252039-52-4

Upstream product

• 14464-32-5 stearic acid N-hydroxysuccinimide ester 
• 123-78-4 (2S,3R,4E)-2-amino-4-octadecene-1,3-diol 
• 116467-63-1 N-tert-butyloxycarbonylsphingosine 
• 58909-84-5 sphingomyelin 
• 57-11-4 stearic acid 
• 14617-86-8 4-nitrophenyl stearate 
• 56776-02-4 N-hydroxysuccinimide ester of stearic acid 
• 112-76-5 Stearoyl chloride 
• 432038-17-0 5-(tert-butyl-dimethyl-silanyl)-2-(tert-butyl-dimethyl-silanyloxy)-octadec-4-ene-1,3-diol 
• 765-13-9 pentadec-1-yne 
• 104826-27-9 <2(R),3(R),4E>-1,3-O-isopropylidene-4-octadecene-1,2,3-triol 
• 104826-36-0 <2(S),3(R),4Z>-1,3-O-isopropylidene-2-octadecanamido-4-octadecene-1,3-diol 
• 147910-01-8 (2S,3R,4Z)-3-(benzyloxymethoxy)-1-(tert-butyldimethylsiloxy)-2-(octadecanoylamino)-4-octadecene 
• 104826-34-8 <2(S),3(R),4Z>-2-amino-1,3-O-isopropylidene-4-octadecene-1,3-diol 

Downstream Products

• 36271-49-5 (2S,3R,4E)-1-(β-D-galactopyranosyloxy)-2-(octadecanoylamino)-3-hydroxyoctadec-4-ene 

Relevant academic research and scientific papers

Effect of laser and LED on enzymatic production of ceramide

An enzyme (Phospholipase C Type I from Clostridium perfringens) was exposed to 0-810 J cm-2 of energy using laser light at wavelengths 808, 532, 1064 and 1342 nm and two LED light sources at wavelengths 810 and 640 nm. Enzyme responses were evaluated by measuring ceramide concentration using high performance thin-layer chromatography (HPTLC) at 0.5, 1, 2, 3, 4, 6, 17, 24 h after irradiation. The duration of effect was evaluated from the experimental data. The results show that enzyme activity can be increased by using both laser and LED sources whose wavelength is located within a certain range. The effect depends on the energy and wavelength of the light. The increase in enzyme activity continued for about 4 h after irradiation. This study shows that the duration of irradiation should be included as one of the main laser parameters when reporting on the effects of laser irradiation on enzymes. We also find that laser sources and LED sources have the same effect on enzyme activity if the wavelength and absorbed energy are equal. 2010 Tianjin Medical University. Photochemistry and Photobiology

Total synthesis of ceramides and β-O-glucosylceramides via intramolecular fatty acyl group migration

Acyl migration of alkyl and aromatic acyl groups from an alcohol to another alcohol or amine is a phenomenon that occurs in nature and can be a bane to some synthetic strategies. An acyl migration-dependent method was developed for the synthesis of ceramide and glucosyl ceramide derivatives, in which the desired fatty acyl moiety acts both as protecting and migrating group. Removal of the tetrachlorophthalimido (TCP) group with ethylenediamine as a mild base at room temperature resulted in subsequent intramolecular fatty acyl group migration from -O to -N, on sphingosine or per acetylated glucosyl sphingosine to yield the desired N-acylated products. Deacetylation reaction afforded the desired β-O-glucosylceramide derivatives. Thus, choice of the appropriate blocking group turns acyl migration into a tool for synthesis, rather than an impediment.

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.

