Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology

Sato, Hiroshi; Yoshida, Masahito; Murase, Hayato; Nakagawa, Hiroshi; Doi, Takayuki

doi:10.1021/acscombsci.6b00076

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…After conversion to the mono-TBS ether 11 in two steps, stepwise oxidation of the primary alcohol in 11 afforded the α-hydroxy acid derivative 7 . The resulting acid 7 was subsequently coupled with the 3-methyl- l -proline derivative 6 using PyBroP/DIEA to provide the amide 12 in 46% yield. Finally, removal of the benzyl group in 12 by hydrogenolysis afforded the desired acylproline derivative 5 .…”

Section: Resultsmentioning

confidence: 99%

Structure Revision of Trichomide D by Total Synthesis

et al. 2022

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A structure revision of trichomide D has been achieved by its total synthesis. The sterically hindered peptide sequence was successfully prepared using not only a conventional amidation with EDCI but also coupling with an Fmoc-protected amino acid chloride derivative. The cyclization precursor was synthesized by coupling of a tetrapeptide with an acylproline derivative and subsequent removal of silyl groups at the N-and Ctermini. Macrolactonization using MNBA/DMAPO followed by preparation of a chlorohydrin moiety furnished the proposed structure of trichomide D, whose spectra were not identical to those of the natural product. Finally, we succeeded in the elucidation of the true structure of trichomide D by its total synthesis, and the absolute configuration of the chlorohydrin moiety was revised to be S. The cytotoxicities of the natural product and its synthetic derivatives against MCF-7 and HeLa S3 cells were evaluated by the MTT method, revealing that the configuration of the chlorohydrin moiety is a pivotal factor for exhibiting potent cytotoxicity against cancer cells.

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Section: Resultsmentioning

confidence: 99%

Structure Revision of Trichomide D by Total Synthesis

et al. 2022

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“…NTU492 was cultured in solid state, and seven compounds including four new peptides 1 – 4 and three known compounds were obtained from the fermented products. The known compounds, destruxin B, guangomide A, and guangomide B were identified by comparison of spectroscopic data with literatures [ 11 – 13 ].…”

Section: Resultsmentioning

confidence: 99%

Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells

Hsiao¹,

Wang²,

Chiang³

et al. 2020

Journal of Food and Drug Analysis

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“…Using the Split-and-Pool Method 45,46) Based on synthetic methods for destruxin E (1), as mentioned above, a combinatorial synthesis of destruxin E analogs was attempted using the split-and-pool method. 47) We designed the analogs referring to the structure of destruxins and related derivatives previously isolated from natural sources, and planned to synthesize eighteen analogs containing amino acids A, B, and C, as shown in Chart 6.…”

Section: Combinatorial Synthesis Of Destruxin Analogsmentioning

confidence: 99%

Combinatorial Synthesis and Biological Evaluation of Destruxins

Yoshida

2019

Chem. Pharm. Bull.

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The combinatorial synthesis and biological evaluation of destruxins are described herein. First, the total synthesis of destruxin E was achieved, and its absolute configuration was successfully determined to be (S). In addition, the preparation of a combinatorial library based on the structure of destruxins was carried out by the split-and-pool method. Biological evaluation of the resulting analogs against osteoclast-like multinuclear cells (OCLs) revealed that the N-methyl-alanine residue was crucial to inducing morphological changes in OCLs. In particular, functionalization at the β-position of the proline (Pro) residue was found to be tolerant of the desired biological activity of destruxin E, suggesting that the β-position of the Pro residue should be a promising site for the introduction of a chemical tag toward the preparation of a molecular probe. Key words natural product; cyclic peptide; total synthesis; combinatorial library 3. Total Synthesis and Structure Determination of Destruxin E (1) 33) Toward understanding the structure-activity relationship Chart 1. Preparation of Cyclization Precursors

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Combinatorial Solid-Phase Synthesis and Biological Evaluation of Cyclodepsipeptide Destruxin B as a Negative Regulator for Osteoclast Morphology

Cited by 8 publications

References 54 publications

Structure Revision of Trichomide D by Total Synthesis

Structure Revision of Trichomide D by Total Synthesis

Anti-inflammatory effects of peptides from a marine algicolous fungus Acremonium sp. NTU492 in BV-2 microglial cells

Combinatorial Synthesis and Biological Evaluation of Destruxins

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