- Total synthesis of ceramides and β-O-glucosylceramides via intramolecular fatty acyl group migration
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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.
- Gorantla, Jaggaiah N.,Hua, Yanling,Ketudat Cairns, James R.,Santhi, Maniganda
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p. 3270 - 3276
(2022/02/21)
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- COSMETIC COMPOSITION FOR SKIN IMPROVEMENT COMPRISING GREEN BARLEY EXTRACT
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Provided is a cosmetic composition for skin improvement including a green barley extract.
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- Chiral combinatorial preparation and biological evaluation of unique ceramides for inhibition of sphingomyelin synthase
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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.
- Koolath, Sajeer,Monde, Kenji,Murai, Yuta,Suga, Yoshiko
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supporting information
(2020/02/04)
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- Traceless synthesis of ceramides in living cells reveals saturation-dependent apoptotic effects
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Mammalian cells synthesize thousands of distinct lipids, yet the function of many of these lipid species is unknown. Ceramides, a class of sphingolipid, are implicated in several cell-signaling pathways but poor cell permeability and lack of selectivity in endogenous synthesis pathways have hampered direct study of their effects. Here we report a strategy that overcomes the inherent biological limitations of ceramide delivery by chemoselectively ligating lipid precursors in vivo to yield natural ceramides in a traceless manner. Using this method, we uncovered the apoptotic effects of several ceramide species and observed differences in their apoptotic activity based on acyl-chain saturation. Additionally, we demonstrate spatiotemporally controlled ceramide synthesis in live cells through photoinitiated lipid ligation. Our in situ lipid ligation approach addresses the long-standing problem of lipid-specific delivery and enables the direct study of unique ceramide species in live cells.
- Rudd, Andrew K.,Devaraj, Neal K.
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p. 7485 - 7490
(2018/07/25)
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- NOVEL SYNTHESIS INTERMEDIATES FOR OBTAINING DERIVATIVES OF SPHINGOSINES, CERAMIDES AND SPHINGOMYELINS WITH GOOD YIELDS
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The subject matter of the present invention is the novel molecules of formulae E, E′ and F. These molecules prove to be synthesis intermediates that are very advantageous for the manufacture of derivatives of sphingosine or of ceramides functionalized in position 1, with good yields, in which R1 and R2 are fatty chains, R3 is an alkyl group and R4 is a protective group for alcohol functions. Another subject of the invention is the use of the intermediates of type F for converting same into intermediates of type G, by means of reduction in the presence of lithium borohydride. The G molecules are precursors that are known to make it possible to obtain sphingolipids or sphingomyelin.
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Paragraph 0091; 0092
(2016/04/19)
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- POLYSACCHARIDE ANTIGEN-GLYCOLIPID CONJUGATE VACCINES
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The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines. The new vaccines consist of a multi-modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
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- Synthesis of a panel of carbon-13-labelled (glyco)sphingolipids
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The synthesis of a focussed library of sphingolipids differing in the number and position of 13C labels is described. The synthesised sphingolipids differ in substitution at both the sphingosine amine (either palmitoylated or unmodified) and the sphingosine primary hydroxyl (unmodified or glycosylated). Moreover, 13C atoms are incorporated into either the sphingosine or the palmitate moiety, or both. This set of compounds is intended for use in relative quantitative lipidomics studies to gain insight into sphingolipid metabolism in healthy and diseased (lysosomal storage disorders) patients and animal models. The synthesis of a focussed library of sphingolipids differing in the number and position of 13C labels is described. 13C atoms are incorporated into either the sphingosine or the palmitate moiety, or both. This set of compounds is intended for use in relative quantitative lipidomics studies to gain insight into sphingolipid metabolism.
- Wisse, Patrick,Gold, Henrik,Mirzaian, Mina,Ferraz, Maria J.,Lutteke, Ginger,Van Den Berg, Richard J. B. H. N.,Van Den Elst, Hans,Lugtenburg, Johan,Van Der Marel, Gijsbert A.,Aerts, Johannes M. F. G.,Codée, Jeroen D. C.,Overkleeft, Herman S.
