N-Metallocenoylsphingosines as targeted ceramidase inhibitors: Syntheses and antitumoral effects

Rothemund, Matthias; Bär, Alexander; Klatt, Felix; Weidler, Sascha; Köhler, Leonhard H. F.; Unverzagt, Carlo; Kuhn, Claus-D.; Schobert, Rainer

doi:10.1016/j.bioorg.2020.103703

Cited by 6 publications

(11 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1 H NMR and 13 C NMR of sphingosines 10 using methanol‐ d 4 as solvent only show clearly the resonances for the protiated headgroup and double bond. These signals consist with that of the protiated sphingosines in literatures [21,24,26] . Interestingly, if the solvent for NMR is d ‐chloroform rather than methanol‐ d 4 , an apparent water peak appears in the 1 H NMR spectrum of sphingosine (see Figure S41).…”

Section: Resultsmentioning

confidence: 65%

“…This strategy has been widely applied to synthesize the protiated sphingosines by Yamanoi et al., [21] Lee et al., [22] Ghosh et al [23] . and Rothemund et al [24] …”

Section: Resultsmentioning

confidence: 99%

“…The preparation of phosphonate 6 was according to the procedure of Lee et al [22] . and Rothemund et al [24] . (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

“…In the formation of α, β‐unsaturated ketone via HWE coupling, the E / Z isomerism of the product depends on the basicity of phosphonate, which involved in the solvent polarity and the counterion for phosphonyl anion [25] . Counterion Li + and K + and solvent MeCN and THF are always used in HWE coupling to achieve a high E / Z stereoselectivity for the protiated sphingosines [17,22,24] . Byun et al [17] .…”

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Gram‐Scale Synthesis of Chain‐Deuterated Sphingosine and Its Derivatization to Produce Ceramide, Sphinganine and Sphingosine‐1‐phosphate

Wang

Song

et al. 2023

Eur J Org Chem

View full text Add to dashboard Cite

Sphingosine plays crucial roles in various cellular functions. Deuterated molecules are widely used as the important tools to explore the structure, property, and function of biochemical materials. We here report a gram-scale synthesis of sphingosines with different deuterated chains. The synthesis started from different protiated fatty acids, which underwent hydrothermal platinum-catalyzed hydrogen/deuterium (H/D) exchange to produce the deuterated chains with different length. The Horner-Wadsworth-Emmons (HWE) coupling of a chiral amino acid derivative with the deuterated chains generated the unsaturated ketone precursors. The following stereoselective reduction via cyclic Felkin-Anh transition led to the desired anti-amino alcohol geometry. This efficient protocol enabled the gram-scale synthesis of the chain-deuterated sphingosines. The subsequent synthesis of the chain-deuterated derivatives, i. e. ceramide, sphinganine and sphingosine-1-phosphate, is also described. Their deuterium content was simultaneously characterized by 1 H NMR and high-resolution mass spectrum (HRMS).

show abstract

Section: Resultsmentioning

confidence: 65%

“…This strategy has been widely applied to synthesize the protiated sphingosines by Yamanoi et al., [21] Lee et al., [22] Ghosh et al [23] . and Rothemund et al [24] …”

Section: Resultsmentioning

confidence: 99%

“…The preparation of phosphonate 6 was according to the procedure of Lee et al [22] . and Rothemund et al [24] . (Scheme 2).…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Gram‐Scale Synthesis of Chain‐Deuterated Sphingosine and Its Derivatization to Produce Ceramide, Sphinganine and Sphingosine‐1‐phosphate

Wang

Song

et al. 2023

Eur J Org Chem

View full text Add to dashboard Cite

show abstract

“…Moreover, tamoxifen has shown its ability to inhibit ASAH1 in polyploid giant cancer cells by reducing their division [ 140 ]. Recently, the synthesis of N-metallocenoylsphingosines has been described, demonstrating its cytotoxic capacity and inhibition of the cell cycle in cancer cells [ 141 ].…”

Section: Enzymes Of Ceramide Metabolismmentioning

confidence: 99%

Ceramide Metabolism Enzymes—Therapeutic Targets against Cancer

et al. 2021

View full text Add to dashboard Cite

Sphingolipids are both structural molecules that are essential for cell architecture and second messengers that are involved in numerous cell functions. Ceramide is the central hub of sphingolipid metabolism. In addition to being the precursor of complex sphingolipids, ceramides induce cell cycle arrest and promote cell death and inflammation. At least some of the enzymes involved in the regulation of sphingolipid metabolism are altered in carcinogenesis, and some are targets for anticancer drugs. A number of scientific reports have shown how alterations in sphingolipid pools can affect cell proliferation, survival and migration. Determination of sphingolipid levels and the regulation of the enzymes that are implicated in their metabolism is a key factor for developing novel therapeutic strategies or improving conventional therapies. The present review highlights the importance of bioactive sphingolipids and their regulatory enzymes as targets for therapeutic interventions with especial emphasis in carcinogenesis and cancer dissemination.

show abstract

Effective drug combinations of betulinic acid and ceranib-2 loaded Zn:MnO2 doped-polymeric nanocarriers against PC-3 prostate cancer cells

Tan

Danışman‐Kalındemirtaş

Karakuş

2023

Colloids and Surfaces B: Biointerfaces

View full text Add to dashboard Cite

N-Metallocenoylsphingosines as targeted ceramidase inhibitors: Syntheses and antitumoral effects

Cited by 6 publications

References 50 publications

Gram‐Scale Synthesis of Chain‐Deuterated Sphingosine and Its Derivatization to Produce Ceramide, Sphinganine and Sphingosine‐1‐phosphate

Gram‐Scale Synthesis of Chain‐Deuterated Sphingosine and Its Derivatization to Produce Ceramide, Sphinganine and Sphingosine‐1‐phosphate

Ceramide Metabolism Enzymes—Therapeutic Targets against Cancer

Effective drug combinations of betulinic acid and ceranib-2 loaded Zn:MnO2 doped-polymeric nanocarriers against PC-3 prostate cancer cells

Contact Info

Product

Resources

About