The Miharamycins and Amipurimycin: their Structural Revision and the Total Synthesis of the Latter

Wang, Shengyang; Zhang, Qingju; Zhao, Yu; Sun, Jiansong; Kang, Wenjia; Wang, Fei; Pan, Hai‐Xue; Tang, Gong‐Li; Yu, Biao

doi:10.1002/ange.201905723

Cited by 8 publications

(1 citation statement)

References 46 publications

(22 reference statements)

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“…The guanidine system is present in structural components of biomolecules, namely in the amino acid arginine or in the nucleobase guanine. It is also embodied in the nitrogenous aromatic moiety of various bioactive compounds, such as in the 2aminopurine motif, which is contained in the antibiotic natural nucleosides amipurimycin and miharamycins [22,23], and in various synthetic nucleosides exhibiting anticancer [24] and antiviral properties [25], or in the 2-aminopyrimidine moiety, which is present in the anticancer drug imatinib [26]. On the other hand, the amidine (or imidamide) system (NH2-C=NR) contained in the guanidine group is present in the cytosine and adeninebased motifs, which are found in various nucleoside analogues used as chemotherapeutic agents [27,28].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives

Xavier

Fortuna

Gonçalves-Pereira

et al. 2021

Preprint

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The synthesis of novel guanidino sugars as potential mimetics of nucleosides and their biological evaluation is described. 5-Guanidino xylofuranoses containing different O-substituents at C-3, including saturated/unsaturated hydrocarbon chains and aromatic-containing moieties, were accessed from 5-azido xylofuranose precursors through reduction followed by guanidinylation of the obtained amines with N,N′-bis(tert-butoxycarbonyl)-N′′-triflylguanidine. A 5-azido 3-O-methyl-branched N-benzyltriazole isonucleoside was converted into the corresponding 5-guanidino-containing isonucleoside, whose structure includes both the guanidine and triazole moieties as nucleobase-like motifs connected to the xylofuranose template. In alternative, this structurally new type of compound was synthesized via cycloaddition between a 5-guanidino-3-O-propargyl xylofuranose derivative and benzyl azide in the presence of a CuI/Amberlyst A-21 catalytic system, along with the 5-iodotriazole derivative as a secondary product, which, in turn was the sole product when using equimolar CuI and a catalytic amount of 4-dimethylaminopyridine. A guanidinomethyltriazole 3′-O-dodecyl xylofuranos-5′-yl isonucleoside, which comprise a novel isonucleosidic framework having a guanidine system appended on the sugar-linked triazole motif, was obtained from the related aminomethyltriazole 5’-isonucleoside via guanidinylation. Bioactivity screening revealed 2 compounds as selective inhibitors of acetylcholinesterase (AChE), namely the guanidinomethyltriazole derivative, with moderate inhibition (Ki = 22.87 µM) and the 3-O-dodecyl (N-Boc)guanidino xylofuranose, which was the most active compound (Ki = 7.49 µM) acting as a non-competitive inhibitor. The latter also displayed moderate antiproliferative effects in chronic myeloid leukemia (K562, GI50 =31.02 μM) and in breast cancer (MCF-7, GI50 = 26.89 μM) cells. The aminomethyltriazole 5’-isonucleoside was the most potent molecule with single-digit micromolar GI50 values against both cells (GI50 = 6.33 μM and 8.45 μM), similar to that of the standard drug 5-fluorouracil against MCF-7 cells.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives

Xavier

Fortuna

Gonçalves-Pereira

et al. 2021

Preprint

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Total Synthesis and Stereochemistry Assignment of Nucleoside Antibiotic A‐94964

Shao

Zheng

et al. 2022

Angewandte Chemie

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Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycin B and Its Biosynthetic Precursor

et al. 2022

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Miharamycins belong to a class of peptidyl nucleoside antibiotics with a unique nine-carbon pyranosyl amino acid core and a rare 2-aminopurine moiety. Herein, we report the de novo total synthesis of miharamycin B and its biosynthetic precursor from 3bromofuran and Garner's aldehyde through a modified Achmatowicz reaction. Many challenges were resolved toward the de novo synthesis of miharamycin B, including the introduction of a dense array of functional groups, the stereoselective construction of consecutive stereocenters, dealing with the variability of the anomeric positions, and promoting site-selectivity in the cyclization to form the tetrahydrofuran ring. This de novo synthesis strategy enables efficient preparation of 3'-substituted saccharides, allowing the study of their structure-activity relationships and mode of action, and meets the growing demand for the development of novel antibiotics inspired by miharamycin natural products.

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The Miharamycins and Amipurimycin: their Structural Revision and the Total Synthesis of the Latter

Cited by 8 publications

References 46 publications

Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives

Synthesis and Exploitation of the Biological Profile of Novel Guanidino Xylofuranose Derivatives

Total Synthesis and Stereochemistry Assignment of Nucleoside Antibiotic A‐94964

Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycin B and Its Biosynthetic Precursor

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