- Pilot in Vivo Structure-Activity Relationship of Dihydromethysticin in Blocking 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone-Induced O6-Methylguanine and Lung Tumor in A/J Mice
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(+)-Dihydromethysticin was recently identified as a promising lung cancer chemopreventive agent, while (+)-dihydrokavain was completely ineffective. A pilot in vivo structure-activity relationship (SAR) was explored, evaluating the efficacy of its analogs in blocking 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced short-term O6-methylguanine and long-term adenoma formation in the lung tissues in A/J mice. Both results revealed cohesive SARs, demonstrating that the methylenedioxy functional group in DHM is essential while the lactone functional group tolerates modifications.
- Puppala, Manohar,Narayanapillai, Sreekanth C.,Leitzman, Pablo,Sun, Haifeng,Upadhyaya, Pramod,O'Sullivan, M. Gerard,Hecht, Stephen S.,Xing, Chengguo
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p. 7935 - 7940
(2017/10/06)
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- Biomimetic iterative method for polyketide synthesis
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An iterative method for synthesizing polyketides was demonstrated, in which the chain elongation of a carboxylic acid was performed by decarboxylative dehydration condensation with a malonic acid half thioester. After transforming the resulting β-ketothioester into an appropriate form, the carboxylic acid functionality was regenerated for the next elongation step.
- Akagawa, Kengo,Kudo, Kazuaki
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supporting information
p. 8645 - 8648
(2017/08/10)
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- Characterisation of the broadly-specific O-methyl-transferase jerf from the late stages of jerangolid biosynthesis
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We describe the characterisation of the O-methyltransferase JerF from the late stages of jerangolid biosynthesis. JerF is the first known example of an enzyme that catalyses the formation of a non-aromatic, cyclic methylenolether. The enzyme was overexpressed in E. coli and the cell-free extracts were used in bioconversion experiments. Chemical synthesis gave access to a series of substrate surrogates that covered a broad structural space. Enzymatic assays revealed a broad substrate tolerance and high regioselectivity of JerF, which makes it an attractive candidate for an application in chemoenzymatic synthesis with particular usefulness for late stage application on 4-methoxy-5,6-dihydro-2H-pyran-2-one-containing natural products.
- Friedrich, Steffen,Hemmerling, Franziska,Lindner, Frederick,Warnke, Anna,Wunderlich, Johannes,Berkhan, Gesche,Hahn, Frank
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- A rapid and diverse construction of 6-substituted-5,6-dihydro-4-hydroxy-2- pyrones through double Reformatsky reaction
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A rapid and diverse synthesis of biologically important 6-substituted-5,6-dihydro-4-hydroxy-2-pyrones through a double Reformatsky reaction of aldehydes to δ-hydroxy-β-ketoesters followed by lactonization is described. Due to the high functional group tolerance and reaction site discrimination between aldehyde, nitrile, and ester groups in the substrate, the protocol can provide the dihydropyrones with bromo, nitro, carboxylic acid, and β-ketoester groups, which are suitable for the further derivatizations. Furthermore, the protocol has been successfully applied to the rapid total synthesis of naturally occurring Yangonin.
- Mineno, Masahiro,Sawai, Yasuhiro,Kanno, Kazuaki,Sawada, Naotaka,Mizufune, Hideya
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p. 10921 - 10926
(2014/01/06)
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- Synthesis of β-methoxyacrylate natural products based on box-Pd IIcatalyzed intermolecular methoxycarbonylation of alkynoles
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Bis(oxazoline)-palladium(II) catalyzed carbonylation of homopropargyl alcohols afforded acyclic methoxyacrylate 2 and 6-membered lactone 3a-k in good combined yield. In the case of propargyl alcohols, 5-membered lactones 3p, 3q, 16 were obtained in moderate yields. The one-pot synthesis of kawa lactones 3a, 3r, 3s and formal synthesis of dihydroxycystothiazole A and dihydroxycystothiazole C are presented. To elucidate the stereochemistry of (+)-annularin G and (-)-annularin H, the first asymmetric syntheses of these natural products were achieved.
- Motodate, Satoshi,Kobayashi, Takuya,Fujii, Mikio,Mochida, Tomoyuki,Kusakabe, Taichi,Katoh, Shigeki,Akita, Hiroyuki,Kato, Keisuke
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experimental part
p. 2221 - 2230
(2011/06/21)
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- Efficient enantioselective hetero-diels-alder reaction of brassard's diene with aliphatic aldehydes: A one-step synthesis of (R)-(+)-kavain and (S)-(+)-dihydrokavain
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An efficient catalytic asymmetric hetero-Diels-Alder reaction of Brassard's diene with aliphatic aldehydes was reported The catalyst which was generated from (R)-BINOL, Ti(i-PrO)4, and 4-picolyl chloride hydrochloride, promoted the reaction smoothly to afford the corresponding α, β-unsaturated λ-lactone derivatives in moderate-to-good yields (46-79%) with high enantioselectivities (up to 88% ee) Natural products (R)-(+)-kavain (70% ee, > 99% ee after single re crystallization) and (S)-(+)-dihydrokavain (84% ee) were also prepared in one step by using this methodology.
- Lin, Lili,Chen, Zhenling,Yang, Xu,Liu, Xiaohua,Feng, Xiaoming
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supporting information; scheme or table
p. 1311 - 1314
(2009/04/06)
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- Towards synthesis of kavalactone derivatives
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Kavalactone derivatives were synthesized using a Heck reaction of the 4-methoxy-6-vinyl-5,6-dihydropyran-2-one with aryl iodides. The Suzuki-Miyaura reaction of an aryl boronic acid and (Z)-4-methoxy-6-(2-iodovinyl)-5,6-dihydropyran-2-one has also been successfully used to produce both Z and E isomers of lactones.
- Amaral, Patrícia A.,Gouault, Nicolas,Roch, Myriam Le,Eifler-Lima, Vera L.,David, Michèle
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supporting information; experimental part
p. 6607 - 6609
(2009/04/06)
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- Versatile asymmetric synthesis of the kavalactones: First synthesis of (+)-kavain
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(Equation Presented) Three asymmetric pathways to the kavalactones have been developed. The first method is chiral auxiliary-based and utilizes aldol reactions of N-acetyl thiazolidinethiones followed by a malonate displacement/decarboxylation reaction. The second approach uses the asymmetric catalytic Mukaiyama additions of dienolate nucleophile equivalents developed by Carreira and Sato. Finally, tin-substituted intermediates, prepared by either of these routes, can serve as advanced general precursors of kavalactone derivatives via Pd(0)-catalyzed Stille couplings with aryl halides.
- Smith, Thomas E.,Djang, Mabel,Velander, Alan J.,Downey, C. Wade,Carroll, Kathleen A.,Van Alphen, Sophie
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p. 2317 - 2320
(2007/10/03)
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- Polymer-supported electron-rich diene for hetero Diels-Alder reactions
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A Brassard diene analogue was grafted on a modified Merrifield resin and used in a hetero Diels-Alder reaction with various aldehydes or ketones. The reaction gave access to 6-substituted 5,6-dihydropyrones (5a-u). This new immobilized electron-rich diene is more stable than the corresponding native diene, and is a versatile supported reagent.
- Pierres, Camille,George, Pascal,Van Hijfte, Luc,Ducep, Jean-Bernard,Hibert, Marcel,Mann, André
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p. 3645 - 3647
(2007/10/03)
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