Two-directional total synthesis of efomycine M and formal total synthesis of elaiolide

Barth, Roland; Mulzer, Johann

doi:10.1016/j.tet.2008.01.114

Cited by 18 publications

(8 citation statements)

References 43 publications

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“…After selective hydrolysis of the less hindered methyl ester and TBS‐group removal by the Olah reagent, the so‐obtained seco acid 12 was cyclized by Yamaguchi macrolactonization to give macrodiolide 13 in excellent (80 %) yield. Next, we used the Wacker oxidation of both allyl groups to reveal the side chain ketone functionalities [50] . The optimized conditions utilized 0.4 equivalents of PdCl 2 and 0.4 equivalents of Cu(OAc) 2 under 1 atmosphere of O 2 , while higher Cu(OAc) 2 loading led to oxidative deprotection of the PMB group.…”

Section: Resultsmentioning

confidence: 99%

Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS‐STING Pathway

et al. 2021

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The development of new immunomodulatory agents can impact various areas of medicine. In particular, compounds with the ability to modulate innate immunological pathways hold significant unexplored potential. Herein, we report a modular synthetic approach to the macrodiolide natural product (−)‐vermiculine, an agent previously shown to possess diverse biological effects, including cytotoxic and immunosuppressive activity. The synthesis allows for a high degree of flexibility in modifying the macrocyclic framework, including the formation of all possible stereoisomers. In total, 18 analogues were prepared. Two analogues with minor structural modifications showed clearly enhanced cancer cell line selectivity and reduced toxicity. Moreover, these compounds possessed broad inhibitory activity against innate immunological pathways in human PBMCs, including the DNA‐sensing cGAS‐STING pathway. Initial mechanistic characterization suggests a surprising impairment of the STING‐TBK1 interaction.

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Section: Resultsmentioning

confidence: 99%

Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS‐STING Pathway

et al. 2021

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“…This mode of action is still unclear, since one study questioned this mechanism [377] while another study supported it [378]. Later, the total synthesis of efomycin M was published [379].…”

Section: Non-carbohydrate Inhibitorsmentioning

confidence: 99%

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

2020

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Selectins belong to a group of adhesion molecules that fulfill an essential role in immune and inflammatory responses and tissue healing. Selectins are glycoproteins that decode the information carried by glycan structures, and non-covalent interactions of selectins with these glycan structures mediate biological processes. The sialylated and fucosylated tetrasaccharide sLex is an essential glycan recognized by selectins. Several glycosyltransferases are responsible for the biosynthesis of the sLex tetrasaccharide. Selectins are involved in a sequence of interactions of circulated leukocytes with endothelial cells in the blood called the adhesion cascade. Recently, it has become evident that cancer cells utilize a similar adhesion cascade to promote metastases. However, like Dr. Jekyll and Mr. Hyde’s two faces, selectins also contribute to tissue destruction during some infections and inflammatory diseases. The most prominent function of selectins is associated with the initial stage of the leukocyte adhesion cascade, in which selectin binding enables tethering and rolling. The first adhesive event occurs through specific non-covalent interactions between selectins and their ligands, with glycans functioning as an interface between leukocytes or cancer cells and the endothelium. Targeting these interactions remains a principal strategy aimed at developing new therapies for the treatment of immune and inflammatory disorders and cancer. In this review, we will survey the significant contributions to and the current status of the understanding of the structure of selectins and the role of selectins in various biological processes. The potential of selectins and their ligands as therapeutic targets in chronic and acute inflammatory diseases and cancer will also be discussed. We will emphasize the structural characteristic of selectins and the catalytic mechanisms of glycosyltransferases involved in the biosynthesis of glycan recognition determinants. Furthermore, recent achievements in the synthesis of selectin inhibitors will be reviewed with a focus on the various strategies used for the development of glycosyltransferase inhibitors, including substrate analog inhibitors and transition state analog inhibitors, which are based on knowledge of the catalytic mechanism.

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“…We will continue this work in the future by a quantitative calculation. [60] A quantitative characterization based on computed physicochemical property profiles such as Polarizability [29], Partition Coefficient (log P) [30][31][32][33], Hydration Energy [34][35][36], Molecular Volume [37], Molecular Surface and Molecular Mass [38] has been conducted. The physicochemical parameters used in the study are described below.…”

Section: Study Of Structure -Activity Relationships For 16-memberementioning

confidence: 99%

“…Based on our conclusions on the effect of substitution on Macrodiolides molecules, we chose a series of Macrodiolides derivatives; some of them have a biological activity [52][53][54][55][56][57][58][59][60]. Initially, we performed a structural comparison of this series Figure 4.…”

Section: Structural Comparison Of the 16-membered Macrodiolidesmentioning

confidence: 99%

Conformational Analysis, Substituent Effect and Structure Activity Relationships of 16-Membered Macrodiolides

Mazri

Belaidi

Kerassa

et al. 2014

ILCPA

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Electronic structures, Conformational Analysis, effect of the substitution and structure activity Relationships for macrodiolides, have been studied by PM3 and ab initio methods. In the present work, the calculated values, namely net charges, bond lengths, MESP, dipole moments, electronaffinities, heats of formation, drug-likeness and QSAR properties, are reported and discussed in terms of the biological activity of macrodiolides.

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Two-directional total synthesis of efomycine M and formal total synthesis of elaiolide

Cited by 18 publications

References 43 publications

Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS‐STING Pathway

Macrodiolide Diversification Reveals Broad Immunosuppressive Activity That Impairs the cGAS‐STING Pathway

Selectins—The Two Dr. Jekyll and Mr. Hyde Faces of Adhesion Molecules—A Review

Conformational Analysis, Substituent Effect and Structure Activity Relationships of 16-Membered Macrodiolides

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