A5070055512- Marine Sponges and Natural Products
- Chemical synthesis and alkaloids
- Advanced Synthetic Organic Chemistry
- Synthetic Organic Chemistry Methods
- Genomic variations and chromosomal abnormalities
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Microbial Natural Products and Biosynthesis
- Catalytic Alkyne Reactions
- Asymmetric Synthesis and Catalysis
- Synthesis and Reactions of Organic Compounds
- Acute Lymphoblastic Leukemia research
- Acute Myeloid Leukemia Research
- Retinoids in leukemia and cellular processes
- Immunotherapy and Immune Responses
- Psoriasis: Treatment and Pathogenesis
- Synthesis and Catalytic Reactions
- Chronic Lymphocytic Leukemia Research
- Carbohydrate Chemistry and Synthesis
- Quinazolinone synthesis and applications
- Synthesis and Characterization of Pyrroles
- Melanoma and MAPK Pathways
- Cytokine Signaling Pathways and Interactions
- Prenatal Screening and Diagnostics
Bristol-Myers Squibb (United States)
2014-2024
Max-Planck-Institut für Kohlenforschung
2013-2014
Max Planck Society
2013-2014
Scripps Research Institute
2004-2011
Michigan State University
1985-1999
Sparrow Hospital
1988
The true creator is necessity, who the mother of our invention. — Plato IUPAC defines chemoselectivity as "the preferential reaction a chemical reagent with one two or more different functional groups", definition that describes in rather understated terms single greatest obstacle to complex molecule synthesis. Indeed, efforts synthesize natural products often become case studies art and science chemoselective control, skill nature has practiced deftly for billions years but man yet master....
The dimeric pyrrole imidazole natural products are a growing class of alkaloids with exotic connectivity, unique topologies, high nitrogen content, and exciting bioactivities. This full account traces the evolution strategy that culminated in first total syntheses several members this family, including sceptrin, ageliferin, nagelamide E, nakamuric acid (and its methyl ester), oxysceptrin. Details on fascinating conversion sceptrin to which has been used produce gram quantities sensitive...
Orchestrated yet nonconsonant: The challenge posed by the "umpoled" 1,4-dioxygenation pattern characteristic for polyketide frame of amphidinolide F was mastered a late-stage ring-closing alkyne metathesis followed directed transannular hydration under aegis carbophilic π-acid catalyst. This concordant strategy enabled concise total synthesis this enticing marine natural product. As service to our authors and readers, journal provides supporting information supplied authors. Such materials...
Dimeric pyrrole–imidazole alkaloids represent a rich and topologically unique class of marine natural products. This full account will follow the progression efforts that culminated in enantioselective total syntheses most structurally ornate members this family: axinellamines, massadines, palau'amine. A bio-inspired approach capitalizing on pseudo-symmetry is recounted, delivering deschloro derivative product core. Next, synthesis chlorocyclopentane core featuring scalable, catalytic,...
Microwave-induced magic: There is a widely held conviction that the antiviral marine alkaloid ageliferin 1 arises biosynthetically from Diels–Alder reaction which, although possible, has yet to materialize in laboratory. A total synthesis of sceptrin now reported led new hypothesis for how and other dimeric pyrrole-imidazole alkaloids might be formed nature. Supporting information this article available on WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z53937_s.pdf or author. Please...
Abstract The marine natural products amphidinolide C ( 1 ) and F 4 differ in their side chains but share a common macrolide core with signature 1,4‐diketone substructure. This particular motif inspired synthesis plan predicating late‐stage formation of this non‐consonant (“umpoled”) pattern by platinum‐catalyzed transannular hydroalkoxylation cycloalkyne precursor. key intermediate was assembled from three building blocks 29 , 41 47 (or 65 )) Yamaguchi esterification, Stille cross‐coupling...
Gifted with novel chemical features and extraordinary biological activity, sceptrin has remained a prominent unanswered synthetic challenge since its characterization in 1981 by Faulkner Clardy. A concise practical solution to the myriad of challenges posed is reported this Communication. Thus, through sequence involving rearrangement an oxaquadricyclane, new method for chemo- regioselective halogenation, mild 2-aminoimidazole formation, careful choreography, (±)-sceptrin obtained minimum...
Magische Mikrowellen: Allgemein nimmt man an, dass die Biosynthese des antiviralen marinen Alkaloids Ageliferin (1) über eine Diels-Alder-Reaktion verläuft – experimentelle Bestätigung steht allerdings noch aus. Eine Totalsynthese von 1 ausgehend Sceptrin führte nun zu einer alternativen Hypothese für und anderen dimeren Pyrrol-Imidazol-Alkaloiden. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2004/z53937_s.pdf or from author....
Chemoselective by design: The first total synthesis of members the axinellamine/palau'amine/massadine class pyrrole–imidazole alkaloids features unconventional transformations on completely unprotected polyamino and hydroxylated substrates a new method for chemoselective oxidations in such settings. Supporting information this article is available WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z801138_s.pdf or from author. Please note: publisher not responsible content functionality...
