Synthesis, crystal structure and cytokinin activities of β-substituted 6-styrylpurines

Nishikawa, Shiro; Yamashita, Fumio; Kashimura, Naoki; Kumazawa, Zenzaburo; Oogami, Naoko; Mizuno, Hiroshi

doi:10.1016/s0031-9422(00)89504-7

Cited by 10 publications

(9 citation statements)

References 13 publications

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“…Purines bearing a 6-ethynyl or 6-vinyl moiety also undergo conjugate addition reactions with nitrogen, oxygen and sulfur nucleophiles. 16,17 To assess the reactivity of selected heterocycles substituted with an ethynyl or vinyl group (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), and hence their potential as inhibitors of Nek2 kinase, we have performed a model study in which these compounds were reacted with N-acetylcysteine methyl ester (13) (Scheme 1). By modifying the core heterocycle of the molecules and substituents, surprising differences in reactivity were observed using the quantitative 1 H NMR (qNMR) method.…”

Section: Introductionmentioning

confidence: 99%

Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles

et al. 2014

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Recent studies have shown that irreversible inhibition of Nek2 kinase [(Never in mitosis gene a)-related kinase 2], overexpression of which is observed in several cancers, can be achieved using Michael acceptors containing an ethynyl group, which target the enzyme's cysteine 22 residue lying near the catalytic site. The model studies described herein demonstrate an analogous capture of the ethynyl moiety in a series of ethynyl-heterocycles (e.g. 6-ethynyl-N-phenyl-9H-purin-2-amine) by N-acetylcysteine methyl ester in the presence of 1,4-diazabicyclo[2.2.2]octane in either dimethyl sulfoxide or N,N-dimethylformamide. Kinetic studies showed a 50-fold range in reactivity with 7-ethynyl-N-phenyl-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine being the most reactive compound, whereas 4-ethynyl-N-phenyl-7H-pyrrolo[2,3-d]pyrimidin-2-amine was the least reactive. Studies of the isomeric compounds, 2-(3-((6-ethynyl-7-methyl-7H-purin-2-yl)amino)phenyl)acetamide and 2-(3-((6-ethynyl-9-methyl-9H-purin-2-yl)amino)phenyl)acetamide, revealed the N(7)-methyl isomer to be 5-fold more reactive than the 9-methyl isomer, which is ascribed to a buttressing effect in the N(7)-methyl compound. Comparison of the crystal structures of these isomers showed that the ethynyl group is significantly displaced away from the methyl group exclusively in the N(7)-methyl isomer with an sp(2) bond angle of 124°, whereas the corresponding angle in the N(9)-methyl isomer was the expected 120°. The results of this study indicate heterocyclic scaffolds that are likely to be more promising for inhibition of Nek2 and other kinases containing a reactive cysteine.

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Section: Introductionmentioning

confidence: 99%

Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles

et al. 2014

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“…For these N-alkyl and N-acyl derivatives, analogous modification is also available. In fact, 6-trans-styrylpurine derivative 4 (Nishikawa et al, 1985(Nishikawa et al, , 1994 and 4-styrylpyrimidine derivative 5 (Nishikawa et al, 1989) promoted significantly the growth of tobacco callus tissues as well as the betacyanin biosynthesis of Amaranthus seedlings. These results indicate that the exocyclic nitrogen atoms of N 6substituted adenines can be replaced with a sp 2 carbon atom without lowering their cytokinin activity.…”

Section: Introductionmentioning

confidence: 99%

“…high efficiency. Simple addition of small molecules including hydrogen halide, alcohol, and mercaptan to 7 together with E-Z-photoisomerization would provide β-substituted (Z)-and (E)-4-styrylpyridines, as in the cases of 6-styrylpurines (Nishikawa et al, 1985(Nishikawa et al, , 1994 and 4-styrylpyrimidines (Nishikawa et al, 1989). Thus we have synthesized some β-substituted 4-styrylpyridines conveniently from commercially available 4-bromopyridine (6) via alkynyl compound 7 prepared by the palladium-catalyzed coupling and tested their cytokinin activity in both betacyanin and tobacco callus bioassays.…”

Section: Introductionmentioning

confidence: 99%

Convenient Synthesis and Cytokinin Activity of β-Substituted 4-Styrylpyridines, the Simplest Cytokinin Analogs with a Moderate Cell Division-Promoting Activity

Nishikawa

Sato

Kojima

et al. 1996

J. Agric. Food Chem.

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Designed synthesis of Z-and E-isomers of β-substituted 4-styrylpyridines as cytokinin analogs was conveniently achieved by nucleophilic and electrophilic addition of ethanol, methyl mercaptan, and hydrogen halides (HCl, HBr, and HI) to 4-(phenylethynyl)pyridine prepared by palladium-catalyzed coupling. They easily underwent E-Z photoisomerization under monochromatic UV light or sunlight. A tobacco callus assay revealed that the Z-isomers were more active than their E-isomers and that the Z-ethoxy derivative, which showed the highest activity among the β-substituted 4-styrylpyridines, was one-fifth as potent as kinetin. The Z-ethoxy derivative also promoted betacyanin biosynthesis of Amaranthus seedlings at 4-100 µM.

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“…[3] This class of compounds also exhibits broad biological activities and many natural or synthetic products contain av inylchloride moiety. [4][5][6][7] Therefore,t he straightforward regio-and stereoselective synthesis of vinylchlorides is highly desirable.V inylchlorides mainly arise from carbonyl compounds, [6,8] by ah alogenation reaction with harmful, traditional phosphorous reagents or acid chlorides,o rf rom alkynes. [9] Thes toichiometric formation of ab oron or metal vinyl intermediate from alkynes,f ollowed by addition of ac hloride,i saclassical process to provide chloroalkenes.…”

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confidence: 99%

Selective Ruthenium‐Catalyzed Hydrochlorination of Alkynes: One‐Step Synthesis of Vinylchlorides

2015

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An unprecedented ruthenium-catalyzed direct and selective alkyne hydrochlorination is reported and leads to vinylchlorides in excellent yields with atom economy. The reaction proceeds at room temperature from terminal alkynes and provides a variety of chloroalkenes. Only the regioisomer resulting from the formal Markovnikov addition is selectively formed. Mechanistic studies show the stereoselective syn addition of HCl to alkynes at room temperature and suggest a chloro hydrido Ru(IV) species as a key intermediate of the reaction.

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Synthesis, crystal structure and cytokinin activities of β-substituted 6-styrylpurines

Cited by 10 publications

References 13 publications

Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles

Model system for irreversible inhibition of Nek2: thiol addition to ethynylpurines and related substituted heterocycles

Convenient Synthesis and Cytokinin Activity of β-Substituted 4-Styrylpyridines, the Simplest Cytokinin Analogs with a Moderate Cell Division-Promoting Activity

Selective Ruthenium‐Catalyzed Hydrochlorination of Alkynes: One‐Step Synthesis of Vinylchlorides

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