3102-57-6

Usage

Biological Activity

A potent modulator of cell proliferation and differentiation. Activates protein phosphatase-1 (PP1) and -2A (PP2A), as well as ceramide-activated protein phosphatase (CAPP) in vitro .

Biochem/physiol Actions

Cell-permeable, biologically active ceramide. It induces differentiation and apoptosis in cells and has been shown to activate protein phosphatases.

References

1) Minano et al. (2008), C2-ceramide mediates cerebellar granule cells apoptosis by activation of caspases-2, -9, and -3; J. Neurosci. Res., 86 1734 2) Prinetti et al. (1997), Involvement of a ceramide activated protein phosphatase in the differentiation of neuroblastoma Neuro2a cells; FEBS Lett., 414 475 3) Zhang et al. (1997), Kinase suppressor of Ras is ceramide-activated protein kinase; Cell, 89 63 4) Matsuzaka et al. (2016) Characterization and Functional Analysis of Extracellular Vesicles and Muscle-Abundant miRNAs (miR-1, miR-133a, and miR-206) in C2C12 Myocytes and mdx Mice; PLoS One 11(12) e0167811 [Focus Biomolecules Citation] 5) Matsuzaka et al. (2016) Characterization and functional analysis of extracellular vesicles and muscle-abundant miRNA in C2C12 myocytes and Mdx mice; PLoS One 11(12) e0167811 [Focus Biomolecules Citation]

InChI:InChI=1/C20H39NO3/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-20(24)19(17-22)21-18(2)23/h15-16,19-20,22,24H,3-14,17H2,1-2H3,(H,21,23)/b16-15+/t19-,20+/m0/s1

Upstream product

• 108-24-7 acetic anhydride 
• 123-78-4 (2S,3R,4E)-2-amino-4-octadecene-1,3-diol 
• 75-36-5 acetyl chloride 
• 114697-01-7 (+/-)-N-(4t-pentadec-1-ynyl-2r-phenyl-[1,3]dioxan-5t-yl)-acetamide 
• 114697-01-7 (+/-)-N-(4c-pentadec-1-ynyl-2r-phenyl-[1,3]dioxan-5c-yl)-acetamide 
• 94676-99-0 N-((1RS,2RS)-2-hydroxy-1-hydroxymethyl-heptadec-3-ynyl)-acetamide 
• 2482-37-3 (+/-)-erythro-1,3-diacetoxy-2-acetylamino-octadec-4c-ene 
• 94676-99-0 N-((1RS,2SR)-2-hydroxy-1-hydroxymethyl-heptadec-3-ynyl)-acetamide 
• 72-89-9 acetylcoenzyme A 
• 221455-36-3 tert-butyl ((2S,3R,E)-1-((tert-butyldimethylsilyl)oxy)-3-hydroxy-octadec-4-en-2-yl)carbamate 
• 116467-63-1 N-tert-butyloxycarbonylsphingosine 
• 117487-53-3 tert-butyl (1S,2R)-N-<2-hydroxy-1-(hydroxymethyl)-3-heptadecynyl>carbamate 
• 115464-01-2 (4S,1'R)-4-(1'-Hydroxy-2'-hexadecinyl)-2,2-dimethyl-3-oxazolidincarbonsaeure-tert-butylester 
• 2673-72-5 (2S,3R,E)-2-aminooctadec-4-ene-1,3-diol hydrochloride 

Downstream Products

• 2482-37-3 (2S,3R,4E)-2-acetamido-1,3-diacetoxyoctadec-4-ene 
• 2482-37-3 (+/-)-threo-1,3-diacetoxy-2-acetylamino-octadec-4c-ene 
• 2482-37-3 (+/-)-erythro-1,3-diacetoxy-2-acetylamino-octadec-4c-ene 
• 123-78-4 (2S,3R,4E)-2-amino-4-octadecene-1,3-diol 
• 13031-64-6 (2S,3R)-2-acetylaminooctadecan-1,3-diol 

Relevant academic research and scientific papers

N-AS-triggered SPMs are direct regulators of microglia in a model of Alzheimer’s disease

Sphingosine kinase1 (SphK1) is an acetyl-CoA dependent acetyltransferase which acts on cyclooxygenase2 (COX2) in neurons in a model of Alzheimer’s disease (AD). However, the mechanism underlying this activity was unexplored. Here we show that N-acetyl sphingosine (N-AS) is first generated by acetyl-CoA and sphingosine through SphK1. N-AS then acetylates serine 565 (S565) of COX2, and the N-AS-acetylated COX2 induces the production of specialized pro-resolving mediators (SPMs). In a mouse model of AD, microglia show a reduction in N-AS generation, leading to decreased acetyl-S565 COX2 and SPM production. Treatment with N-AS increases acetylated COX2 and N-AS-triggered SPMs in microglia of AD mice, leading to resolution of neuroinflammation, an increase in microglial phagocytosis, and improved memory. Taken together, these results identify a role of N-AS in the dysfunction of microglia in AD.

Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase

Enantiomers or diastereomers of chiral bioactive compounds often exhibit different biological and toxicological properties. Here, we report the efficient synthesis of four stereoisomers of sphingosine and derivatization of unique chiral ceramides through a combinatorial chemistry by solid-phase activated resin ester. In addition, to test the effectivity of stereochemistry of ceramide, we demonstrated a cell-based assay of sphingomyelin synthase inhibition in the presence ofchiral unique ceramides, which suggested that libraries of this sort will be a rich source of biologically active synthetic molecules.

Ceramide compound and application

The invention relates to a ceramide compound; in the structural general formula, m=2-12; n=0-20. The ceramide compound has significant pseudo neural growth factor activity, and is the small molecule compound capable of passing through blood-brain barrier. The structural general formula is shown as Figure.

Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity

A polymer-supported route for the synthesis of sphingosine derivatives is presented based on the C-acylation of polymeric phosphoranylidene acetates with an Fmoc-protected amino acid. The approach enables the flexible variation of the sphingosine tail through a deprotection-decarboxylation sequence followed by E-selective Wittig olefination cleavage. d-Erythro-sphingosine analogs have been synthesized by diastereoselective reduction of the keto group employing LiAlH(O-tBu)3as reducing agent. The effect of ceramides and keto-ceramides on the proliferation of three cancer cell lines HEP G-2, PC-12 and HL-60 was investigated and a ceramide containing an aromatic sphingosine tail was identified as being most active.

Exploring Leishmania major Inositol Phosphorylceramide Synthase (LmjIPCS): Insights into the ceramide binding domain

The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C13) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.

Inhibitory activity of a ceramide library on interleukin-4 production from activated T cells

Allergic diseases are hypersensitivity disorders associated with the production of specific immunoglobulin E (IgE) to environmental allergens. Interleukin (IL)-4, produced primarily by CD4+ T cells, is an important stimulus for the switch of th

Sphingomyelin analogues as inhibitors of sphingomyelinase

To search for neutral sphingomyelinase inhibitors we designed and synthesized hydrolytically stable analogues of sphingomyelin. The novel compounds 8 and 9 which were replaced the phosphodiester moiety of sphingomyelin with the carbamate moiety showed inhibitory activity with an IC50 value of μM on neutral sphingomyelinase in rat brain microsomes. Compound 8i showed a selective neutral sphingomyelinase inhibitory activity.

The synthesis and biological characterization of a ceramide library

A facile synthesis of a combinatorial ceramide library and their activities in the NF-κB pathway and in apoptosis induction/prevention were demonstrated. A novel NF-κB activating molecule was discovered among ceramide containing β-galactose, and the structural requirements of ceramides for apoptosis induction was elucidated. Copyright

Formation of high-axial-ratio-microstructures from natural and synthetic sphingolipids

Amphiphiles that form high-axial-ratio-microstructures (HARMs) are being considered as novel materials for controlled release of drugs and other biologically functional molecules. HARMs consisting of tubules, ribbons, solid rods and helices are formed from sphingolipids by addition of water to a solution of amphiphile in DMF. Single molecular species of galactocerebroside (GalCer) containing long unsaturated fatty acid chains or natural GalCer containing mixed-length, non-hydroxy fatty acids (NFA-GalCer) or α-hydroxy fatty acids (HFA-GalCer) form cylindrical structures. In contrast, single molecular species of GalCer containing long saturated fatty acids form ribbons and helices. GalCer HARMs are typically under 100 nm in diameter and have lengths of several microns. The importance of the amide of GalCer for HARM formation was evaluated using psychosine, which forms solid fibers, whereas sphingosine and an analog of GalCer in which the amide is reduced to a secondary amine form amorphous aggregates. Single molecular species of ceramide containing long unsaturated fatty acid chains form cylindrical structures, whereas those with long saturated fatty acids form ribbons and helices. Short chain saturated ceramide also forms cylindrical structures. GalCer analogs with N-acetyl-glycine in place of the galactose form fibers whereas those with N-acetyl-proline yield amorphous material. The N-acetyl-proline-containing amphiphile can de doped into pure GalCer or NFA-GalCer without perturbing tubule formation.

Improved, gram scale synthesis of N,O,O-triacetyl-erythro- and threo-C18-sphingosines from serine

A formal total synthesis of all four (E)C18-sphingosine stereoisomers from serine has been carried out. This involves the thiazole-based homologation of the amino acid into a chiral 3-amino-2,4-dihydroxybutanal 1 and the Wittig olefination of 1 with the ylide from the C14 alkyl phosphonium salt 2. The photoisomerization of the resulting mixture of Z- and E-alkenes affords the target sphingosine. Thus, N,O,O-triacetyl-D-erythro C18-sphingosine 5 and the L-threo isomer 10 were prepared in 43-44% overall yield from the aldehyde (S,S)-1a and (2R,3S)-1b, respectively. The corresponding antipodal L-erythro and D-threo isomers can be prepared in the same way starting from aldehydes ent-1a and ent-1b, respectively. Conversion of the above acetyl sphingosines into the free sphingoid bases has been reported in the literature.