Robert J. Aversa

The Scripps Research Institute, La Jolla, CA, United States

Are you Robert J. Aversa?

Claim your profile

Publications (13)79.74 Total impact

  • K. C. Nicolaou, Robert J. Aversa
    ChemInform 09/2011; 42(38).
  • ChemInform 04/2011; 42(14).
  • Source
    K C Nicolaou, Robert J Aversa
    [Show abstract] [Hide abstract]
    ABSTRACT: Maitotoxin holds a special place in the annals of natural products chemistry as the largest and most toxic secondary metabolite known to date. Its fascinating, ladder-like, polyether molecular structure and diverse spectrum of biological activities elicited keen interest from chemists and biologists who recognized its uniqueness and potential as a probe and inspiration for research in chemistry and biology. Synthetic studies in the area benefited from methodologies and strategies that were developed as part of chemical synthesis programs directed toward the total synthesis of some of the less complex members of the polyether marine biotoxin class, of which maitotoxin is the flagship. This account focuses on progress made in the authors' laboratories in the synthesis of large maitotoxin domains with emphasis on methodology development, strategy design, and structural comparisons of the synthesized molecules with the corresponding regions of the natural product. The article concludes with an overview of maitotoxin's biological profile and future perspectives.
    Israel Journal of Chemistry 04/2011; 51(3-4):359-377. · 3.03 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A devised biomimetic strategy toward the C′D′E′F′ domain (6) of maitotoxin (1) led to hydroxy triepoxide 8 as a postulated polyepoxide precursor. However, all attempts to induce the desired cascade to form the targeted compound through a zip-type reaction under neutral or acidic conditions failed, prompting adoption of a linear stepwise approach to 6. The successful synthetic strategy for the synthesis of the C′D′E′F′ domain of maitotoxin commenced from furfuryl alcohol (11), proceeded through F′ ring building block 15, and involved two regio- and stereoselective intramolecular hydroxy epoxide openings and a stereoselective SmI2-mediated ring closure to forge rings C′, E′, and D′, respectively. 13C NMR spectroscopic analysis of the synthesized domain (6) and comparisons with previous results confirmed the original structural assignment of this region of maitotoxin. X-ray crystallographic analysis of 6 provided unambiguous proof of its structure.
    Journal of the American Chemical Society 12/2010; 133(2):214–219. · 10.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A devised biomimetic strategy toward the C'D'E'F' domain (6) of maitotoxin (1) led to hydroxy triepoxide 8 as a postulated polyepoxide precursor. However, all attempts to induce the desired cascade to form the targeted compound through a zip-type reaction under neutral or acidic conditions failed, prompting adoption of a linear stepwise approach to 6. The successful synthetic strategy for the synthesis of the C'D'E'F' domain of maitotoxin commenced from furfuryl alcohol (11), proceeded through F' ring building block 15, and involved two regio- and stereoselective intramolecular hydroxy epoxide openings and a stereoselective SmI(2)-mediated ring closure to forge rings C', E', and D', respectively. (13)C NMR spectroscopic analysis of the synthesized domain (6) and comparisons with previous results confirmed the original structural assignment of this region of maitotoxin. X-ray crystallographic analysis of 6 provided unambiguous proof of its structure.
    Journal of the American Chemical Society 12/2010; · 10.68 Impact Factor
  • Source
    K C Nicolaou, Robert J Aversa, Jian Jin, Fatima Rivas
    [Show abstract] [Hide abstract]
    ABSTRACT: Maitotoxin (1) continues to fascinate scientists not only because of its size and potent neurotoxicity but also due to its molecular architecture. To provide further support for its structure and facilitate fragment-based biological studies, we developed an efficient chemical synthesis of the ABCDEFG segment 3 of maitotoxin. (13)C NMR chemical shift comparisons of synthetic 3 with the corresponding values for the same carbons of maitotoxin revealed a close match, providing compelling evidence for the correctness of the originally assigned structure to this polycyclic system of the natural product. The synthetic strategy for the synthesis of 3 relied heavily on our previously developed furan-based technology involving sequential Noyori asymmetric reduction and Achmatowicz rearrangement for the construction of the required tetrahydropyran building blocks, and employed a B-alkyl Suzuki coupling and a Horner-Wadsworth-Emmons olefination to accomplish their assembly and elaboration to the final target molecule.
