- Rhodium-catalyzed oxidative coupling of benzoic acids with propargyl alcohols: An efficient access to isocoumarins
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An efficient protocol of Rh(III)-catalyzed oxidative cyclization of benzoic acids with propargyl alcohols to give substituted isocoumarins under mild conditions was reported. A variety of substrates were applied in this reaction in yields up to 89%.
- Luo, Feihua,He, Shuhua,Gou, Quan,Chen, Jinyang,Zhang, mingzhong
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supporting information
(2020/12/29)
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- Rhodium-Catalyzed Annulation of Phenacyl Ammonium Salts with Propargylic Alcohols via a Sequential Dual C-H and a C-C Bond Activation: Modular Entry to Diverse Isochromenones
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Given their omnipresence in natural products and pharmaceuticals, isochromenone congeners are one of the most privileged scaffolds to synthetic chemists. Disclosed herein is a dual (ortho/meta) C-H and C-C activation of phenacyl ammonium salts (acylammonium as traceless directing group) toward annulation with propargylic alcohols to accomplish rapid access for novel isochromenones by means of rhodium catalysis from readily available starting materials. This operationally simple protocol features broad substrate scope and wide functional group tolerance. Importantly, the protocol circumvents the need of any stoichiometric metal oxidants and proceeds under aerobic conditions.
- Nanubolu, Jagadeesh Babu,Reddy Singam, Maneesh Kumar,Sridhar Reddy, Maddi,Suresh, Vavilapalli,Suri Babu, Undamatla
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supporting information
p. 7888 - 7893
(2021/10/25)
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- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
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-
Paragraph 00230; 00437
(2020/07/05)
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- Palladium(II)/Lewis acid cocatalyzed oxidative annulation of 2-alkenylanilines and propargylic esters: An access to benzo[ b]azepines
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An attractive approach to valuable yet synthetically challenging benzo[b]azepines was established via palladium(II)/Lewis acid cocatalyzed oxidative [5 + 2] annulation of readily available 2-alkenylanilines and propargylic esters. The protocol features mild reaction conditions and good functional group tolerance, constituting an array of benzo[b]azepines in yields of 30-75%.
- Qiao, Hong,Zhang, Shengjun,Li, Kangkang,Cao, Zhengqiang,Zeng, Fanlong
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p. 10843 - 10851
(2019/09/12)
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- Sonogashira-Hagihara and Buchwald-Hartwig cross-coupling reactions with sydnone and sydnone imine derived catalysts
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Seven different palladium complexes of sydnones and sydnone imines and a co-catalyst system consisting of lithium sydnone-4-carboxylate and Pd(PPh3)4 catalyzed Sonogashira-Hagihara reactions between (hetero)- aromatic bromides and 2-methylbut-3-yn-2-ol (52 examples, up to 100% yield). The co-catalyst system and a sydnone Pd complex were also tested in Buchwald-Hartwig reactions (9 examples, up to 100% yield). (Equation Presented).
