- Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants
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Dioncoquinones belong to a family of natural naphthoquinone products of interest due to their promising anti-tumoral and anti-infective activities. In particular, dioncoquinones A (5) and B (6) have been shown to be highly active against Leishmania major and multiple myeloma cells without any significant toxicity toward normal blood cells. Their effective concentrations against multiple myeloma cell lines were similar to those of melphalan, a well known DNA-alkylating agent used in a standard therapy against B cell lymphoma and multiple myeloma. We report on the first total synthesis of the highly oxygenated anti-tumoral agent dioncoquinone B (6) and the isolation of its new, even higher-oxygenated analogs, dioncoquinones C (7), D (8), and E (9), from cell cultures of Triphyophyllum peltatum. In addition, several derivatives of these compounds were synthesized, including dioncoquinone C (7), and a small library of naphthoquinones was created. Furthermore, the first structure-activity relationship (SAR) study on this class of compounds was conducted, showing that each of the three hydroxy groups, at C-3, C-5, and C-6, is required for improved anti-tumoral activities and decreased cytotoxicities.
- Bringmann, Gerhard,Zhang, Guoliang,Hager, Anastasia,Moos, Michael,Irmer, Andreas,Bargou, Ralf,Chatterjee, Manik
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experimental part
p. 5778 - 5789
(2012/02/01)
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- γ-Silylated α,ss-unsaturated amides - Preparation by [1,5]-sigmatropic rearrangement and use as masked dienolate equivalents in carbonyl condensations
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The reaction of lithium dienolates derived from N,N-dialkylsenecioamides (1a-1c) with triorganosilyl electrophiles occurs initially at the oxygen atom predominantly, and is followed by an O → C silicon migration to afford the γ-silylated senecioamides (4a-4h). The γ-silylated senecioamide Z-4a undergoes fluoride-ion-mediated condensations with aromatic aldehydes to give kinetic α-(6) and thermodynamic γ-(5) condensation product patterns comparable to lithium dienolates. The TiCl4-mediated reactions with aldehydes gives a-products (6) in a highly syn-selective manner. Possible transitionstate models for the syn-selective condensations are discussed and a chair-like transition state featuring bidentate coordination to titanium (11) is proposed.
- Green, James R.,Alo, Babajide I.,Majewski, Marek,Snieckus, Victor
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experimental part
p. 745 - 759
(2009/12/04)
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- Palladium-Catalyzed Double and Single Carbonylation of Aryl Halides and Allylic Compounds
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After a brief introduction summarizing the author's previous work concerning the double carbonylation of aryl halides catalyzed by palladium complexes, newly found catalytic processes (1) for converting allylic formates and chlorides into β,γ-unsaturated acids and (2) the double carbonylation of allylic chlorides to β,γ-unsaturated α-keto amides are described.Mechanisms which reasonably account for the catalytic processes are proposed on the basis of studies concerning the properties of the organopalladium complexes.
- Yamamoto, Akio
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p. 433 - 446
(2007/10/02)
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- General Synthesis of Ketones from Carboxylic Esters and Carboxamides by Use of Mixed Organolithium-Magnesium Reagents: Syntheses of Artemisia Ketone
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The novel reagents formed by combination of Grignard reagents (RMgX) with lithium diisopropylamide (LDA) convert non-enolizable carboxylic esters or carboxamides into ketones which are protected from further reaction by their in situ conversion into enolates.These enolates can be trapped with electrophiles such as Me3SiCl and allyl bromide.The scope of this Grignard mono-addition is illustrated by two direct synthesis of artemisia ketone (14).
- Fehr, Charles,Galindo, Jose,Perret, Roland
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p. 1745 - 1752
(2007/10/02)
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