Within reach: A 19-step route to 1,9-dideoxy-pre-axinellamine has been designed and executed. This key compound represents a hypothetical precursor an entire family of alkaloid natural products. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z705913_s.pdf or from author. Please note: The publisher not responsible content functionality any supporting supplied by authors. Any queries (other than missing content) should be...
Sceptrin, a natural compound produced by various marine sponges, was tested for its effect on cell motility. We report the first time that sceptrin inhibits motility in several cancer lines. The shows no toxicity at concentrations are double amount of required maximal inhibitory effect. Both random and factor-induced migration were impaired, suggesting targets central process machinery. Activity de novo synthesized indistinguishable from purified Agelas nakamurai, activity found to be, least...
Geglücktes Zusammenspiel: Das charakteristische "umgepolte" 1,4-Dioxygenierungsmuster im Polyketidgerüst von Amphidinolid F wurde durch eine Alkin-Ringschlussmetathese mit anschließender dirigierter transannularer Hydratisierung unter Anwendung eines carbophilen π-Säure-Katalysators späten Synthesestadium eingeführt. Auf dieser Strategie beruht kurze Totalsynthese des faszinierenden marinen Naturstoffs.
Absolutely without auxiliaries: The enantioselective syntheses of both enantiomers the dimeric pyrrole–imidazole alkaloids sceptrin and ageliferin have been achieved by a non-auxiliary-based route, which allows assignment absolute configuration natural ageliferin. "programming" oxaquadricyclane fragmentation leading to enantiopure tetrasubstituted cyclobutanes is crucial step in synthesis.
We have designed and developed novel selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay.
Chemoselektiv per Entwurf: Die erste Totalsynthese von Mitgliedern der Axinellamin-/Palau'amin-/Massadin-Klasse Pyrrolimidazol-Alkaloide besticht durch ungewöhnliche Transformationen an vollständig ungeschützten Polyamino- und hydroxylierten Substraten umfasst außerdem eine neue Methode für chemoselektive Oxidationen. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2008/z801138_s.pdf or from author. Please note: The publisher not...
C-terminal Src kinase (CSK) functions as a negative regulator of T cell activation through inhibitory phosphorylation LCK, so inhibitors CSK are interest potential immuno-oncology agents. Screening an internal inhibitor collection identified pyridazinone lead 1, and series modifications led to optimized compound 13. Compound 13 showed potent activity in biochemical cellular assays vitro demonstrated the ability increase proliferation induced by receptor signaling. gave extended exposure mice...
In Reichweite: Eine 19-stufige Synthese von 1,9-Didesoxypräaxinellamin wurde entworfen und ausgeführt. Diese Schlüsselverbindung ist eine hypothetische Vorstufe einer ganzen Familie Alkaloid-Naturstoffen.
Natürlich radikal: Die Mikrowellen-induzierte Umlagerung von Sceptrin in die Naturstoffe Ageliferin und Nagelamid E liefert Verbindungen etwa im gleichen Verhältnis, wie sie aus natürlichen Quellen isoliert werden. Nach Berechnungen verläuft Vinylcyclobutan-Cyclohexen-Umlagerung über Diradikalintermediate, es spricht alles dafür, dass diese auch an der Biosynthese beteiligt ist. Supporting information for this article is available on the WWW under...
Abstract Background: The bromodomains and extra-terminal domain (BET) proteins are a family of 4 adapter proteins, BRD2, BRD3, BRD4, BRDT, that bind to specific acetylated lysine residues on the histone tails chromatin recruit additional regulate gene transcription. c-MYC oncogene, which is amplified deregulated in 40% 70% all cancers, directly regulated by BET proteins. Preclinical studies provide strong rationale for pursuing transcriptional regulation via inhibition cancer treatment...
Ganz ohne Helfer: In nicht auf Auxiliaren basierenden enantioselektiven Synthesen wurden die beiden Enantiomere der dimeren Pyrrol-Imidazol-Alkaloide Sceptrin und Ageliferin erhalten, was Bestimmung absoluten Konfiguration von natürlichem ermöglichte. Die „Programmierung“ Oxaquadricyclan-Fragmentierung zu enantiomerenreinen tetrasubstituierten Cyclobutanen ist entscheidende Syntheseschritt. Supporting information for this article (detailed experimental procedures, copies of all spectral...
by the manufacturer.Both digested and undigested products were analysed electrophoresis on 2 per cent agarose gel followed staining with ethidium bromide.The normal mutant alleles should be easily distinguished since BstNI converts 88 bp fragment from a allele into 61 27 fragments.Figure 1 shows result of digestion PCR-amplified chorionic villus DNA, indicating that neonate is heterozygote, like mother.The possibility this heterozygous DNA was contaminating maternal extracted cultured villi...