- Lücke, Ana-Luiza,Pruschinski, Lucas,Freese, Tyll,Schmidt, Andreas
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supporting information
p. 94 - 104
(2020/08/26)
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- Chemistry and spectroscopy of cross-conjugated and pseudo-cross-conjugated quinolinium-ethynyl-benzoate mesomeric betaines
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The three isomers 1-methylquinolinium-2-, 3-, and 4-ethynyl(phenyl-4-carboxylates) belong to two distinct types of heterocyclic mesomeric betaines. The quinolinium substituted in position 3 is a cross-conjugated mesomeric betaine (CCMB), whereas the quinolinium derivatives substituted in positions 2 and 4 are members of the class of pseudo-cross-conjugated mesomeric betaines (PCCMBs). While the charges are strictly separated within the common π-electron system of the CCMB according to the canonical formulae, the charges are effectively but not exclusively delocalized in the PCCMBs because cumulenoid resonance forms including electron sextet structures without external octet stabilization can be formed in accordance with the definition of PCCMBs. As a consequence, despite being closely related structures, the three isomers differ in their chemical and spectroscopic behaviors. Thus, on trying to hydrolyze the ester group of the methyl quinolinium-2-ethynyl-benzoate into the corresponding acid by subsequent treatment with sodium hydroxide in methanol and aqueous hydrochloric acid at pH 3, the acetal methyl 1,1-dimethoxy-2-(quinolinium-ylidene)ethyl]benzoate and the corresponding β-enamino carbonyl compound were formed, respectively. The corresponding acids of the 2- and 4-substituted quinolinium-ethynyl-benzoates were obtained by a modified procedure. On deprotonation, the resulting cross-conjugated quinolinium-3-ethynyl-benzoate betaine proved to be stable, whereas the corresponding pseudo-cross-conjugated quinolinium-2- and -4-ethynyl-benzoate betaines decomposed. Frontier orbital profiles were calculated, and IR and Raman spectra of the starting materials were measured and calculated to analyze the differences of CCMBs and PCCMBs of mesomeric betaines possessing triple bonds. A higher contribution of the cumulenoid resonance forms to the overall structure of the PCCMBs was determined.
- Batsyts, Sviatoslav,Ramírez, Francisco J.,Casado, Juan,Namyslo, Jan C.,Schmidt, Andreas
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p. 481 - 491
(2018/05/30)
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- Hydrotalcite-supported palladium nanoparticles as catalysts for the hydroarylation of carbon-carbon multiple bonds
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Palladium nanoparticles supported on Mg/Ca hydrotalcites catalyze the hydroarylation reaction of different alkynes and alkenes with aryl iodides under air in MeCN. The reaction of tertiary propargylic alcohols (1) with aryl iodides (2) yields, stereoselectively, γ,γ-diarylallylic alcohols (3) in moderate to high yields and high selectivity. Also, the HT/Pd hydroarylation reaction with aryl iodides was attempted on norbornene and α,β-unsaturated ketones affording, respectively, exo-aryl bicyclo[2.2.1]heptanes and β-aryl ketones in moderate to high yields. All the reactions described benefit from using a heterogeneous catalyst with evident advantages in terms of reaction purification and recyclability of the catalyst.
- Di Nicola,Arcadi,Gallucci,Mucciante,Rossi
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supporting information
p. 1952 - 1957
(2018/02/09)
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- Benzophenanthrene benzoyloxy benzene bridged perylene bisimide diester synthetic method
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The invention provides a benzophenanthrene benzoyloxy benzene bridged perylene bisimide diester synthetic method. A synthesis route is characterized in that 1) p-acetenyl benzoic acid is synthesized; monohydroxy pentahexyloxy benzophenanthrene is generated; a benzophenanthrene derivative containing terminal alkyne is finally prepared; 2) N-(4-iodophenyl)perylene imine dioctyl phthalate diester is generated; and 3) an intermediate obtained by the above two parts, and a benzophenanthrene benzoyloxy benzene bridged perylene bisimide diester binary compound is obtained through a reaction by a Sonogashira cross-coupling reaction. The benzophenanthrene and its derivative are most widely discotic liquid crystal material in the prior art, have good photoelectric property, and can easily form a cylindrical liquid crystalline phase, a perylene imide derivative has strong electronic capacity, has high electronic affinity, has strong absorption capacity at a visible light zone, and is an excellent n-type organic semiconductor material. The discotic liquid crystal binary compound with an electron donor (D)-bridge (B)-acceptor (A) structure is designed and synthesized, and can be used for molecule devices of an organic photovoltaic material, a liquid crystal material, an organic solar energy cell, and an organic light-emitting diode.
