Tandem Diels−Alder/Fragmentation Approach to the Synthesis of Eleutherobin

Winkler, Jeffrey D.; Quinn, Kevin J.; MacKinnon, Colin H.; Hiscock, and Steven D.; McLaughlin, Emily C.

doi:10.1021/ol0345226

Cited by 65 publications

(27 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Western Australia is also the origin of the soft coral Elutherobia sp, from which the diterpene glycoside eleutherobin was first isolated and identified as a potent tubulin polymerization agent with significant anti-cancer potential [36], [37]. Due to difficulties in obtaining permits for recollection, this compound was subject to an intensive synthetic research effort based in the USA [38], [39], [40]. Simpler analogues were synthesised [41], [42] and explored for therapeutic potential [43].…”

Section: Introductionmentioning

confidence: 99%

Phylogeny Drives Large Scale Patterns in Australian Marine Bioactivity and Provides a New Chemical Ecology Rationale for Future Biodiscovery

et al. 2013

View full text Add to dashboard Cite

Twenty-five years of Australian marine bioresources collecting and research by the Australian Institute of Marine Science (AIMS) has explored the breadth of latitudinally and longitudinally diverse marine habitats that comprise Australia’s ocean territory. The resulting AIMS Bioresources Library and associated relational database integrate biodiversity with bioactivity data, and these resources were mined to retrospectively assess biogeographic, taxonomic and phylogenetic patterns in cytotoxic, antimicrobial, and central nervous system (CNS)-protective bioactivity. While the bioassays used were originally chosen to be indicative of pharmaceutically relevant bioactivity, the results have qualified ecological relevance regarding secondary metabolism. In general, metazoan phyla along the deuterostome phylogenetic pathway (eg to Chordata) and their ancestors (eg Porifera and Cnidaria) had higher percentages of bioactive samples in the assays examined. While taxonomy at the phylum level and higher-order phylogeny groupings helped account for observed trends, taxonomy to genus did not resolve the trends any further. In addition, the results did not identify any biogeographic bioactivity hotspots that correlated with biodiversity hotspots. We conclude with a hypothesis that high-level phylogeny, and therefore the metabolic machinery available to an organism, is a major determinant of bioactivity, while habitat diversity and ecological circumstance are possible drivers in the activation of this machinery and bioactive secondary metabolism. This study supports the strategy of targeting phyla from the deuterostome lineage (including ancestral phyla) from biodiverse marine habitats and ecological niches, in future biodiscovery, at least that which is focused on vertebrate (including human) health.

show abstract

Section: Introductionmentioning

confidence: 99%

Phylogeny Drives Large Scale Patterns in Australian Marine Bioactivity and Provides a New Chemical Ecology Rationale for Future Biodiscovery

et al. 2013

View full text Add to dashboard Cite

show abstract

“…The ether derivatives M1 and M2 were obtained by the reaction of schizonepetin with alkyl iodides in the presence of silver oxide in CH 3 CN according to the reported procedure as shown in Scheme 1 [21]. …”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

Bao

Zheng

et al. 2013

IJMS

View full text Add to dashboard Cite

A series of schizonepetin derivatives have been designed and synthesized in order to obtain potent antivirus agents. The antiviral activity against HSV-1 and influenza virus H3N2 as well as the cytotoxicity of these derivatives was evaluated by using cytopathic effect (CPE) inhibition assay in vitro. Compounds M2, M4, M5 and M34 showed higher inhibitory activity against HSV-1 virus with the TC50 values being in micromole. Compounds M28, M33, and M35 showed higher inhibitory activity against influenza virus H3N2 with their TC50 values being 96.4, 71.0 and 75.4 μM, respectively. Preliminary biological activity evaluation indicated that the anti-H3N2 and anti-HSV-1 activities improved obviously through the introduction of halogen into the structure of schizonepetin.

show abstract

“…58 The most advanced product obtained so far seems already to contain all of the important features of the backbone, so that only a few steps (on paper) need to be achieved for reaching the target molecule.…”

Section: Funk's Approach 40mentioning

confidence: 99%

“…Recently, more convergent approaches and thus more practical synthetic strategies have been suggested by Royer, 57 Mann, 55 Magnus 56 and Winkler. 58 Royer started with furanone 188 (Scheme 27). 57 Acylation of the corresponding anion with acyl chloride 192 led to formation of all four possible stereoisomers in equal amounts.…”

Section: Synthetic Approaches To Eleutherobin By Other Groupsmentioning

confidence: 99%

Recent advances in the total synthesis of pharmaceutically relevant diterpenes

Busch

Kirschning

2008

Nat. Prod. Rep.

View full text Add to dashboard Cite

A detailed overview is presented of recent total synthesis approaches to four different diterpenoids--the ginkgolides, tonantzitlolone, ingenol and eleutherobin. Due to their structural complexity, all pose major challenges for total synthesis, guaranteeing diverse strategic tours de force and a rich synthetic chemistry. Additionally, all four diterpenoids are of major relevance because of their biological (target) or pharmaceutical properties.

show abstract

Tandem Diels−Alder/Fragmentation Approach to the Synthesis of Eleutherobin

Cited by 65 publications

References 41 publications

Phylogeny Drives Large Scale Patterns in Australian Marine Bioactivity and Provides a New Chemical Ecology Rationale for Future Biodiscovery

Phylogeny Drives Large Scale Patterns in Australian Marine Bioactivity and Provides a New Chemical Ecology Rationale for Future Biodiscovery

Design, Synthesis and Antiviral Activity Studies of Schizonepetin Derivatives

Recent advances in the total synthesis of pharmaceutically relevant diterpenes

Contact Info

Product

Resources

About