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p. 2661 - 2677
(2015/04/27)
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- Synthesis of α-l-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies
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An α-l-rhamnosyl ceramide (1, α-l-RhaCer) has been prepared that was recognized by anti-l-rhamnose (anti-Rha) antibodies. During these studies we explored the use of an α-l-rhamnosyl thioglycoside and a trichloroacetimidate as a glycosyl donors. Subsequently, the acceptors desired for glycosylation, 3-O-benzoylazidosphingosine or 3-O-alloxycarbonylsphingosine, were prepared from d-xylose. The thioglycoside donor, 2,3,4-tri-O-acetyl-1-(4-tolyl)thio-α-l-rhamnopyranoside, and the trichloroacetimidate donor, 2,3,4-tri-O-acetyl-1-(2,2,2-trichloroethanimidate)-α-l-rhamnopyranoside, were synthesized in 50% and 78% yield overall, respectively. The synthesis of the glycosylation acceptor employed an addition-fragmentation olefination that was successfully carried out in 53% yield. With the successful synthesis of key intermediates, α-l-RhaCer (1) was prepared without any insurmountable obstacles. Anti-Rha antibodies were prepared in BALB/c mice by immunizing them with rhamnose-ovalbumin (Rha-Ova) with Sigma Adjuvant System (SAS) and the anti-l-Rha antibodies were isolated from the blood sera. Liposomes and EL4 tumor cells were used as model systems to demonstrate the ability of 1 to insert into a lipid bilayer. The interaction of the liposomes or the EL4 cells with α-l-RhaCer (1) and anti-Rha antibodies were investigated by fluorescence microscopy and flow cytometry, respectively, to confirm the ability of glycolipid 1 to be displayed on the tumor cell surface as well as the ability to be recognized by anti-Rha antibodies.
- Long, David E.,Karmakar, Partha,Wall, Katherine A.,Sucheck, Steven J.
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p. 5279 - 5289
(2014/12/11)
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- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
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The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides.
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Paragraph 0294-0296
(2014/09/30)
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- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
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The present invention includes methods for the synthesis of sphingomyelins and dihydrosphingomyelins. The present invention also includes methods for the synthesis of sphingosines and dihydrosphingosines. The present invention further includes methods for the synthesis of ceramides and dihydroceramides.
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Paragraph 00245; 00246
(2014/09/29)
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- Sphingomyelin analogues and a process for preparation thereof
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A sphingomyelin analog represented by the following formula wherein R1 is C1-20 alkyl group, R2 is C1-20 alkyl group, aryl group or C1-6 alkyl group substituted by aryl group, and Z is photoaffinity-l
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Page/Page column 5
(2010/02/15)
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- SPHINGOLIPID-DERIVED PHARMACEUTICAL COMPOSITIONS
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The present invention relates to specific sphingolipids/sphingolipid derivatives as pharmaceutical compositions as well as their use in the preparation of medicaments for the treatment, prevention and/or amelioration of disorders relating to pathological processes in lipid rafts.
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- Versatile synthetic method for sphingolipids and functionalized sphingosine derivatives via olefin cross metathesis
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A highly efficient and versatile method for the synthesis of various sphingolipids, such as sphingomyelin, ceramide, sphingosine, sphingosine 1-phosphate, and functionalized sphingosine derivatives, was established by two types of combinations of the olefin cross metathesis reaction. One reaction was between the same olefin part and appropriate amino alcohols, which were prepared starting from N-Boc-L-serine, and the other was between appropriate olefins and the same amino alcohol.
- Yamamoto, Tetsuya,Hasegawa, Hiroko,Hakogi, Toshikazu,Katsumura, Shigeo
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p. 5569 - 5572
(2007/10/03)
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- Inhibitory activity of a ceramide library on interleukin-4 production from activated T cells
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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
- Park, Jin,Li, Qian,Chang, Young-Tae,Kim, Tae Sung
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p. 2589 - 2595
(2007/10/03)
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- Sphingolipid synthesis via olefin cross metathesis: Preparation of a differentially protected building block and application to the synthesis of D-erythro-ceramide
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(Equation Presented) The sphingolipid backbone is readily assembled by E-selective olefin cross metathesis of a suitable building block.
