477883-68-4Relevant academic research and scientific papers
Organometallic routes to 2,5-dihydroxy-3-(indol-3-yl)benzoquinones. Synthesis of demethylasterriquinone B4
Pirrung, Michael C.,Fujita, Koichi,Park, Kaapjoo
, p. 2537 - 2542 (2007/10/03)
(Figure Presented) A method has been developed to sequentially add indole-3-mercurials to dichlorinated quinones using palladium catalysis. These reactions can be used in the modular assembly of bis(indol-3-yl)-benzoquinones, a significant natural product family.
Methyl scanning: Total synthesis of demethylasterriquinone B1 and derivatives for identification of sites of interaction with and isolation of its receptor(s)
Pirrung, Michael C.,Liu, Yufa,Deng, Liu,Halstead, Diana K.,Li, Zhitao,May, John F.,Wedel, Michael,Austin, Darrell A.,Webster, Nicholas J. G.
, p. 4609 - 4624 (2007/10/03)
The principle of methyl scanning is proposed for determination of the sites of interaction between biologically active small molecules and their macromolecular target(s). It involves the systematic preparation of a family of methylated derivatives of a co
Synthesis of 2,5-dihydroxy-3-(indol-3-yl)benzoquinones by acid-catalyzed condensation of indoles with 2,5-dichlorobenzoquinone
Pirrung, Michael C.,Deng, Liu,Li, Zhitao,Park, Kaapjoo
, p. 8374 - 8388 (2007/10/03)
Three methods for the conjugate addition of indoles to 2,5-dichlorobenzoquinone have been developed. A wide variety of indoles substituted with halogen, alkyl, alkoxy, and aryl groups participate in anaerobic condensation reactions promoted by HCl, H2SO4, or CH3CO2H. The hydroquinone product is partially oxidized by excess dichlorobenzoquinone and fully converted to the 2,5-dichloro-3-(indol-3-yl)benzoquinone targets by DDQ or Ag2CO3 oxidation. 2,5-Dihydroxy- 3-(indol-3-yl)benzoquinones can be obtained from the dichlorides by alkaline hydrolysis. The rotational characteristics of the biaryl bond created in these reactions have been examined by theoretical and spectroscopic methods.
Total syntheses of demethylasterriquinone B1, an orally active insulin mimetic, and demethylasterriquinone A1.
Pirrung, Michael C,Li, Zhitao,Park, Kaapjoo,Zhu, Jin
, p. 7919 - 7926 (2007/10/03)
Two total syntheses of the unsymmetrical bis-indolylquinone natural product demethylasterriquinone B1 (also known as L-783,281) have been accomplished. The first exploits a known base-promoted condensation of indoles with bromanil, which stops at monoaddition using the sterically hindered 2-isoprenylindole. This permits addition of the second indole, 7-prenylindole, which gives both meta- and para-substituted bis-indolylquinone products. This regiochemical control problem was solved by extension of a method we recently developed for acid-promoted addition of indoles to 2,5-dichlorobenzoquinone. Under our original mineral acid conditions, reaction of 2-isoprenylindole with dichlorobenzoquinone fails, but it succeeds with 3-bromo-2,5-dichlorobenzoquinone using acetic acid as the promoter. The regiochemistry established in such selectively bromine-substituted quinones can be exploited in Stille couplings. As a model system, the synthesis of demethylasterriquinone A1 was accomplished using as the key step a Stille coupling of a 2,5-dibromobenzoquinone with an (N-isoprenylindol-3-yl)tin, producing the para-substituted bis-indolylquinone exclusively. Use of a (7-prenylindole)tin in coupling with a bromo-2,5-dichloro-4-indolylbenzoquinone gives the demethylasterriquinone B1 precursor. The dihaloquinone products of these indole/quinone coupling processes can be hydrolyzed to the dihydroxyquinone natural products. Demethylasterriquinone B1 is of high recent interest as a small molecule insulin mimetic with oral anti-diabetic activity in mice.