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Paragraph 0015; 0016
(2017/09/01)
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- Synthesizing method of benzophenanthrene benzoyloxy alkynylphenyl alkynylphenyl bridged perylene mono-imide dihexyl ester
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The invention aims at providing a synthesizing method of benzophenanthrene benzoyloxy alkyne benzyne benzene bridged perylene mono-imide dihexyl ester. A synthesizing path of the synthesizing comprises the first part of synthesizing iodine-containing phenyl ethynyl benzoyloxy penta-hexyloxy benzophenanthrene, the second part of utilizing 3,4,9,10-perylene tetracarboxylic acid anhydride as a raw material and synthesizing alkyne-containing phenyl perylene bisimide diester derivative and the third part of synthesizing intermediates obtained through the first part and the second part into benzophenanthrene oxycarbonyl phenylalkynylphenyl alkynylphenyl bridged perylene mono-imide dihexyl ester binary compound through Sonogashira cross coupling reaction. Benzophenanthrene and derivative of the benzophenanthrene are disc-shaped liquid crystal materials which are most extensively utilized currently, and perylene bisimide derivative is an excellent n type organic semiconductor material. The synthesizing method disclosed by the invention designs and synthesizes disc-shaped liquid crystal binary compound containing an electron donor-bridge-receptor structure, and the compound can be applied to molecular devices of organic solar cells, organic light emitting diodes and the like.
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Paragraph 0015; 0016
(2017/09/01)
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- Synthesis method of triphenylene benzoyloxy alkynyl biphenyl alkynyl benzene bridged perylene monoimine dihexyl ester
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The invention aims at providing a synthesis method of triphenylene oxycarbonyl phenylacetylenic biphenyl alkyne benzene bridged perylene monoimine dihexyl ester. The synthesis method comprises the synthesis routes: firstly, synthesizing iodine-containing biphenylyl acetenyl benzoyloxy pentaoctoxytriphenylene; secondly, synthesizing an alkyne-containing phenyl perylene imide diester derivative by taking perylene tetracarboxylic anhydride as a raw material; and thirdly, carrying out Sonogashira cross-coupling reaction on an intermediate obtained by the two steps to synthesize a triphenylene oxycarbonyl phenylacetylenic biphenyl alkyne benzene bridged perylene monoimine dihexyl ester binary compound. Triphenylene and a derivative thereof are discoid liquid crystal materials most extensively applied at present, while a perylene imide derivative is a favorable N-type organic semiconductor material. The invention designs and synthesizes a discoid liquid crystal binary compound with an electron donor-bridge-receptor structure, and the compound can be applied to molecular devices such as organic solar cells and organic light-emitting diodes.
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-
Paragraph 0015; 0016
(2017/12/29)
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- Cyclization of Diaryl(hetaryl)alkynes under Selenobromination Conditions: Regioselectivity and Mechanistic Studies
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The cyclization of substituted diaryl(hetaryl)alkynes with in-situ-prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b]selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials. The reactions can be performed in air without the use of moisture-sensitive reagents, dry solvents, or an inert atmosphere. Mechanistic studies confirmed a regioselective anti 1,2-addition in the selenobromination step, and a subsequent electrophilic substitution in the aromatic ring to complete the cyclization. The cyclization of substituted diaryl(hetaryl)alkynes with in-situ-prepared SeBr4 has been achieved. The use of an alkene additive as a bromine scavenger gives simple access to functionalized benzo[b]selenophene and selenophenothiophene derivatives from commercially available or easily accessible starting materials.
- Paegle, Edgars,Belyakov, Sergey,Petrova, Marina,Liepinsh, Edvards,Arsenyan, Pavel
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supporting information
p. 4389 - 4399
(2015/07/27)
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- Water-soluble nano-fluorogens fabricated by self-assembly of bolaamphiphiles bearing AIE moieties: Towards application in cell imaging
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Nano-fluorogens with a mono-molecule layered structure are fabricated by self-assembly of a new bolaamphiphile bearing a tetraphenylethene moiety. The nano-fluorogens show good water-solubility, biocompatibility, and strong emission with a quantum yield as high as 15%. The nano-fluorogens, as prepared, are successfully applied to label and map HeLa cells. The images obtained have high contrast and resolution, showing a promising potential for fluorescence detection in bio-related systems.
