Synthesis of (+)-dynemicin A and analogs of wide structural variability: establishment of the absolute configuration of natural dynemicin A

Myers, Andrew G.; Fraley, Mark E.; Tom, Norma J.; Cohen, Scott B.; Madar, David J.

doi:10.1016/1074-5521(95)90078-0

Cited by 87 publications

(55 citation statements)

References 24 publications

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“…Several analogues were also made by using the same approach. In the following years, copious synthetic and SAR studies of enediyne analogues of the dynemicin core were performed by the groups of Schreiber,61a,61d Wender,63 Nicolaou,61b, 64 Isobe,65 Myers,62a, 66 Danishefsky,61g, 67 Maier,68 Magnus,69 and others 64a,64d, 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.…”

Section: Natural Product Derived Fragments In Drug Discoverymentioning

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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Section: Natural Product Derived Fragments In Drug Discoverymentioning

confidence: 99%

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

2016

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“…CNS-653 [37], were isolated in the cycloaromatized form. The discrete 10-membered enediynes consist of calicheamicin (CAL) from Micromonospora echinospora [26], esperamicin (ESP) from Actinomadura verrucosospora [15], dynemicin (DYN) from M. chersina [36], uncialamycin (UCM) from S. uncialis [9], and namenamicin and the shishijimicins from the marine ascidia Polysyncraton lithostrotum and Didemnum proliferum , respectively [33,39]. …”

Section: Introductionmentioning

confidence: 99%

Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery

Rudolf

Yan

Shen

2016

Journal of Industrial Microbiology and Biotechnology

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The enediynes are one of the most fascinating families of bacterial natural products given their unprecedented molecular architecture and extraordinary cytotoxicity. Enediynes are rare with only 11 structurally characterized members and four additional members isolated in their cycloaromatized form. Recent advances in DNA sequencing have resulted in an explosion of microbial genomes. A virtual survey of the GenBank and JGI genome databases revealed 87 enediyne biosynthetic gene clusters from 78 bacteria strains, implying enediynes are more common than previously thought. Here we report the construction and analysis of an enediyne genome neighborhood network (GNN) as a high-throughput approach to analyze secondary metabolite gene clusters. Analysis of the enediyne GNN facilitated rapid gene cluster annotation, revealed genetic trends in enediyne biosynthetic gene clusters resulting in a simple prediction scheme to determine 9- vs 10-membered enediyne gene clusters, and supported a genomic-based strain prioritization method for enediyne discovery.

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“…[183] Höhepunkte dieser Synthese (Schema 35) sind die stereoselektive Einführung der Endiin-Brücke, die Verwendung eines Chinonimins als Dienophil in einer regio-und stereoselektiven Diels-Alder-Reaktion und eine Reihe anderer, neuartiger Schritte zur Vervollständigung der Totalsynthese. Die zweite Totalsynthese von Dynemicin durch Danishefsky et al [184] .…”

Section: Dynemicin a (1995)unclassified

“…Die zweite Totalsynthese von Dynemicin durch Danishefsky et al [184] . [182] Schema 35. a) Strategische Bindungsbrüche und retrosynthetische Analyse von Dynemicin A; b) Totalsynthese (Myers et al, 1995). [183] Antitumoreigenschaften.…”

Section: Dynemicin a (1995)unclassified

Der Stand der Totalsynthese zu Beginn des 21. Jahrhunderts

Nicolaou¹,

et al. 2000

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Ein neues Jahrtausend hat begonnen – Grund genug, sich die Frage zu stellen, welchen Stand die Totalsynthese von Naturstoffen erreicht hat. Dieser Aufsatz möchte eine Antwort geben, indem er die Entwicklung dieser chemischen Disziplin, die Aspekte von exakter Wissenschaft und schöner Kunst in sich vereint, von Anbeginn bis in die heutige Zeit beschreibt; es wird geschildert, wie viel wir in der Wissenschaft der Totalsynthese schon erreicht haben, aber auch, dass dieses Forschungsgebiet den Kinderschuhen gerade erst entschlüpft.

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Synthesis of (+)-dynemicin A and analogs of wide structural variability: establishment of the absolute configuration of natural dynemicin A

Cited by 87 publications

References 24 publications

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

Genome neighborhood network reveals insights into enediyne biosynthesis and facilitates prediction and prioritization for discovery

Der Stand der Totalsynthese zu Beginn des 21. Jahrhunderts

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