Total Synthesis and Stereochemical Reassignment of Mandelalide A

Lei, Honghui; Jia, Yan; Yu, Jie; Liu, Yuqing; Wang, Zhuo; Xu, Zhengshuang; Ye, Tao

doi:10.1002/anie.201403542

Cited by 81 publications

(85 citation statements)

References 41 publications

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“…However, previously, we used molecular mechanics conformational searches, quantum mechanical NMR chemical shift predictions, and DP4 analyses to support revised absolute structures of 1–4 , 13 with 1 being used as a reference model after its earlier revision by total synthesis. 5 Thus, we propose the absolute configuration of the macrocycle in 6 as shown. The relative configuration of the new butyrylated keto-sugar in 6 , formally 5-(butyryloxy)-2-hydroxy-3-methoxy-6-methyl-4-oxotetrahydro-2H-pyran, can be proposed from homonuclear coupling constants and ROESY correlations.…”

Section: Resultsmentioning

confidence: 99%

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors

et al. 2017

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Mandelalides A–D (1–4) are macrocyclic polyketides known to have an unusual bioactivity profile influenced by compound glycosylation and growth phase of cultured cells. The isolation and characterization of additional natural congeners, mandelalides E–L (5–12), and the supply of synthetic compounds 1 and 12, as well as seco-mandelalide A methyl ester (13), have now facilitated mechanism of action and structure-activity relationship studies. Glycosylated mandelalides are effective inhibitors of aerobic respiration in living cells. Macrolides 1 and 2 inhibit mitochondrial function similar to oligomycin A and apoptolidin A, selective inhibitors of the mammalian ATP synthase (complex V). 1 inhibits ATP synthase activity from isolated mitochondria and triggers caspase-dependent apoptosis in HeLa cells, which are more sensitive to inhibition by 1 in the presence of the glycolysis inhibitor 2-deoxyglucose. Thus, mandelalide cytotoxicity depends on basal metabolic phenotype; cells with an oxidative phenotype are most likely to be inhibited by the mandelalides.

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Section: Resultsmentioning

confidence: 99%

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors

et al. 2017

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“…Then, after the total synthesis of three isomers, they found that the NMR data of 35 agreed satisfactorily well with the natural product . In the meantime, the Xu, Ye, and co‐workers, independently reached the same conclusion by finding that the upper side of the molecule was the source of the problem, with all the corresponding stereocenters inverted …”

Section: Dp4mentioning

confidence: 99%

Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations

Grimblat

Sarotti

2016

Chemistry A European J

193

147

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The calculations of NMR properties of molecules using quantum chemical methods have deeply impacted several branches of organic chemistry. They are particularly important in structural or stereochemical assignments of organic compounds, with implications in total synthesis, stereoselective reactions, and natural products chemistry. In studying the evolution of the strategies developed to support (or reject) a structural proposal, it becomes clear that the most effective and accurate ones involve sophisticated procedures to correlate experimental and computational data. Owing to their relatively high mathematical complexity, such calculations (CP3, DP4, ANN-PRA) are often carried out using additional computational resources provided by the authors (such as applets or Excel files). This Minireview will cover the state-of-the-art of these toolboxes in the assignment of organic molecules, including mathematical definitions, updates, and discussion of relevant examples.

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“…Removal of the acetyl groups in 135 with NaOMe afforded jadomycins B (128) in 89% yield (3aS : 3aR ¼ 3 : 2). Similar glycosylations of aglycones 136 and 137 provided glycosides 138 and 139 (62%, a : b ¼ 5 : 1 for 136; 60%, a : b ¼ 10 : 1 for 137).…”

Section: Syntheses With Heteroaryl Thioglycosidesmentioning

confidence: 99%

O-Glycosylation methods in the total synthesis of complex natural glycosides

2015

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The total syntheses of 33 complex natural O-glycosides, such as the glycosides of macrocyclic lactones/lactams, enediynes, angucyclines, and anthracyclines, are highlighted, with a major focus being placed on the O-glycosylation reactions which connect the saccharides and the aglycones. These successful O-glycosylation reactions employ such donors as glycosyl bromides, fluorides, iodides, trichloroacetimidates, N-phenyl trifluoroacetimidates, thioglycosides, sulfoxides, heteroaryl thioglycosides, 1-hydroxyl sugars, 1-O-acetates, and ortho-alkynylbenzoates. Each synthesis is depicted starting from the O-glycosylation of the aglycone (or its precursor); the glycosylation conditions and outcomes (yields and stereoselectivities) are discussed, and the subsequent transformations toward the final target, including the elongation of the glycan, the elaboration of the aglycone, and the protecting group manipulations are also given in detail.

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Total Synthesis and Stereochemical Reassignment of Mandelalide A

Cited by 81 publications

References 41 publications

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors

New Mandelalides Expand a Macrolide Series of Mitochondrial Inhibitors

Computational Chemistry to the Rescue: Modern Toolboxes for the Assignment of Complex Molecules by GIAO NMR Calculations

O-Glycosylation methods in the total synthesis of complex natural glycosides

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