A Matteson Homologation‐Based Synthesis of Doliculide and Derivatives

Tost, Markus; Andler, Oliver; Kazmaier, Uli

doi:10.1002/ejoc.202101345

Cited by 22 publications

(13 citation statements)

References 82 publications

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“…The OH-functionality of the commercially available nitrotyrosine ( 1 ) had to be protected to avoid side reactions during subsequent peptide coupling steps. In a previous synthesis we used an allyl protecting group [ 43 , 44 ], which can easily be removed with ruthenium catalysts [ 45 ], but because we were not sure if this protecting group would create problems during Alloc deprotection we decided to use a methoxymethyl (MEM) protecting group in this case ( Scheme 1 ). After N -Alloc protection of 1 [ 46 ] the carboxylic acid 2 was converted into methyl ester 3 to allow regioselective MEM-protection of the phenolic OH-functionality [ 47 ].…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives

2022

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Ilamycins/rufomycins are marine cycloheptapeptides containing unusual amino acids. Produced by Streptomyces sp., these compounds show potent activity against a range of mycobacteria, including multidrug-resistant strains of Mycobacterium tuberculosis. The cyclic peptides target the AAA+ protein ClpC1 that, together with the peptidases ClpP1/ClpP2, forms an essential ATP-driven protease. Derivatives of the ilamycins with a simplified tryptophane unit are synthesized in a straightforward manner. The ilamycin derivative 26 with a cyclic hemiaminal structure is active in the nM-range against several mycobacterial strains and shows no significant cytotoxicity. In contrast, derivative 27, with a glutamic acid at this position, is significantly less active, with MICs in the mid µM-range. Detailed investigations of the mode of action of 26 indicate that 26 deregulates ClpC1 activity and strongly enhances ClpC1-WT ATPase activity. The consequences of 26 on ClpC1 proteolytic activities were substrate-specific, suggesting dual effects of 26 on ClpC1-WT function. The positive effect relates to ClpC1-WT ATPase activation, and the negative to competition with substrates for binding to the ClpC1 NTD.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives

2022

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“…609 A new route to doliculide ( Dolabella auricularia ), making use of Matteson homologation methodology, has afforded the MNP and a small set of related analogues, some of which exhibit weak cytotoxicity towards the HCT-116 cell line. 610 Reviews describing SAR studies of aplyronine A, 611 dolastatin 10, 612 and cyclodepsipeptides of the aurilide family 613 were published in 2021. Investigation of the chemical diversity of the Australian nudibranch Ardeadoris rubroannulata afforded, amongst others, the 9 Z 1429 and 9 E 1430 isomers, facilitating correction of the previously proposed structure of pu'ulenal to that of the 9 Z isomer and assignment of the 9 E isomer as the new MNP isopu'ulenal.…”

Section: Molluscsmentioning

confidence: 99%

Marine natural products

et al. 2023

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“…Derived from the myxobacterium Paraliomyxa miuraensis [ 150 ], miuraenamides are cyclic depsipeptides containing a polyketide unit and an N-terminal alanine bound to an N-methylated halogenated aromatic amino acid, specifically tyrosine [ 144 ]. They inhibit cell migration, favor actin polymerization by stabilizing the oligomers formed during nucleation, and promote the assembly and stabilization of such filaments [ 151 ].…”

Section: Depsipeptides With a Recognized Mechanism Of Targeting Cance...mentioning

confidence: 99%

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

2023

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Cancer is currently considered one of the most threatening diseases worldwide. Diet could be one of the factors that can be enhanced to comprehensively address a cancer patient’s condition. Unfortunately, most molecules capable of targeting cancer cells are found in uncommon food sources. Among them, depsipeptides have emerged as one of the most reliable choices for cancer treatment. These cyclic amino acid oligomers, with one or more subunits replaced by a hydroxylated carboxylic acid resulting in one lactone bond in a core ring, have broadly proven their cancer-targeting efficacy, some even reaching clinical trials and being commercialized as “anticancer” drugs. This review aimed to describe these depsipeptides, their reported amino acid sequences, determined structure, and the specific mechanism by which they target tumor cells including apoptosis, oncosis, and elastase inhibition, among others. Furthermore, we have delved into state-of-the-art in vivo and clinical trials, current methods for purification and synthesis, and the recognized disadvantages of these molecules. The information collated in this review can help researchers decide whether these molecules should be incorporated into functional foods in the near future.

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A Matteson Homologation‐Based Synthesis of Doliculide and Derivatives

Cited by 22 publications

References 82 publications

Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives

Total Synthesis and Biological Evaluation of Modified Ilamycin Derivatives

Marine natural products

Depsipeptides Targeting Tumor Cells: Milestones from In Vitro to Clinical Trials

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