- Rai, Anand Narain,Basu, Amit
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p. 2861 - 2863
(2007/10/03)
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- The synthesis and biological characterization of a ceramide library
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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
- Chang, Young-Tae,Choi, Jaehwa,Ding, Sheng,Prieschl, Eva E.,Baumruker, Thomas,Lee, Jae-Mok,Chung, Sung-Kee,Schultz, Peter G.
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p. 1856 - 1857
(2007/10/03)
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- The total syntheses of D-erythro-sphingosine, N-palmitoylsphingosine (ceramide), and glucosylceramide (cerebroside) via an azidosphingosine analog
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The total synthesis of D-erythro-sphingosine (9) was performed by a chirospecific method starting from D-galactose via an azidosphingosine intermediate to give highly homogeneous ( > 99.9% C18:1) sphingosine base (9) which contained no observable olefin isomerization by product and was demonstrated to be optically pure by a novel method utilizing Mosher's acid. Ceramide (10) was prepared from this sphingosine (9) with highly homogeneous (99.8% C16:0) palmitic acid by two methods. The cerebroside glucosylceramide (23) was the next sphingolipid in this series to be synthesized in a highly homogeneous form. These three sphingolipids are currently being used for biophysical studies of the structures of their hydrated bio-molecular assemblies.
- Duclos Jr., Richard I
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p. 111 - 138
(2007/10/03)
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- Stereoselective Preparation of Ceramide and Its Skeleton Backbone Modified Analogues via Cyclic Thionocarbonate Intermediates Derived by Catalytic Asymmetric Dihydroxylation of α,β-Unsaturated Ester Precursors
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A novel and efficient synthetic route to ceramide 1a and skeleton backbone modified ceramide analogues 1b,c is reported. The syntheses utilize osmium-catalyzed asymmetric dihydroxylation of (E)-α,β-unsaturated ester 5a-c as the chiral induction step, with the desired configurations in the products 1a-c, 2a, and 13 being generated by regioselective azide substitution at the α position of α,β-dihydroxyesters 6a-c via a cyclic thionocarbonate intermediate. Azido esters 10a-c are converted to the corresponding ceramides 1a-c by a sequence of azide reduction, N-acylation, ester reduction (NaBH4/LiBr), and Birch reduction of the triple bond (Li, EtNH2). These seven- to eight-step syntheses afford the target compounds 1a-c with excellent stereocontrol and in 30-42% overall yields. Furthermore, propargylic α-azido-β-hydroxyester 10a is converted to D-erythro-sphingosine 2a via simultaneous reduction of the triple bond, azido, and ester functional groups with LiAlH4, providing a highly concise and practical four-step synthesis of this key naturally occurring sphingolipid. The L-erythro stereoisomers are also available in high enantiomeric purity by the method described herein.
- He, Linli,Byun, Hoe-Sup,Bittman, Robert
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p. 7627 - 7633
(2007/10/03)
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- Stereoselective Synthesis of 2-Amino Alcohols by Use of an Isocyanide as an Aminomethylene Equivalent
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Preparation of an isocyanide having removable N-substituent and its application to the stereoselective synthesis of 2-amino alcohols are described. 4-(tert-Butyldimethylsiloxy)-2,6-xylyl isocyanide was prepared from commercially available 3,5-xylenol.The isocyanide underwent a samarium iodide-mediated coupling reaction with organic halides and carbonyl compounds.Reduction of the reaction mixture with NaBH4 selectively afforded anti 2-(arylamino) alcohols, which were then deprotected to the corresponding 2-(primary amino) alcohols via desilylation with TBAF followed by oxidation with DDQ.A ceramide was successfully synthesized by use of the present stereoselective synthetic method for 2-amino alcohols, demonstrating a new synthetic utility of the isocyanide as an aminomethylene equivalent.