- Xia, Yijun,Dong, Lin,Jin, Yingzhi,Wang, Shuai,Yan, Li,Yin, Shouchun,Zhou, Shixin,Song, Bo
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p. 491 - 497
(2015/02/19)
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- Palladium-catalyzed oxidative deacetonative coupling of 4-aryl-2-methyl-3-butyn-2-ols with H-phosphonates
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An efficient and generally applicable protocol for palladium-catalyzed oxidative deacetonative coupling of 4-aryl-2-methyl-3-butyn-2-ols with dialkyl H-phosphonates has been developed. This methodology provides a new and practical route to alkynylphosphonates using the inexpensive 4-aryl-2-methyl-3-butyn-2-ols as the alkyne sources. This reaction could also be performed with aryl bromides, 2-methyl-3-butyne-2-ol and dialkyl H-phosphonates using the cheap 2-methyl-3-butyne-2-ol as an alkyne source. This journal is
- Li, Xiang,Sun, Suyan,Yang, Fan,Kang, Jianxun,Wu, Yusheng,Wu, Yangjie
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p. 2432 - 2436
(2015/03/04)
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- An approach to the selenobromination of aryl(thienyl)alkynes: Access to 3-bromobenzo[b]selenophenes and selenophenothiophenes
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A novel approach for the cyclization of arylalkynes with selenium(IV) bromide prepared in situ has been elaborated. The use of an alkene additive as a bromine scavenger provides a convenient synthetic pathway for the synthesis of a wide variety of 3-bromobenzo[b]selenophenes. Reactions can be performed open to air without the use of moisture-sensitive reagents, anhydrous solvents, or an inert atmosphere. Selenobromination of ethynylthiophenes has been applied for the preparation of selenopheno[3,2-b]- and selenopheno[2,3-b]thiophenes. The molecular structures of representative derivatives have been confirmed by X-ray crystallographic analysis. The use of an alkene additive as a bromine scavenger under selenobromination conditions provides a convenient synthetic pathway for the synthesis of a wide variety of 3-bromobenzo[b]selenophenes in moderate to high yields. The reactions are not moisture-sensitive and do not require an inert atmosphere. Selenobromination of ethynylthiophenes enables the preparation of selenopheno[b]thiophenes. Copyright
- Paegle, Edgars,Belyakov, Sergey,Arsenyan, Pavel
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supporting information
p. 3831 - 3840
(2014/06/24)
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- Mechanochromic behavior of aryl-substituted buta-1,3-diene derivatives with aggregation enhanced emission
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Three tetra-aryl substituted 1,3-butadiene derivatives with aggregation enhanced emission (AEE) and mechanochromic fluorescence behavior have been rationally designed and synthesized. The results suggest an effective design strategy for developing diverse materials with aggregation induced emission (AIE) and significant mechanochromic performance by employing D-π-A structures with large dipole moments. Mechanochromic luminescence: Three tetra-aryl substituted 1,3-butadiene derivatives with distinct electronic push and/or pull substituents have been prepared. All three derivatives show typical aggregation enhanced emission (AEE) features owing to the restriction of intramolecular rotations. The results demonstrate that chromophores with both large dipole moments and AEE characteristics are of benefit for mechanochromic applications with efficient solid-state emissions.
- Zhang, Yijia,Han, Ting,Gu, Shangzhi,Zhou, Tianye,Zhao, Chuanzhen,Guo, Yuexin,Feng, Xiao,Tong, Bin,Bing,Shi, Jianbing,Zhi, Junge,Dong, Yuping
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supporting information
p. 8856 - 8861
(2014/07/22)
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- Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions
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Two efficient protocols for the palladium-catalyzed synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides in the absence of copper were developed. A simple catalytic system consisting of Pd(OAc)2 and P(p-tol)3 using DBU as the base and THF as the solvent was found to be highly effective for the coupling reaction of 2-methyl-3-butyn-2-ol (4) with a wide range of aryl bromides in good to excellent yields. Analogously, the synthesis of aryl-2-methyl-3-butyn-2-ols was performed also through the decarboxylative coupling reaction of 4-hydroxy-4-methyl-2-pentynoic acid with aryl bromides, using a catalyst containing Pd(OAc)2 in combination with SPhos or XPhos in the presence of tetra-n-butylammonium fluoride (TBAF) as the base and THF as the solvent. Therefore, new efficient approaches to the synthesis of terminal acetylenes from widely available aryl bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described.
