Total Synthesis and Confirmation of the Revised Structures of Azaspiracid‐2 and Azaspiracid‐3

Nicolaou, K. C.; Frederick, Michael O.; Petrović, Goran; Cole, Kevin P.; Loizidou, Eriketi Z.

doi:10.1002/anie.200600295

Cited by 70 publications

(24 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Structural motifs misassigned on the basis of NOEs include epoxides (calafianin, 96–98 symbiodinolide 99, 100 ), cyclopropyl rings (clavosolide A, 101, 102 laurentristich-4-ol 103, 104 ), bridges (vannusals A and B 105–107 ), fused ring junctions (itomanallene A, 108, 109 asperdimin, 110, 111 aplysiallene 112, 113 ), polyethers (aplysiol B, 114, 115 azaspiracids 116–119 ), vicinal polyols (amphidinolide H2, 120, 121 hyrtiosterol, 122, 123 pericosine A 124, 125 ), sugars (callipeltoside C; 126, 127 fusapyrone and deoxyfusapyrone, 128, 129 Table 6) and macrolides (palmerolide A, 130–132 neopeltolide 133, 134 ).…”

Section: Sources Of Natural Product Structural Misassignmentsmentioning

confidence: 99%

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Suyama

Gerwick

McPhail

2011

Bioorganic & Medicinal Chemistry

164

175

View full text Add to dashboard Cite

The structural assignment of new natural product molecules supports research in a multitude of disciplines that may lead to new therapeutic agents and or new understanding of disease biology. However, reports of numerous structural revisions, even of recently elucidated natural products, inspired the present survey of techniques used in structural misassignments and subsequent revisions in the context of constitutional or configurational errors. Given the comparatively recent development of marine natural products chemistry, coincident with the modern spectroscopy, it is of interest to consider the relative roles of spectroscopy and chemical synthesis in the structure elucidation and revision of those marine natural products which were initially misassigned. Thus, a tabulated review of all marine natural product structural revisions from 2005 to 2010 is organized according to structural motif revised. Misassignments of constitution are more frequent than perhaps anticipated by reliance on HMBC and other advanced NMR experiments, especially considering the full complement of all natural products. However, these techniques also feature prominently in structural revisions, specifically of marine natural products. Nevertheless, as is the case for revision of relative and absolute configuration, total synthesis is a proven partner for marine, as well as terrestrial, natural products structure elucidation. It also becomes apparent that considerable ‘detective work’ remains in structure elucidation, in spite of the spectacular advances in spectroscopic techniques.

show abstract

Section: Sources Of Natural Product Structural Misassignmentsmentioning

confidence: 99%

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Suyama

Gerwick

McPhail

2011

Bioorganic & Medicinal Chemistry

164

175

View full text Add to dashboard Cite

show abstract

“…AZA-2, used for immobilization on the microsphere surface, was synthesized by Nicolaou and co-workers as previously described [5,7,9,26,27]. N -hydroxysuccinimide (NHS), boric acid, bovine serum albumin (BSA), Tween-20, dimethyl sulfoxide (DMSO) and sodium tetraborate decahydrate were obtained from Sigma-Aldrich (Madrid, Spain), and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) was purchased from Pierce (Rockford, Illinois).…”

Section: Methodsmentioning

confidence: 99%

Microsphere-based immunoassay for the detection of azaspiracids

Rodríguez

Vilariño

Louzao

et al. 2014

Analytical Biochemistry

Self Cite

View full text Add to dashboard Cite

Azaspiracids (AZAs) are a group of lipophilic toxins discovered in mussels from Ireland in 1995 following a human poisoning incident. Nowadays the regulatory limit for AZAs in many countries is set at 160 Fg of azaspiracid equivalents per kg of shellfish meat. In this work a microsphere-based immunoassay has been developed for the detection of AZAs using a Luminex system. This method is based on the competition between AZA-2 immobilized onto the surface of microspheres and free AZAs for the interaction with a monoclonal anti-azaspiracid antibody (mAb 8F4). In this inhibition immunoassay the amount of mAb 8F4 bound to AZA-2-microspheres was quantified using a phycoerythrin-labeled anti-mouse antibody, and the fluorescence was measured with a Luminex analyzer. Simple acetate/methanol or methanol extractions yielded final extracts with no matrix interferences and adequate recovery rates of 86.5% and 75.8%, respectively. In summary, this work presents, a sensitive and easily performed screening method capable of detecting AZAs at concentrations below the range of the European regulatory limit using a microsphere/flow cytometry system.

show abstract

“…This signaled the beginning of a third phase of the project that dealt with further analytical, biological, and chemical investigations of azaspiracid-1 and its siblings. These investigations culminated in second and improved generation total syntheses of azaspiracid-1, -2, and -3, 185 and several insights regarding the chemical biology and mode of action of this class of marine neurotoxins. 186 The total synthesis of ent -azaspiracid-1 has also been achieved.…”

Section: Highlights Of Contributions From the Author’s Laboratoriesmentioning

confidence: 99%

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

et al. 2012

Self Cite

View full text Add to dashboard Cite

The advent of organic synthesis and the understanding of the molecule as they occurred in the nineteenth century and were refined in the twentieth century constitute two of the most profound scientific developments of all time. These discoveries set in motion a revolution that shaped the landscape of the molecular sciences and changed the world. Organic synthesis played a major role in this revolution through its ability to construct the molecules of the living world and others like them whose primary element is carbon. Although the early beginnings of organic synthesis came about serendipitously, organic chemists quickly recognized its potential and moved decisively to advance and exploit it in myriad ways for the benefit of mankind. Indeed, from the early days of the synthesis of urea and the construction of the first carbon-carbon bond, the art of organic synthesis improved to impressively high levels of sophistication. Through its practice, today chemists can synthesize organic molecules—natural and designed—of all types of structural motifs and for all intents and purposes. The endeavor of constructing natural products—the organic molecules of nature—is justly called both a creative art and an exact science. Often called simply total synthesis, the replication of nature’s molecules in the laboratory reflects and symbolizes the state of the art of synthesis in general. In the last few decades a surge in total synthesis endeavors around the world led to a remarkable collection of achievements that covers a wide ranging landscape of molecular complexity and diversity. In this article, we present highlights of some of our contributions in the field of total synthesis of natural products of biological and medicinal importance. For perspective, we also provide a listing of selected examples of additional natural products synthesized in other laboratories around the world over the last few years.

show abstract

Total Synthesis and Confirmation of the Revised Structures of Azaspiracid‐2 and Azaspiracid‐3

Cited by 70 publications

References 53 publications

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Survey of marine natural product structure revisions: A synergy of spectroscopy and chemical synthesis

Microsphere-based immunoassay for the detection of azaspiracids

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

Contact Info

Product

Resources

About