- Murakami, Masahiro,Ito, Hajime,Ito, Yoshihiko
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p. 6766 - 6770
(2007/10/02)
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- Syntheses of two pairs of enantiomeric C18-sphingosines and a palmitoyl analogue of gaucher spleen glucocerebroside
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Sixteen kinds of chiral C4-epoxides [(-)-10a-d,(+)-10a-d,(-)-11a-d,(+)-11a-d], which are synthons in our synthetic strategy for complex lipids, have been prepared from (2Z)-2-butene-1,4-diol (6) by employing a Sharpless asymmetric epoxidation. By using the chiral C4-epoxides [(+)-10a,(-)-10a,(-)-11a,(+)-11a] as starting compounds, two pairs of enantiomeric (D-erythro, L-erythro, D-threo, and L-threo)-C18-sphingosines (1, 2, 3, 4) have been synthesized via a regioselective ring-opening of the epoxide ring with azide anion followed by reduction of the azide group to an amino group and a Wittig reaction. Furthermore, D-erythro-C18-sphingosine (1) has been converted to a palmitoyl analogue (5a) of Gaucher spleen glucocerebroside (5) through a reaction pathway including successive condensations with palmitic acid and D-glucose.
- Shibuya,Kawashima,Narita,Ikeda,Kitagawa
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p. 1154 - 1165
(2007/10/02)
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- SYNTHESES OF D-ERYTHRO-1-DEOXYDIHYDROCERAMIDE-1-SULFONIC ACID AND PHOSPHONOSPHINGOGLYCOLIPID FOUND IN MARINE ORGANISM VIA A COMMON PRECURSOR
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D-Erythro-1-deoxydihydroceramide-1-sulfonic acid, isolated from alkali-stable hydrogenated lipids in a non-photosynthetic marine diatom, Nitzschia alba, and (2S,3R)-N-palmitoyl-1-O--β-D-galactopyranosyl>-D-sphingosine, found in marine snail Turbo cornutus were synthesized via a common precursor (10) starting from galactose.
- Ohashi, Kinji,Kosai, Shunji,Arizuka, Mitsuo,Watanabe, Takashi,Yamagiwa, Yoshiro,et al.
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p. 2557 - 2570
(2007/10/02)
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- A New Route to Racemic erythro-Sphingosine and Ceramides. The 1,2-versus 1,4-Addition Reaction of Hexadec-2-enal with 2-Nitroethanol
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The reaction of hexadec-2-enal (5) with 2-nitroethanol (3) in triethylamine gave the 1,2-adducts (8) and (9), while the reaction in methanol-potassium carbonate gave the Michael adducts (6) and (7).Epimerization of the threo-acetonide (10) smoothly gave the erythro-acetonide (11), which gave the amino acetonide (12) on reduction.Phthaloylation, deacetalization, and deprotection of compound (12) gave rac-erythro-sphingosine (1).On the other hand, acylation and deacetalization of compound (12) gave the ceramide (16).
- Hino, Tohru,Nakakyama, Kiyoshi,Taniguchi, Mikio,Nakagawa, Masako
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p. 1687 - 1690
(2007/10/02)
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- A HIGHLY STEREOSELECTIVE SYNTHESIS OF 2(S),3(R),4E- AND 2(S),3(R),4Z-N-TETRACOSANOYLSPHINGENINE FROM D-GLUCOSE
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The synthesis of 4-E- and 4-Z-D-erythro-ceramide was achieved in 10 steps in ca. 20-30percent overall yield, starting from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose.E- and Z-5-Deoxy-1,2-O-isopropylidene-5-C-tetradecylidene-α-D-xylofuranose were used a
- Koike, Katsuya,Numata, Masaaki,Sugimoto, Mamoru,Nakahara, Yoshiaki,Ogawa, Tomoya
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p. 113 - 124
(2007/10/02)
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