- Caporale, Andrea,Tartaggia, Stefano,Castellin, Andrea,De Lucchi, Ottorino
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supporting information
p. 384 - 393
(2014/03/21)
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- K3PO4-KOH mixture as efficient reagent for the deprotection of 4-aryl-2-methyl-3-butyn-2-ols to terminal acetylenes
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A mixture of potassium hydroxide and potassium phosphate was found to be an active reagent mixture for the cleavage of 2-hydroxypropyl-protected acetylenes. The reaction was performed in toluene at reflux temperature and gave terminal acetylenes in good to excellent yields within very short periods of time. Numerous other functional groups are tolerated. Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications for full experimental and spectral details.
- Smeyanov, Alexey,Schmidt, Andreas
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p. 2809 - 2816
(2013/08/23)
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- A comparison of X-ray crystal structures including methyl 3,5-bis(hydroxymethyl)benzoate, its phenylethynyl extended derivative in polymorphous forms and the corresponding carboxylic acids
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Considering the specific supramolecular synthon design of carboxylic acid and alcoholic hydroxyl groups in the field of crystal engineering, we compared the solid state structures of particular benzoates and corresponding acids 1-4 both in the non-spacered (1, 2) and spacered (3, 4) forms. Based on the single crystal X-ray study, there is only a slight influence of the phenylacetylene spacer with regard to the layer lattice arrangement of the benzoates while referring to the benzoic acid analogues the addition of the spacer gives rise to a modification of the lattice from a layer to a tape structure. Dependent on the crystallization conditions, two crystalline polymorphs of compound 3 (3a, 3b) were obtained and discussed regarding their structural differences. Springer Science+Business Media, LLC 2011.
- Katzsch, Felix,Eissmann, Diana,Weber, Edwin
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body text
p. 245 - 255
(2012/08/28)
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- Synthesis and characterization of poly(phenylacetylenes) featuring activated ester side groups
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Four monomers based on 4-ethynylbenzoic acid have been synthesized, one of those featuring an activated ester. With the metathesis catalytic system WCl6/Ph4Sn, these acetylenic monomers could successfully be polymerized yielding conjugated polymers with molecular weights of around 10,000 to 15,000 g/mol and molecular weight distributions Mw/M n ≤ 2.1. Also the copolymerization of phenylacetylene or methyl 4-ethynylbenzoate with pentafluorophenyl 4-ethynylbenzoate as reactive unit was conducted. Polymer analogous reactions of the reactive polymers and copolymers with amines have been investigated and it was found that poly(pentafluorophenyl 4-ethynylbenzoate) featured a significant reactivity, such that reactions proceeded quantitatively even with aromatic amines. Moreover the UV-Vis spectra of the activated ester based polymer before and after conversion with aliphatic amines showed a change, indicating an effect on the conjugated backbone of the polymers. Copyright
- Pauly, Anja C.,Theato, Patrick
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experimental part
p. 211 - 224
(2011/09/16)
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- Synthesis of 3-tert-butyl-5-(4-vinylphenyl)-1,2,4-oxadiazole using two different pathways
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3-tert-butyl-5-(4-vinylphenyl)-1,2,4-oxadiazole (1) has been synthesized in two different ways, using 3-tert-butyl-5-(4-ethynylphenyl)-1,2,4-oxadiazole (2) or 4-(3-tert-butyl-1,2,4-oxadiazol-5-yl)benzaldehyde (3) as intermediates. The structure of compound 3 was confirmed by X-ray diffraction. 1,2,4-Oxadiazoles have been prepared using 1,1-carbonyldiimidazole (CDI) as a reagent for both formation and cyclodehydration of O-acyl-amidoximes. The use of CDI facilitates parallel purification of the oxadiazole products by simple liquid-liquid extraction and filtration. The heterocycles were obtained in good yields and in relatively short reaction times.
