-(3-phenylpropionyl)amino]-benzoic acid (1e) was isolated from a culture of marine Stretomyces sp. strain B7747. Analogous compounds have potential importance as phytotoxic substances, hence compound 1e and the analogues 1a-1d and 1f-3a were synthesised. Antimicroalgal activity of the anthranilamide analogues showed that esters 1b, 1f and 2b were more active than the free acids. The minimum inhibitory concentration (MIC) against Chlorella vulgaris, Chlorella solokiniana, Chlorella salina and Scenedesmus subspicatus ranged from 20 to 107 μg/ml. All anthranilamides were inactive against Staphylococcus aureus, Escherichia coli, and Mucor miehei.
- Farooq Biabani,Baake, Matthias,Lovisetto, Barbara,Laatsch, Hartmut,Helmke, Elisabeth,Weyland, Horst
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p. 333 - 340
(2007/10/03)
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- Penultimate group effects in free radical telomerizations of acrylamides
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The telomerization of several acrylamides, most containing chiral auxiliary groups, was investigated. The first-formed stereogenic center in the n = 2 telomer (the penultimate center) has a significant effect on the configuration of the second (ultimate) center in the product. The penultimate chiral center of oxazolidine-derived acrylamides directs the configuration of the ultimate center such that the erythro n = 2 product is preferred. Sultam-substituted acrylamides preferentially lead, on the other hand, to threo products or give products with little stereoselectivity.
- Porter, Ned A.,Carter, Randall L.,Mero, Christopher L.,Roepel, Michael G.,Curran, Dennis P.
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p. 4181 - 4198
(2007/10/03)
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- Origins of stereoselectivity in radical additions: Reactions of alkenes and radicals bearing oxazolidine and thiazolidine amide groups
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Single-crystal X-ray analysis of four alkenes that undergo stereoselective radical addition reactions are reported. The facial selectivity of radical additions to these alkenes is understood based upon their solid-state conformations. Alkenes which have a conformation placing a group at a position in space sterically protecting one of the faces from addition undergo radical addition with diastereofacial selectivity. The structures of the alkenes are analyzed by the polar coordinates of groups relative to the alkene center undergoing addition. The analysis of conformations of alkenes also provides a rationale for stereoselectivity in the reactions of radicals derived from the alkenes. Factors which influence the conformation of the alkene also apparently influence the conformation of analogous radicals. Several products of addition were also subjected to X-ray cryslallographic analysis, and the steric factors which influence the conformation of the reactant alkene are also observed to affect the conformation of the radical addition products.
- Porter, Ned A.,Rosenstein, Ian J.,Breyer, Robert A.,Bruhnke, John D.,Wu, Wen-Xue,McPhail, Andrew T.
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p. 7664 - 7676
(2007/10/02)
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- Highly Stereocontrolled Total Synthesis of Leukotriene B4, 20-Hydroxyleukotriene B4, Leukotriene B3, and Their Analogues
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A highly stereocontrolled and practical new method for synthesis of LTB4 (1), 20-OH-LTB4 (2), and LTB3 (3) has been developed, which uses the palladium catalyzed coupling reaction of the vinylborane 5, derived from the C(1)-C(9) fragment 4, with the corresponding C(10)-C(20) fragments 6a-c.The acetylene 4 was synthesized by palladium-copper-catalyzed coupling reaction of (trimethylsilyl)acetylene with the bromide 12, which was prepared from γ-(trimethylsilyl)allylic alcohol (S)-10 by bromination followed by debromosilylation.The alcohol (S)-10 was obtained by the kinetic resolution of the racemate dl-10 using the Sharpless reagent.The vinyl iodides 6a and 6b were prepared from racemic γ-(trimethylsilyl)allylic alcohols dl-17 and dl-28, respectively, by the Sharpless kinetic resolution followed by the reactions taking advantage of the reactivity of vinylsilane moiety, while the segment 6c was prepared by the Sharpless kinetic resolution of racemic γ-iodoallylic alcohol dl-34 followed by protection.By using this method, precursors of the radiolabeled LTB4, and 20-OH-LTB4, i.e., 14,15-didehydro-LTB4 (40) and 14,15-didehydro-20-OH-LTB4 (41), respectively, were also synthesized.Similarly the novel structural analogue of LTB 42-44 were prepared.
- Kobayashi, Yuichi,Shimazaki, Toshiyuki,Taguchi, Hideki,Sato, Fumie
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p. 5324 - 5335
(2007/10/02)
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- MESOMORPHOGENS. VI. CHOLESTERYL AND THIOCHOLESTERYL ESTERS OF CYCLOALKANECARBOXYLIC ACIDS
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The acylation of cholesterol and thiocholesterol by acid chlorides of ω-cycloalkane carboxylic acid gave the cholesteryl and thiocholesteryl esters of the corresponding acids.The mesogenic capacity of the ω-cycloalkanoates of cholesterol and thiocholesterol is largely a factor of the polarizability of these molecules and not their spatial configuration.A decrease in the geometric anisotropy and concurrent increase in polarizability impart instability to the meso phase of most ω-cycloalkanoates.
- Bogatskii, A. V.,Kondrat'eva, R. V.,Galatina, A. I.,Novikova, N. S.
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p. 1286 - 1290
(2007/10/02)
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