The application of vinylogous iminium salt derivatives to an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B

Gupton, John T.; Miller, Robert B.; Krumpe, Keith E.; Clough, Stuart C.; Banner, Edith J.; Kanters, R. P. F.; Du, Karen; Keertikar, Kartik M.; Lauerman, Nicholas E.; Solano, John M.; Adams, Bret R.; Callahan, Daniel W.; Little, Barrett A.; Scharf, Austin B.; Sikorski, James A.

doi:10.1016/j.tet.2004.12.015

Cited by 29 publications

(14 citation statements)

References 11 publications

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“…This material was identical to the product obtained by method A as determined by 1 H NMR and TLC comparison. Formyl-3-(4-bromophenyl) 4.41 (q, J = 6.9 Hz, 2H) and 1.42 (t, J = 6.9 Hz, 3H); 13 N-Methyl-2-formyl-3-(4-methylphenylpyrrole) …”

Section: Methods Bmentioning

confidence: 99%

The application of vinylogous iminium salt derivatives and microwave accelerated Vilsmeier–Haack reactions to efficient relay syntheses of the polycitone and storniamide natural products

et al. 2008

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Studies directed at the synthesis of polycitone and storniamide natural products via vinylogous iminium salts and microwave accelerated Vilsmeier-Haack formylations are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 2,3,4-trisubstituted pyrrole from a vinamidinium salt or vinamidinium salt derivative followed by formylation at the 5-position of the pyrrole. Subsequent transformations of the selectively formylated pyrroles lead to efficient and regiocontrolled relay syntheses of the respective pyrrole containing natural products.

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Section: Methods Bmentioning

confidence: 99%

The application of vinylogous iminium salt derivatives and microwave accelerated Vilsmeier–Haack reactions to efficient relay syntheses of the polycitone and storniamide natural products

et al. 2008

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“…Because we have focused on a series of eighteen compounds with IC 50 s ranging over more than three orders of magnitude (see Table 1), we performed detailed docking studies with GOLD [21,22] followed by free energy scoring using the HINT protocol [17,27] to assess the binding modes. Without added constraints GOLD was found to reliably re-dock the crystallographic DAMA-colchicine ligand (RMSD = 0.76 Å) that was then used as the reference for all other docking experiments.…”

Section: The Colchicine Binding Sitementioning

confidence: 99%

“…The synthetic methods used to prepare the highly functionalized pyrroles and related derivatives depicted in Scheme I can be found in previously reported work [19][20][21][22][23].…”

Section: Synthesis Of Pyrrole Compoundsmentioning

confidence: 99%

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

Tripathi

Fornabaio

Kellogg

et al. 2008

Bioorganic & Medicinal Chemistry

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Compounds that bind at the colchicine site of tubulin have drawn considerable attention with studies indicating that these agents suppress microtubule dynamics and inhibit tubulin polymerization. Data for eighteen polysubstituted pyrrole compounds are reported, including antiproliferative activity against human MDA-MB-435 cells and calculated free energies of binding following docking the compounds into models of αβ-tubulin. These docking calculations coupled with HINT interaction analyses are able to represent the complex structures and the binding modes of inhibitors such that calculated and measured free energies of binding correlate with an r 2 of 0.76. Structural analysis of the binding pocket identifies important intermolecular contacts that mediate binding. As seen experimentally, the complex with JG-03-14 (3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester) is the most stable. These results illuminate the binding process and should be valuable in the design of new pyrrole-based colchicine site inhibitors as these compounds have very accessible syntheses.

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“…A partial example of our previously, published 4 approach to the synthesis of the Polycitones is presented in Scheme 1 and involves the formation of a symmetrical vinamidinium salt ( 4 ), followed by the reaction of this salt with the appropriate α-aminocarbonyl compound (5 ) such that a 2,4-disubstituted pyrrole ( 6 ) is generated in good yield. This material ( 6 ) can be further functionalized to an intermediate ( 7 ) reported by Steglich 5 and coworkers in the first reported synthesis of the Polycitones.…”

Section: Introductionmentioning

confidence: 99%

Formyl group activation of a bromopyrrole ester in Suzuki cross-coupling reactions: application to a formal synthesis of Polycitone A and B and Polycitrin A

et al. 2014

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A new pyrrole building block is described, which allows for the regiospecific synthesis of 2,3,5-trisubstituted pyrroles and 2,3,4,5- tetrasubstituted pyrroles. Optimization studies are presented for the preparation of the pyrrole building block along with the evaluation of various cross-coupling conditions and cross-coupling agents. A short, formal synthesis of the natural products Polycitone A, Polycitone B and Polycitrin A from the pyrrole building block is also described.

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The application of vinylogous iminium salt derivatives to an efficient relay synthesis of the pyrrole containing alkaloids polycitone A and B

Cited by 29 publications

References 11 publications

The application of vinylogous iminium salt derivatives and microwave accelerated Vilsmeier–Haack reactions to efficient relay syntheses of the polycitone and storniamide natural products

The application of vinylogous iminium salt derivatives and microwave accelerated Vilsmeier–Haack reactions to efficient relay syntheses of the polycitone and storniamide natural products

Docking and hydropathic scoring of polysubstituted pyrrole compounds with antitubulin activity

Formyl group activation of a bromopyrrole ester in Suzuki cross-coupling reactions: application to a formal synthesis of Polycitone A and B and Polycitrin A

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