- Maftei, Catalin-Vasile,Fodor, Elena,Mangalagiu, Ionel,Jones, Peter G.,Daniliuc, Constantin-Gabriel,Franz, Heiko M.,Neda, Ion
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experimental part
p. 989 - 994
(2012/01/19)
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- Smectic aggregates of sheet-like side-chain liquid crystalline polyacetylenes directly formed during solution polymerization
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We have successfully synthesized two side-chain liquid crystalline polyacetylenes (denoted as P3-5 and P2-5) with the mesogenic units based on a "phenyl-ester-phenyl" motif directly linked to the semirigid polyacetylene backbone in a terminal-on mode without flexible spacer. During the polymerization catalyzed by Rh(nbd)[B(C6H5)4] in toluene, the resultant polymers (or oligomers) automatically precipitate out of the polymerization solution as red solids, which cannot be dissolved in common organic solvents. Wide-angle X-ray diffraction results confirm that the polymer precipitates possess a smectic (or sanidic) structure, suggesting that the molecules without flexible spacers are sheet-like and can stack parallel to each other during polymerization. We in situ monitored the solution polymerization and the aggregation processes using UV-visible and 1H NMR spectroscopy methods. The experimental results indicate that after reaching a critical molecular weight the P3-5 and P2-5 molecules self-aggregate in solution and that the smectic aggregation proceeds during the solution polymerization. An apparent first-order polymerization kinetics can be obtained after the polymerization and aggregation slowed down. The resultant polymers are cis-rich with the main-chain absorption at ~455 nm. This implies that a considerably long effective conjugation length is achieved in the sheet-like cis-rich polyacetylene derivatives.
- Liu, Lu-Mei,Liu, Kai-Peng,Dong, Yu-Ping,Chen, Er-Qiang,Tang, Ben Zhong
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experimental part
p. 6014 - 6023
(2011/10/19)
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- Efficient synthesis of maleimides and carbazoles via Zn(OTf) 2-catalyzed tandem annulations of Lsonitriles and allenic esters
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Lewis acid Zn(OTf)2-catalyzed tandem annulations of isonitriles and allenic esters which lead to efficient and flexible syntheses of a range of biologically significant maleimides and carbazoles and related compounds are reported. A mechanistic rationale is proposed to account for the observed reactivity.
- Li, Yuanzhen,Zou, Haixia,Gong, Jianxian,Xiang, Jing,Luo, Tuoping,Quan, Junmin,Wang, Guoxin,Yang, Zhen
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p. 4057 - 4060
(2008/02/11)
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- Diminished helical character in para-substituted cis-transoidal polyphenylacetylenes due to intramolecular cyclization
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The cis-transoidal PPA helix undergoes irreversible structural changes related to 6π electrocyclization of 1,3-cis-5-hexatriene sequences in the polymer backbone. The dynamics of the helical conformation is evaluated by optical rotation or circular dichroism (CD) spectra at various temperatures. Helical cis- and trans-poly(alkylacetylenes) exhibit different CD spectra in solutions. In the solution, 1,3-cis-5-hexatriene sequences in PPA and its substituted analogues undergo electrocyclization to form cyclohaxadiene repeat units. The results show that literature data on helical PPA are only qualitative as no complete structural analysis was reported in any previous studies.
