Total Synthesis and Structural Revision of Aeruginosin KT608A

Scherer, Manuel; Gademann, Karl

doi:10.1021/acs.orglett.7b01822

Cited by 16 publications

(18 citation statements)

References 29 publications

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“…The transformation from alcohol 12 to 13 was achieved by the Dess–Martin oxidation, followed by selective reduction as well as TES protection. Corroborating our earlier configurational hypothesis, 1 H NMR analysis of 13 revealed the coupling constant between H4′ and H5′ to be J = 9.6 Hz, suggesting that the carbohydrate segment of mangrolide D is not vancosamine but 4′- epi -vancosamine instead …”

supporting

confidence: 82%

Total Synthesis and Structural Revision of Mangrolide D

2019

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The unique 18-membered macrocyclic natural product mangrolide D was prepared in totally synthetic form. Key steps feature an Au-catalyzed glycosylation, aza-Michael addition, and LaLi3tris(binaphthoxide) catalyzed epoxidation. Detailed analysis of the constitution and configuration of the carbohydrate segment and the total synthesis of the revised structure led to structural revision of the originally proposed structure.

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confidence: 82%

Total Synthesis and Structural Revision of Mangrolide D

2019

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“…The cytotoxicity of purified 1 was around five times greater than the extract, but remains roughly one order of magnitude weaker than other cyanobacterial toxins. [27][28][29][30][31][32][33][34][35][36][37] To understand the mechanism of action of microviridin 1777 (1), an enzyme assay with trypsin, chymotrypsin, and elastase was performed (Figure 4) using modified literature procedures. 31,45 Whereas only weak inhibition of trypsin could be observed (IC50 > 10 µM), microviridin 1777 (1)…”

Section: Resultsmentioning

confidence: 99%

“…24 These research tools have been particularly successful in the analysis of cyanobacterial extracts [25][26][27][28] recently highlighted by the global metabolomics study of Microcystis. 29 In the context of our work on new cyanobacterial toxins, [30][31][32][33][34][35][36] we have postulated that strong protease inhibitors can display biological effects beyond deterrence leading to fatal effects on grazers. Experimental support for this hypothesis is documented in a number of studies, [37][38][39][40] providing evidence that peptides from different classes such as cyanopeptolins and aeruginosins can display strong grazer toxicity.…”

mentioning

confidence: 99%

“…Experimental support for this hypothesis is documented in a number of studies, [37][38][39][40] providing evidence that peptides from different classes such as cyanopeptolins and aeruginosins can display strong grazer toxicity. [31][32][33][34]41 In order to further corroborate the production of multiple toxins by cyanobacteria, we were interested in potent protease inhibitors from other classes, which…”

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confidence: 99%

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Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach

et al. 2020

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The toxicity of the cyanobacterium Microcystis aeruginosa EAWAG 127a was evaluated against the sensitive grazer Thamnocephalus platyurus, and the extract possessed strong activity. To investigate the compounds responsible for cytotoxicity, a series of peptides from this cyanobacterium were studied using a combined genomic and molecular networking approach. The results led to the isolation, structure elucidation, and biological evaluation of microviridin 1777, which represents the most potent chymotrypsin inhibitor characterized from this family of peptides to date. Furthermore, the biosynthetic gene clusters of microviridin, anabaenopeptin, aeruginosin, and piricyclamide were located in the producing organism, and six additional natural products were identified by tandem mass spectrometry analyses. These results highlight the potential of modern techniques for the identification of natural products, demonstrate the ecological role of protease inhibitors produced by cyanobacteria, and raise ramifications concerning the presence of novel, yet uncharacterized, toxin families in cyanobacteria beyond microcystin.

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“…Hydroindole or hydrobenzofuran structures bearing a carbonyl group at the 2-position are often contained in natural and bioactive compounds. 108) Most hydroindole synthetic protocol rely on the utilization of indoline-2-carboxylic acid or tyrosine as a synthetic building block, 109) limiting divergent syntheses. Furthermore, the preparation of an α-oxidized carbonyl functionality requires an umpolung process or the α-amination/alkoxylation of carbonyl compounds with highly toxic nitrogen electrophiles or explosive peroxides.…”

Section: Synthesis Of Tetrahydrobenzofuranones Bearing a Chiral Tetramentioning

confidence: 99%

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

Takizawa

2020

Chem. Pharm. Bull.

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Organocatalytic enantioselective domino reactions are an extremely attractive methodology, as their use enables the construction of complex chiral skeletons from readily available starting materials in two or more steps by a single operation under mild reaction conditions. Thus, these reactions can save both the quantity of chemicals and length of time typically required for the isolation and/or purification of synthetic intermediates. Additionally, no metal contamination of the products occurs, given that organocatalysts include no expensive or toxic metals. The aza-Morita-Baylis-Hillman (aza-MBH) reaction is an atom-economical carbon-carbon bond-forming reaction between α,β-unsaturated carbonyl compounds and imines mediated by Lewis base (LB) catalysts, such as nucleophilic phosphines and amines. aza-MBH products are functionalized chiral β-amino acid derivatives that are highly valuable as pharmaceutical raw materials. Although various enantioselective aza-MBH processes have been investigated, very few studies of aza-MBH-type domino reactions have been reported due to the complexity of the aza-MBH process, which involves a Michael/ Mannich/H-transfer/β-elimination sequence. Accordingly, in this review article, our recent efforts in the development of enantioselective domino reactions initiated by MBH processes are described. In the domino reactions, chiral organocatalysts bearing Brønsted acid (BA) and/or LB units impart synergistic activation to substrates, leading to the easy synthesis of highly functionalized heterocycles (some of which have tetrasubstituted and/or quaternary carbon stereocenters) in high yield and enantioselectivity.

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Total Synthesis and Structural Revision of Aeruginosin KT608A

Cited by 16 publications

References 29 publications

Total Synthesis and Structural Revision of Mangrolide D

Total Synthesis and Structural Revision of Mangrolide D

Microviridin 1777: A Toxic Chymotrypsin Inhibitor Discovered by a Metabologenomic Approach

Organocatalytic Synthesis of Highly Functionalized Heterocycles by Enantioselective aza-Morita–Baylis–Hillman-Type Domino Reactions

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