Antineoplastic Agents. 599. Total Synthesis of Dolastatin 16

Pettit, George R.; Smith, Thomas H.; Arce, Pablo M.; Flahive, Erik J.; Anderson, Collin; Chapuis, Jean‐Charles; Xu, Jun‐Ping; Groy, Thomas L.; Belcher, Paul E.; Macdonald, Christian B.

doi:10.1021/np500925y

Cited by 20 publications

(19 citation statements)

References 18 publications

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“…Lastly, the Shiina protocol 30 was used for macrolactonization to afford 1 in 31% overall yield (two steps), because other procedures such as the Yamaguchi lactonization 31 did not provide the desired product. All data ( 1 H and 13 C NMR, HRMS, and optical properties) for synthetic 1 were identical to those reported by Pettit and co-workers 13,17 for the natural and synthetic samples.…”

Section: Please Do Not Adjust Marginssupporting

confidence: 83%

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Total synthesis and biological activity of dolastatin 16

et al. 2017

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The total synthesis of dolastatin 16, a macrocyclic depsipeptide first isolated from the sea hare Dolabella auricularia as a potential antineoplastic metabolite by Pettit et al., was achieved in a convergent manner. Dolastatin 16 was reported by Tan to exhibit strong antifouling activity, and thus shows promise for inhibiting the attachment of marine benthic organisms such as Amphibalanus amphitrite to ships and submerged artificial structures. Therefore, dolastatin 16 is a potential compound for a new, environmentally friendly antifouling material to replace banned tributyltin-based antifouling paints. The synthesis of dolastatin 16 involved the use of prolinol to prevent formation of a diketopiperazine composed of L-proline and N-methyl-D-valine during peptide coupling. This strategy for the elongation of peptide chains allowed the efficient and scalable synthesis of one segment, which was subsequently coupled with a second segment and cyclized to form the macrocyclic framework of dolastatin 16. The synthetic dolastatin 16 exhibited potent antifouling activity similar to that of natural dolastatin 16 toward cypris larvae of Amphibalanus amphitrite.

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Section: Please Do Not Adjust Marginssupporting

confidence: 83%

“…In addition, the MCF-7 cell results agreed with those in the report by Pettit (GI 50 >10 g/mL). 17 The LC 50 value of 16 on MCF-7 cells (LC 50 > 100 µg/mL) was much greater than the value produced by 25 (LC 50 between 10 and 30 µg/mL) containing unusual amino acids.…”

Section: Please Do Not Adjust Marginsmentioning

confidence: 90%

Total synthesis and biological activity of dolastatin 16

et al. 2017

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“…Its mean GI 50 in the NCI 60 cell line panel was ∼0.3 μM and COMPARE analyses provided relatively low correlations with dolastatin 10 ( p = 0.76) and dolastatin 15 ( p = 0.71) . The total synthesis of dolastatin 16 consisting of 23 steps was recently achieved . Interestingly, Pettit et al .…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…The total synthesis of dolastatin 16 consisting of 23 steps was recently achieved . Interestingly, Pettit et al . report that the synthetic dolastatin 16, while otherwise identical (by X‐ray crystal structure and spectral characteristics) with the natural product, did not reproduce the nanomolar cancer cell growth inhibition displayed by the natural isolate.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

“…report that the synthetic dolastatin 16, while otherwise identical (by X‐ray crystal structure and spectral characteristics) with the natural product, did not reproduce the nanomolar cancer cell growth inhibition displayed by the natural isolate. Pettit et al . reported that presumably this result can be attributed to the conformation(s) of the synthetic dolastatin 16 or to a chemically undetected component isolated with the natural product.…”

Section: Mollusk‐derived Anticancer Agentsmentioning

confidence: 99%

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Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Ciavatta

Lefranc

Carbone

et al. 2016

Medicinal Research Reviews

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The chemical investigation of marine mollusks has led to the isolation of a wide variety of bioactive metabolites, which evolved in marine organisms as favorable adaptations to survive in different environments. Most of them are derived from food sources, but they can be also biosynthesized de novo by the mollusks themselves, or produced by symbionts. Consequently, the isolated compounds cannot be strictly considered as “chemotaxonomic markers” for the different molluscan species. However, the chemical investigation of this phylum has provided many compounds of interest as potential anticancer drugs that assume particular importance in the light of the growing literature on cancer biology and chemotherapy. The current review highlights the diversity of chemical structures, mechanisms of action, and, most importantly, the potential of mollusk‐derived metabolites as anticancer agents, including those biosynthesized by mollusks and those of dietary origin. After the discussion of dolastatins and kahalalides, compounds previously studied in clinical trials, the review covers potentially promising anticancer agents, which are grouped based on their structural type and include terpenes, steroids, peptides, polyketides and nitrogen‐containing compounds. The “promise” of a mollusk‐derived natural product as an anticancer agent is evaluated on the basis of its ability to target biological characteristics of cancer cells responsible for poor treatment outcomes. These characteristics include high antiproliferative potency against cancer cells in vitro, preferential inhibition of the proliferation of cancer cells over normal ones, mechanism of action via nonapoptotic signaling pathways, circumvention of multidrug resistance phenotype, and high activity in vivo, among others. The review also includes sections on the targeted delivery of mollusk‐derived anticancer agents and solutions to their procurement in quantity.

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Synthesis and Structure−Activity Relationship of Omaezallene Derivatives

Umezawa

Prakoso

Kannaka

et al. 2019

Chemistry & Biodiversity

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Omaezallene derivatives (nor‐bromoallene, nor‐bromodiene, and bromoenynes) were successfully synthesized. Their antifouling activity and toxicity to the cypris larvae of the barnacle Amphibalanus amphitrite and ecotoxicity to the marine crustacean Tigriopus japonicus were studied. It was revealed that the two side chains of omaezallene were essential to its antifouling activity because the activities of nor‐bromoallene and nor‐bromodiene were significantly diminished. The bromoenyne was found to exhibit potent antifouling activities comparable to omaezallene with low toxicity and ecotoxicity. Preparation of bromoenyne framework is much easier than that of bromodiene moiety in omaezallene. Based on the antifouling activities of the bromoenynes, the synthesis of fluorescent probes and evaluation of their biological activities were also carried out.

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Antineoplastic Agents. 599. Total Synthesis of Dolastatin 16

Cited by 20 publications

References 18 publications

Total synthesis and biological activity of dolastatin 16

Total synthesis and biological activity of dolastatin 16

Marine Mollusk‐Derived Agents with Antiproliferative Activity as Promising Anticancer Agents to Overcome Chemotherapy Resistance

Synthesis and Structure−Activity Relationship of Omaezallene Derivatives

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