Design and synthesis of sphingomyelin-cholesterol conjugates and their formation of ordered membranes

A lipid raft is a cholesterol (Chol)-rich microdomain floating in a sea of lipid bilayers. Although Chol is thought to interact preferentially with sphingolipids such as sphingomyelin (SM), rather than with glycerophospholipids, the origin of the specific interaction has remained unresolved, primarily because of the high mobility of lipid molecules and weak intermolecular interactions. In this study, we synthesized SM-Chol conjugates with functionally designed linker portions to restrain Chol mobility and examined their formation of ordered membranes by a detergent insolubility assay, fluorescence anisotropy experiments, and fluorescence-quenching assay. In all of the tests, membranes prepared from the conjugates showed properties of ordered domains comparable to a SM-Chol (1:1) membrane. To gain insight into the structure of bilayers composed from the conjugates, we performed molecular dynamics simulations with 64 molecules of the conjugates, which suggested that the conjugates form a stable bilayer structure by bending at the linker portion and, mostly, reproduce the hydrogen bonds between the SM and Chol portions. These results imply that the molecular recognition between SM and Chol in an ordered domain is essentially reproduced by the conjugated molecules and, thus, demonstrates that these conjugate molecules could potentially serve as molecular probes for understanding molecular recognition in lipid rafts.

Design and synthesis of caged ceramide: UV-responsive ceramide releasing system based on UV-induced amide bond cleavage followed by O-N acyl transfer

Sphingolipids, recognized as membrane constructs and as key signaling molecules, have been studied to examine intracellular function. Some caged sphingolipids that release parent sphingolipids after exposure to UV-irradiation have been previously developed, but caged ceramide has yet to be reported. In this study, we report the design and synthesis of a caged ceramide. Photo-irradiation experiment clarified that the caged ceramide can be successfully converted to the parent ceramide by UV-irradiation. Introduction of an alkyne-handle moiety for further modification of the caged ceramide is also reported.

Imaging of enzyme replacement therapy using PET

Direct enzyme replacement therapy (ERT) has been introduced as a means to treat a number of rare, complex genetic conditions associated with lysosomal dysfunction. Gaucher disease was the first for which this therapy was applied and remains the prototypical example. Although ERT using recombinant lysosomal enzymes has been shown to be effective in altering the clinical course of Gaucher disease, Fabry disease, Hurler syndrome, Hunter syndrome, Maroteaux-Lamy syndrome, and Pompe disease, the recalcitrance of certain disease manifestations underscores important unanswered questions related to dosing regimes, tissue half-life of the recombinant enzyme and the ability of intravenously administered enzyme to reach critical sites of known disease pathology.We have developed an innovative method for tagging acid β-glucocerebrosidase (GCase), the recombinant enzyme formulated in Cerezyme used to treat Gaucher disease, using an 18F-labeled substrate analogue that becomes trapped within the active site of the enzyme. Using micro-PET we show that the tissue distribution of injected enzyme can be imaged in a murine model and that the PET data correlate with tissue 18F counts. Further we show that PET imaging readily monitors pharmacokinetic changes effected by receptor blocking. The ability to 18F-label GCase to monitor the enzyme distribution and tissue half-life in vivo by PET provides a powerful research tool with an immediate clinical application to Gaucher disease and a clear path for application to other ERTs.

Highly efficient and stereoselective synthesis of β-glycolipids

β-Galactosylceramide and glycolipid analogues were prepared in high yield and with complete chemo and stereoselectivity by reaction of α-iodo glycosides with stannyl ceramides, formed in situ. TBAI was used to activate both the iodogalactose and the stannyl ether. The Royal Society of Chemistry 2008.

ONE-POT SYNTHESIS OF ALPHA/BETA-O-GLYCOLIPIDS

The present invention provides a one-pot method of preparing an unprotected α-O-glycolipid. The first step involves contacting a protected α-iodo sugar with a catalyst and a lipid comprising a hydroxy group, under conditions sufficient to prepare a protected α- O-glycolipid. The second step involves deprotecting the protected α-O-glycolipid under conditions sufficient to prepare the unprotected α-O-glycolipid, wherein the contacting and deprotecting steps are performed in a single vessel. The present invention also provides a one-pot method of preparing an unprotected β-O-glycolipid following the steps for the preparation of the unprotected α-O-glycolipid.

Efficient, one-pot syntheses of biologically active α-linked glycolipids

Per-O-silylated galactosyl iodides undergo α-glycosidation with fully functionalized glycolipids producing biologically relevant conjugates. The Royal Society of Chemistry.