Cross-coupling approach towards dynemicin analogs without the nitrogen

Boße, Folkert; Tunoori, Ashok Rao; Maier, Martin E.

doi:10.1016/s0040-4020(97)00616-9

Cited by 16 publications

(5 citation statements)

References 42 publications

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“…For example, with Molt-4 leukemia cells 94b has arylboronic acid. [48,49] These results underscore the import-an IC 50 of 9·10 Ϫ5 . Electrochemical studies and also the chemical experiment led us to suspect that the oxidation might produce aryl dimers.…”

Section: Analogs Without the Nitrogen Heterocyclementioning

confidence: 82%

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Design and Synthesis of Dynemicin Analogs

Maier¹,

Boße

Niestroj

1999

Eur. J. Org. Chem.

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Dynemicin A is a member of the family of enediyne natural products. It is unique in that it combines a ten‐membered enediyne with an anthraquinone substructure. These features stimulated the development of synthetic approaches to the natural product itself and of analogs thereof. This review summarizes the total syntheses of dynemicin A. In addition, an overview of the known analogs is presented. The analogs can be classified according to the designed trigger mechanism. Most of the analogs contain a removable carbamate on the nitrogen atom. Others are quite similar to the natural lead in that they contain a quinone substructure, which upon reduction causes opening of the oxirane ring. In addition, there are analogs that contain an aromatic sector, the enediyne, and the oxirane ring but lack the nitrogen heterocycle. In these compounds the aryl ring assumes a different conformation from that in dynemicin A. Many of the simplified analogs proved to be quite active in vitro as well in vivo against murine tumor models. A highlight is compound 30 which is much more active than dynemicin A itself. However, looking at all analogs there is no clear‐cut correlation between the DNA‐cleaving ability at neutral pH and the in vitro results. From this one might conclude that there are possibly two mechanisms for antitumor activity. One involves diradical formation whereas the other might be due to a ligand‐receptor interaction.

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Section: Analogs Without the Nitrogen Heterocyclementioning

confidence: 82%

“…Using various tumor cell lines, nane 87 with the iodoenone 88 on a 10-g scale. [50] The iodoenone 88 was obtained from the corresponding enone by such as HT15, CCRF-CEM, and HeLa cells an IC 50 value of about 1.2·10 Ϫ4  was found. This points to the fact that reaction with trimethylsilyl azide and iodine.…”

Section: Analogs Without the Nitrogen Heterocyclementioning

confidence: 97%

Design and Synthesis of Dynemicin Analogs

Maier¹,

Boße

Niestroj

1999

Eur. J. Org. Chem.

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“…[62] In total, this route was completed in 26 steps in 0.3 %yield and employed an exo-selective Diels-Alder reaction as the key step.S everal analogues were also made by using the same approach. In the following years,c opious synthetic and SAR studies of enediyne analogues of the dynemicin core were performed by the groups of Schreiber, [61a,d] Wender, [63] Nicolaou, [61b, 64] Isobe, [65] Myers, [62a, 66] Danishefsky, [61g, 67] Maier, [68] Magnus, [69] and others. [64a,d,70] These studies probed the effects of triggering groups or initiators on the nitrogen atom or aryl ring, which could be activated under basic or photochemical conditions that could be mimicked by intracellular processes.T ethering devices were also investigated to aid target delivery,a sw ere deactivating groups that would modulate enediyne activity,aswell as detection devices that would facilitate mechanistic studies.…”

Section: From Dynemicin At Oadynemicin Analoguementioning

confidence: 99%

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

2016

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Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

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“…4,10-Bis(3-((tert-butyldimethylsilyl)oxy)phenyl)anthanthrone (5). A dry flask under nitrogen was charged with (3bromophenoxy)-tert-butyldimethylsilane 35 (928 mg, 3.23 mmol) and anhydrous THF (7 mL), and the flask was cooled at −78 °C using a dry ice/acetone bath followed by the dropwise addition of n-BuLi (2.5 M in hexanes, 1.36 mL, 3.39 mmol). After 10 min, tributyltin chloride (1.10 g, 0.92 mL, 3.39 mmol) was added in one portion, and the reaction mixture was gradually warmed at 0 °C over 5 h. A separate flask was charged with 4,10-dibromoanthanthrone (500 mg, 1.07 mmol), dichlorobis(triphenylphosphine)palladium(II) (38 mg, 0.054 mmol), and o-dichlorobenzene (20 mL) and deaerated using a continuous flow of nitrogen for 10 min.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Superextended Tetrathiafulvalene: Synthesis, Optoelectronic Properties, Fullerenes Complexation, and Photooxidation Study

Giguère

Morin

2015

J. Org. Chem.

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Superextended tetrathiafulvalene compounds were prepared by the substitution of gem-dichlorovinylene with 1,2-benzenedithiol. This strategy allowed for the efficient synthesis of a highly π-extended 9,10-bis(benzo-1,3-dithiol-2-ylidene)-9,10-dihydroanthracene (sExTTF) moiety, which exhibits an intense light absorption in the visible spectrum and a reversible oxidation process. A macrocyclic host for fullerenes containing two sExTTF units was synthesized. Complexation studies revealed that fullerenes promote the photooxidation of the 1,3-dithiolylidene bond. This grants new insights into the nature of the low-energy band that appeared in several reports on fullerene complexation with hosts containing the 1,3-dithiolylidene moiety.

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Cross-coupling approach towards dynemicin analogs without the nitrogen

Cited by 16 publications

References 42 publications

Design and Synthesis of Dynemicin Analogs

Design and Synthesis of Dynemicin Analogs

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

Superextended Tetrathiafulvalene: Synthesis, Optoelectronic Properties, Fullerenes Complexation, and Photooxidation Study

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