    Journal of the American Chemical Society 04/2010; 132(19):6855-61. · 10.68 Impact Factor
  • Angewandte Chemie International Edition 09/2008; 47(38). · 11.34 Impact Factor
  • Angewandte Chemie 09/2008; 120(38).
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die beispiellose Struktur des marinen Naturstoffs Brevetoxin B wurde 1981 von den Arbeitsgruppen um Nakanishi und Clardy aufgeklärt. Das leiterförmige Molekülgerüst dieses kondensierten Polyethers, die starke Toxizität und der faszinierende Wirkmechanismus durch Angriff am spannungsgesteuerten Natriumkanal sorgten für Aufmerksamkeit. Syntheseversuche führten zur Entwicklung zahlreicher neuer Methoden und Strategien zum Aufbau von Etherringen und wurden schließlich durch die Totalsynthesen von Brevetoxin B und einigen verwandten, ähnlich anspruchsvollen Zielverbindungen gekrönt. Unter den marinen Polyethern nimmt Maitotoxin als kompliziertester und giftigster Vertreter eine Sonderstellung ein; die Verbindung ist der größte bekannte nichtpolymere Naturstoff überhaupt. Dieser Aufsatz beginnt mit einer kurzen Geschichte zur Isolierung der Biotoxine und beleuchtet ihre biologischen Eigenschaften und Wirkmechanismen. Dann werden Syntheseversuche beschrieben, wobei besonders neue Methoden berücksichtigt werden, die im Laufe dieser Studien entwickelt wurden. Den Abschluss bilden eine Diskussion der noch nicht abgeschlossenen Totalsynthese von Maitotoxin sowie ein Ausblick auf die weitere Entwicklung des Forschungsgebiets.
    Angewandte Chemie 09/2008; 120(38):7292 - 7335.
  • [Show abstract] [Hide abstract]
    ABSTRACT: As the largest secondary metabolite to be discovered as of yet, the polyether marine neurotoxin maitotoxin constitutes a major structural and synthetic challenge. After its originally proposed structure ( 1) had been questioned on the basis of biosynthetic considerations, we provided computational and experimental support for structure 1. In an effort to provide stronger experimental evidence of the molecular architecture of maitotoxin, its GHIJKLMNO ring system 3 was synthesized. The (13)C NMR chemical shifts of synthetic 3 matched closely those corresponding to the same domain of the natural product providing strong evidence for the correctness of the originally proposed structure of maitotoxin ( 1).
    Journal of the American Chemical Society 07/2008; 130(23):7466-76. · 10.68 Impact Factor
  • Source
    K C Nicolaou, Michael O Frederick, Robert J Aversa
    [Show abstract] [Hide abstract]
    ABSTRACT: The unprecedented structure of the marine natural product brevetoxin B was elucidated by the research group of Nakanishi and Clardy in 1981. The ladderlike molecular architecture of this fused polyether molecule, its potent toxicity, and fascinating voltage-sensitive sodium channel based mechanism of action immediately captured the imagination of synthetic chemists. Synthetic endeavors resulted in numerous new methods and strategies for the construction of cyclic ethers, and culminated in several impressive total syntheses of this molecule and some of its equally challenging siblings. Of the marine polyethers, maitotoxin is not only the most complex and most toxic of the class, but is also the largest nonpolymeric natural product known to date. This Review begins with a brief history of the isolation of these biotoxins and highlights their biological properties and mechanism of action. Chemical syntheses are then described, with particular emphasis on new methods developed and applied to the total syntheses. The Review ends with a discussion of the, as yet unfinished, story of maitotoxin, and projects into the future of this area of research.
    Angewandte Chemie International Edition 02/2008; 47(38):7182-225. · 11.34 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2008; 39(48).
  • Angewandte Chemie International Edition 02/2007; 46(46):8875-9. · 11.34 Impact Factor

Publication Stats

64 Citations
79.74 Total Impact Points

Institutions

  • 2011
    • The Scripps Research Institute
      • Skaggs Institute for Chemical Biology
      La Jolla, CA, United States
  • 2008
    • University of California, San Diego
      • Department of Chemistry and Biochemistry
      San Diego, CA, United States