Total synthesis and structural investigations of didemnins A, B, and C

Li, Wen Ren; Ewing, William R.; Harris, Bruce D.; Joullié, Madeleine M.

doi:10.1021/ja00177a030

Cited by 147 publications

(101 citation statements)

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“…145 These targets were obtained using the general approaches taken for the synthesis of the natural products. 77,79 Both compounds, which contain the dimethylaminocoumarin uorophore in the side chain, have shown cytotoxic activity similar to that of didemnin B in the NCI-60 tumor cell screen. 99 Recent studies have demonstrated that several species of fresh-and salt-water ®sh develop a learned avoidance response upon ingestion of the didemnin and tamandarin derivatives.…”

Section: Fluorescent Didemnin and Tamandarin Ligandsmentioning

confidence: 97%

“…76 The Joullie Â synthesis differs conceptually from the other synthetic efforts in that it incorporates strategic elements of stereocontrol at both the Ist 1 and Hip 2 moieties from the outset. 77 The additional post-cyclization manipulation of advanced intermediates complicates and lengthens this approach, but it does not rely on the inversion of the methyl group con®guration at Hip 2 . After undergoing several re®nements to improve the yields of key transformations, this strategy has been used to synthesize several analogs of didemnins containing structural changes throughout the molecule.…”

Section: T O T a L S Y N T H E S I S O F N A T U R A L D I D E M N mentioning

confidence: 99%

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Natural products as probes of cell biology: 20 years of didemnin research

Vera

Joullié

2002

Medicinal Research Reviews

143

109

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The discovery of the didemnin family of marine depsipeptides launched an exciting and intriguing chapter in natural product chemistry. The unusual structure of the didemnin congeners has led to several total syntheses by research groups from around the world. The impressive in vitro and in vivo biological activities of the didemnins resulted in the first human clinical trials in the U.S. of a marine natural product against cancer, and additional clinical trials of a second-generation didemnin, dehydrodidemnin B (aplidine), are underway. As we mark the 20-year anniversary of the discovery of the didemnins, this class of natural products continues to stimulate active research in fields ranging from synthetic and medicinal chemistry to clinical oncology and cell biology. While some progress was made in dissecting the molecular mechanism of action and in establishing structure-activity relationships, there are still more questions than answers. This review covers the recent didemnin literature, highlighting the work directed towards understanding how this group of natural products interact with fundamental processes such as cell proliferation, protein biosynthesis, and apoptosis. The didemnin field illustrates how natural product chemistry may be used as a critical tool for the study of cell biology.

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Section: Fluorescent Didemnin and Tamandarin Ligandsmentioning

confidence: 97%

Section: T O T a L S Y N T H E S I S O F N A T U R A L D I D E M N mentioning

confidence: 99%

Natural products as probes of cell biology: 20 years of didemnin research

Vera

Joullié

2002

Medicinal Research Reviews

143

109

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“…The substrates used are shown in Table 3. The phenyl derivative 5a was obtained from methyl mandelate, 5b from valine [24] via standard protocols. The polyoxygenated derivatives 5c and 5d were synthesized starting from mannitol, 5e from tartaric acid.…”

mentioning

confidence: 99%

Substrate‐Controlled Palladium‐Catalyzed Allylic Alkylations of Chelated Enolates – Scope and Limitations

Lindner

Kazmaier

2005

Adv Synth Catal

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Chelated enolates of amino acid derivatives were found to be excellent nucleophiles for stereoselective palladium-catalyzed allylic alkylations via terminal p-allyl complexes. Neither the olefin geometry (linear substrates) nor the configuration of secondary allylic substrates has an influence on the newly formed stereogenic centre of the amino acid. This is exclusively controlled by the protecting group on the chiral centre. Therefore, depending on the protecting group used, both diastereomeric amino acids can be obtained in a highly stereoselective fashion (up to 96% ds for 1,5 induction) from one allylic alcohol.

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“…The stereochemistry of chloro N , O -di Me Tyr was determined by synthesis of the same using N , O -di Me- l -Tyr and sulfuryl chloride [10]. Comparison of spectral data of 1 with the literature [11,12] revealed the stereochemistry of isoSta and Hip moieties to be similar to that in didemninA. Thus, the structure of compound 1 was established as N , O -diMe- o -chlorotyrosine derivative of didemnin A.…”

Section: Resultsmentioning

confidence: 99%

Chlorinated Didemnins from the Tunicate Trididemnum solidum

et al. 2013

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Chemical investigation of the tunicate Trididemnum solidum resulted in the isolation of two new chlorinated compounds belonging to the didemnin class, along with two known compounds didemnin A and didemnin B. The structural determination of the compounds was based on extensive NMR and mass spectroscopic analysis. The isolated compounds 1–4 were tested for their anti-inflammatory activity using in vitro assays for inhibition of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB) activity. The anti-cell proliferative activity of the above compounds was also evaluated against four solid tumor cell lines.

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Total synthesis and structural investigations of didemnins A, B, and C

Cited by 147 publications

References 0 publications

Natural products as probes of cell biology: 20 years of didemnin research

Natural products as probes of cell biology: 20 years of didemnin research

Substrate‐Controlled Palladium‐Catalyzed Allylic Alkylations of Chelated Enolates – Scope and Limitations

Chlorinated Didemnins from the Tunicate Trididemnum solidum

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