The Synthesis of Deoxyfusapyrone. 2. Preparation of the Bis-Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety

Organ, Michael G.; Wang, Junquan

doi:10.1021/jo034371k

Cited by 26 publications

(17 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To set stage for the Horner-Wadsworth-Emmons (HWE) reaction, the phosphonate moiety was introduced with dimethyl methylphosphonate to give compound 34. The HWE reaction with para-methoxybenzyl (PMB)protected Roche aldehyde 35 [43] gave 36 in excellent yields and exclusively as the E isomer, as determined from the 1 H NMR spectra. After PMB deprotection of 36 with 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ), the liberated hydroxy function was methylated with a combination of iodomethane and silver(I) oxide.…”

Section: Synthesis Of the Eastern Fragmentsmentioning

confidence: 99%

See 1 more Smart Citation

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

et al. 2015

View full text Add to dashboard Cite

The natural products rhizopodin and bistramide belong to an elite class of highly potent actin binding agents. They show powerful antiproliferative activities against a range of tumor cell lines, with IC50 values in the low-nanomolar range. At the molecular level they disrupt the actin cytoskeleton by binding specifically to a few critical sites of G-actin, resulting in actin filament stabilization. The important biological properties of rhizopodin and bistramide, coupled with their unique and intriguing molecular architectures, render them attractive compounds for further development. However, this is severely hampered by the structural complexity of these metabolites. We initiated an interdisciplinary approach at the interface between molecular modeling, organic synthesis, and chemical biology to support further biological applications. We also wanted to expand structure-activity relationship studies with the goal of accessing simplified analogues with potent biological properties. We report computational analyses of actin-inhibitor interactions involving molecular docking, validated on known actin binding ligands, that show a close match between the crystal and modeled structures. Based on these results, the ligand shape was simplified, and more readily accessible rhizopodin-bistramide mimetics were designed. A flexible and modular strategy was applied for the synthesis of these compounds, enabling diverse access to dramatically simplified rhizopodin-bistramide hybrids. This novel analogue class was analyzed for its antiproliferative and actin binding properties.

show abstract

Section: Synthesis Of the Eastern Fragmentsmentioning

confidence: 99%

“…Stirring was continued for 1 h at À78 8C. Afterward, aldehyde 35 [43] (163 mg, 0.783 mmol, 1.0 equiv) was added over a period of 20 min. The reaction mixture was stirred for 2 h at À78 8C and was then slowly allowed to warm to RT.…”

Section: Synthesis Of the Middle Fragmentsmentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

et al. 2015

View full text Add to dashboard Cite

show abstract

“…A similar procedure to that of Organ and co-workers was utilized. 7 A solution of 3 (4.5 g, 21.6 mmol) in dry acetone was added sodium iodide (7.9, 52.8 mmol). The reaction mixture was heated at gentle reflux for 4 h. The mixture was allowed to cool to room temperature.…”

Section: Synthesis Of 1-iodo-[11-d 2 ] Octane (4)mentioning

confidence: 99%

Site‐specific ²H‐labeled oleic acid and derived esters for use as tracers of ethyl oleate metabolism in honey bees

Chen

Plettner

2011

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

The inventory of labeled fatty acids and protocols for their syntheses are constantly increasing, but site-specific labeled precursors in biosynthetic studies are still needed. Ethyl oleate (EO) is an important primer pheromone in honeybees, which is responsible for the regulation of behavioral maturation. During our biosynthetic studies on EO, a site-specific labeled oleic acid precursor was required. In this report, a synthetic route adaptable to the preparation of [9,10,11,11-D 4 ] oleic acid and its derived esters for use as tracers of EO metabolism in honey bees is presented.

show abstract

“…[54] Das Spiro[5.5]ketal bildet ein starres molekulares Gerüst, das in zahlreichen komplexen Naturstoffen mit breitem biologischem Aktivitätsprofil vorliegt (Schema 14). Zum Beispiel enthalten die außerordentlich wirksamen tubulinpolymerisationsinhibierenden Spongistatine, [55] die Proteinphosphatasehemmer Okadasäure [56] und Tautomycin [57] und der HIV-1-Proteaseinhibitor Integramycin das SpiroacetalElement. Interessanterweise zeigen strukturell vereinfachte Derivate, die aber noch die charakteristische SpiroketalGruppierung aufweisen, oft eine vergleichbare biologische Aktivität wie die natürliche Stammverbindung.…”

Section: Verbindungsbibliotheken Mit Einem Spiroacetal Als Strukturmotivunclassified

Die Synthese von naturstoffinspirierten Verbindungsbibliotheken

Kumar

Waldmann

2009

Angewandte Chemie

View full text Add to dashboard Cite

Der Natur abgeschaut: Die Entwicklung vielstufiger stereoselektiver Synthesen eröffnet den Zugang zu naturstoffinspirierten Verbindungsbibliotheken mit carbo‐, oxa‐ und azacyclischen Gerüststrukturen, die vielversprechende Quellen für neue Reagentien in der medizinischen Chemie und der chemischen Biologie sind. Das Bild zeigt eine Sammlung von naturstoffinspirierten Molekülen (blau) mit ihren zugrundeliegenden Naturstoffen (gelb).magnified imageNaturstoffe und ihre Derivate und Analoga gehören zu den wichtigsten Quellen neuer Wirkstoffkandidaten und Reagentien für die chemische Biologie und medizinische Chemie. Hieraus leitet sich ein großer Bedarf an effizienten Synthesemethoden ab, die einen Zugang zu naturstoffabgeleiteten oder ‐inspirierten Verbindungsbibliotheken ermöglichen. Um solche Verfahren entwickeln und anwenden zu können, ist es erforderlich, die vielstufigen stereoselektiven Synthesemethoden, wie sie für Naturstoffsynthesen charakteristisch sind, auf die Verfahrensweisen beim Aufbau von Verbindungsbibliotheken zu übertragen und entsprechend anzupassen. Neue Entwicklungen bei der Synthese naturstoffinspirierter Bibliotheken aus carbocyclischen und heterocyclischen Gerüststrukturen zeigen klar auf, dass dieses Ziel erreicht werden kann. Die bereits erzielten Fortschritte haben den Weg für die Einbeziehung naturstoffinspirierter Verbindungsbibliotheken in die medizinische Chemie und die biochemische Forschung geebnet.

show abstract

The Synthesis of Deoxyfusapyrone. 2. Preparation of the Bis-Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety

Cited by 26 publications

References 21 publications

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

Site‐specific ²H‐labeled oleic acid and derived esters for use as tracers of ethyl oleate metabolism in honey bees

Die Synthese von naturstoffinspirierten Verbindungsbibliotheken

Contact Info

Product

Resources

About

The Synthesis of Deoxyfusapyrone. 2. Preparation of the Bis-Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety

Cited by 26 publications

References 21 publications

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

Design, Synthesis, and Biological Evaluation of Simplified Side Chain Hybrids of the Potent Actin Binding Polyketides Rhizopodin and Bistramide

Site‐specific 2H‐labeled oleic acid and derived esters for use as tracers of ethyl oleate metabolism in honey bees

Die Synthese von naturstoffinspirierten Verbindungsbibliotheken

Contact Info

Product

Resources

About

Site‐specific ²H‐labeled oleic acid and derived esters for use as tracers of ethyl oleate metabolism in honey bees