- Percec, Virgil,Rudick, Jonathan G.,Aqad, Emad
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p. 7205 - 7206
(2007/10/03)
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- New 2,4-Diamino-5-(2′,5′-substituted benzyl)pyrimidines as Potential Drugs against Opportunistic Infections of AIDS and Other Immune Disorders. Synthesis and Species-Dependent Antifolate Activity
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In a continuing effort to design small-molecule inhibitors of dihydrofolate reductase (DHFR) that combine the enzyme-binding selectivity of 2,4-diamino-5-(3′,4′,5′-trimethoxybenzyl)-pyrimidine (trimethoprim, TMP) with the potency of 2,4-diamino-5-methyl-6-(2′ ,5′-dimethoxybenzyl)pyrido[2,3-d]pyrimidine (piritrexim, PTX), seven previously undescribed 2,4-diamino-5-[2′-methoxy-5′-(substituted benzyl)]pyrimidines were synthesized in which the substituent at the 5′-position was a carboxyphenyl group linked to the benzyl moiety by a bridge of two or four atoms in length. The new analogues were all obtained from 2,4-diamino-5-(5′-iodo-2′-methoxybenzyl)pyrimidine via a Sonogashira reaction, followed, where appropriate, by catalytic hydrogenation. The new analogues were tested as inhibitors of DHFR from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three life-threatening pathogens often found in AIDS patients and individuals whose immune system is impaired as a result of treatment with immunosuppressive chemotherapy or radiation. The selectivity index (SI) of each compound was obtained by dividing its 50% inhibitory concentration (IC50) against Pc, Tg, or Ma DHFR by its IC50 against rat DHFR. 2,4-Diamino-[2′-methoxy-5′-(3-carboxyphenyl)-ethynylbenzyl] pyrimidine (28), with an IC50 of 23 nM and an SI of 28 in the Pc DHFR assay, had about the same potency as PTX and was 520 times more potent than TMP. As an inhibitor of Tg DHFR, 28 had an IC50 of 5.5 nM (510-fold lower than that of TMP and similar to that of PTX) and an SI value of 120 (2-fold better than TMP and vastly superior to PTX). Against Ma DHFR, 28 had IC50 and SI values of 1.5 nM and 430, respectively, compared with 300 nM and 610 for TMP. Although it had 2.5-fold lower potency than 28 against Ma DHFR (IC50 = 3.7 nM) and was substantially weaker against Pc and Tg DHFR, 2,4-diamino-[2′-methoxy-5′ -(4-carboxyphenyl)ethynylbenzyl]pyrimidine (29), with the carboxy group at the para rather than the meta position, displayed 2200-fold selectivity against the Ma enzyme and was the most selective 2,4-diamino-5-(5′-substituted benzyl)pyrimidine inhibitor of this enzyme we have encountered to date. Additional bioassay data for these compounds are also reported.
- Rosowsky, Andre,Forsch, Ronald A.,Sibley, Carol Hopkins,Inderlied, Clark B.,Queener, Sherry F.
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p. 1475 - 1486
(2007/10/03)
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- An easily accessible resin-supported palladium catalyst for Sonogashira coupling
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Readily available aminomethyl-polystyrene beads can be transformed in a one-pot reaction to an air-stable polymer-bound chelate phosphine, which can be used for the immobilization of homogeneous catalysts. Such prepared Pd catalysts have proven to be useful reagents for mediating Sonogashira-coupling reactions.
- Gonthier, Elisabeth,Breinbauer, Rolf
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p. 1049 - 1051
(2007/10/03)
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- Water-soluble polymer-bound, recoverable palladium(0)-phosphine catalysts
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The synthesis of a water-soluble polymer-bound Pd(0)-phosphine catalyst is described. This soluble polymeric catalyst is soluble in aqueous or mixed aqueous/organic media and has high activity in nucleophilic allylic substitution and in sp-sp2 coupling reactions of aryl iodides with terminal alkynes. The catalyst can be recycled efficiently by solvent or thermal precipitation methods.
- Bergbreiter, David E.,Liu, Yun-Shan
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p. 7843 - 7846
(2007/10/03)
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