Seven new didemnins from the marine tunicate Trididemnum solidum

Sakai, Ryuichi; Stroh, Justin G.; Sullins, David W.; Rinehart, Kenneth L.

doi:10.1021/ja00118a010

Cited by 57 publications

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“…The metabolites were not identi®ed. Sakai et al 8 subsequently reported an open-chain didemnin, acyclodidemnin A, in which the ester linkage between Me 2 Tyr 5 and Thr 6 had been hydrolyzed (see Fig. 2).…”

Section: C L I N I C a L T R I A L Smentioning

confidence: 99%

“…Additional didemnin congeners were disclosed in a 1995 publication by Sakai et al 8 In addition to didemnin M, previously reported by Boulanger et al as didemnin H, Sakai et al 8 reported the structure for nordidemnin N, or [Norsta, 1 Tyr 5 ]didemnin B, another macrocycle-modi®ed congener. Other novel didemnins reported included a diastereomer of didemnin A, [epi-Hip 2 ]didemnin A.…”

mentioning

confidence: 97%

“…The authors cautioned that this tentative assignment was based on mass spectrometry analysis. 8 This result suggests that the ester linkage between N,O-Me 2 Tyr 5 and Thr 6 is especially susceptible to degradation. A rapid but unspeci®ed degradation of didemnin B during clinical trials was reported by Benvenuto et al, 21 a ®nding which could have signi®cant implications for clinical applications of didemnins.…”

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confidence: 98%

“…A numbering convention for didemnin nomenclature was reported, 8 and is illustrated in Figure 2. The macrocycle is numbered with isostatine as residue 1, Hip as residue 2, and so on.…”

mentioning

confidence: 99%

“…Using the systematic didemnin nomenclature, this compound would be called [Pyruvyl 9 ]didemnin B. Dehydrodidemnin B (aplidine), would later emerge as a second-generation clinical candidate. 17,18 In 1994, Boulanger et al 19 reported the structure and complete spectral assignment of a congener named didemnin H. This compound, in which the side chain peptide of didemnin B is acylated by a glutamine-pyroglutamic acid dipeptide, is also referred to by Rinehart et al as didemnin M. 8 The systematic description would be [Gln 10 , pGlu 11 ]didemnin B. In 1995, AbouMansour et al 20 reported the structures and anti-leukemia cytotoxicities of two novel didemnins: [Tyr 5 ]didemnin B and [D-Pro 4 ]didemnin B.…”

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confidence: 99%

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

Vera

Joullié

2002

Medicinal Research Reviews

141

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: C L I N I C a L T R I A L Smentioning

confidence: 99%

mentioning

confidence: 97%

mentioning

confidence: 98%

“…A numbering convention for didemnin nomenclature was reported, 8 and is illustrated in Figure 2. The macrocycle is numbered with isostatine as residue 1, Hip as residue 2, and so on.…”

mentioning

confidence: 99%

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

141

109

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Ascidians (Tunicates)–2

Kornprobst

2014

Encyclopedia of Marine Natural Products

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The article contains sections titled: Metabolites of Polyclinidae Long‐Chain Sulfated Alkanes and Terpenes of Sidnyum turbinatum Terpenes and Meroterpenes Para‐ and Metacyclophanes: Longithorones and Related Derivatives Simple Aromatic Derivatives Nitrogenous and Non‐Nitrogenous Macrolides Long‐Chain Amines and Amino Alcohols, Sphingosines Piperidine Alkaloids: Pseudodistomins Indole and β‐Carboline Alkaloids Quinoline and Pyridoacridine Alkaloids Bis‐Steroidal Alkaloids of Ritterella tokioka : Ritterazines Purines and Nucleosides Miscellaneous Nitrogenous Derivatives Metabolites of Ascidiidae Vanadium, Intracellular Acidity of Blood Cells, and Peptide Ligands Metabolites of Cionidae Metabolites of Diazonidae Metabolites of Perophoridae Metabolites Isolated from Species of the Genus Perophora Tetrahydroisoquinoline Alkaloids: Ecteinascidins Metabolites of Molgulidae and Pyuridae Lipids and Non‐Nitrogenous Derivatives Nitrogenous Derivatives, Antimicrobial Peptides, and Proteins Metabolites of Styelidae Non‐Nitrogenous Derivatives Phenylethylamine Derivatives, Various Alkaloids Antibacterial Purines and Peptides

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Marine Peptide Secondary Metabolites

Banaigs

Bonnard

Witczak

et al. 2014

Outstanding Marine Molecules

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A large pro port ion of the marine natural produc ts actu ally u n der clinical inve stigat ion are pept ide sec ondary metabolites with unusual amino acids re sidues. This growing f amily of compounds can be produced via tw o major p athw ays, r ibosomal and nonribosomal. In this c hapt er a re p re sent ed a nd illu strated, with a fe w f amou s examples, ribosomal-and n onribosomal-d erived pe ptides. Atte ntion is focused on fi ve families of biological ly a ctive marine p eptides of d iverse origin, ranging from the old est living ce ll of the world, the cyanobact eria, to more sophisticat ed organisms s uch a s tu nicates or mol lusk s. T he discu ssed pe ptides illu strate d iff erently th e s tructural fe atu re s and diversity f ound in mari ne-derived peptid es; laxaphycins as an example o f true pept ide s; dolast atins, didemnins and kahalalides are discuss ed in connectio n wit h their cl inical trials; a nd azole/azoli ne-c ontaining cyanobactins to exe m plif y the extra ord ina ry c hemi cal dive rs it y wit hin a single organism. Information abou t their biol ogical properties and mec hanisms of a ctio n is disc uss ed when available .

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Seven new didemnins from the marine tunicate Trididemnum solidum

Cited by 57 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

Ascidians (Tunicates)–2

Marine Peptide Secondary Metabolites

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