- 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.
- Gorantla, Jaggaiah N.,Hua, Yanling,Ketudat Cairns, James R.,Santhi, Maniganda
-
p. 3270 - 3276
(2022/02/21)
-
- 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.
- Koolath, Sajeer,Monde, Kenji,Murai, Yuta,Suga, Yoshiko
-
supporting information
(2020/02/04)
-
- 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.
- -
-
Paragraph 0036; 0040-0044
(2017/07/06)
-
- 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.
- Matsumori, Nobuaki,Tanada, Norio,Nozu, Kohei,Okazaki, Hiroki,Oishi, Tohru,Murata, Michio
-
p. 8568 - 8575
(2011/09/15)
-
- 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.
- Shigenaga, Akira,Hirakawa, Hiroko,Yamamoto, Jun,Ogura, Keiji,Denda, Masaya,Yamaguchi, Keiko,Tsuji, Daisuke,Itoh, Kohji,Otaka, Akira
-
experimental part
p. 3984 - 3990
(2011/06/25)
-
- 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.
- Morales-Serna, Jose Antonio,Boutureira, Omar,Diaz, Yolanda,Matheu, M. Isabel,Castillon, Sergio
-
supporting information; experimental part
p. 443 - 446
(2008/10/09)
-
- 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.
- -
-
Page/Page column 22
(2008/12/04)
-
- 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.
- Du, Wenjun,Kulkarni, Suvarn S.,Gervay-Hague, Jacquelyn
-
p. 2336 - 2338
(2008/02/09)
-
- Ganglioside GM3 derivatives with truncated ceramide moiety: Facial synthesis and inhibitory activity against KB cell growth
-
An expeditious sialylation reaction with phenylthioglycoside 4 as a sialyl donor and MeSOTf as a promoter was developed. These conditions are very useful for synthesizing ganglioside GM 3 (1), its C8-ceramide analog 2, and 3-deoxy analog 3 of 2 in an efficient manner. The GM 3 analog 2, whose hydrophilicity is increased by shortening the ceramide moiety, exhibits increased growth inhibiton of KB cells. The 3-hydoxy group of ceramide does not influence its activity against KB cells. Copyright Taylor & Francis Group, LLC.
- Kurosu, Michio,Kitagawa, Isao
-
p. 427 - 439
(2007/10/03)
-
- 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.
- Taguchi, Minoru,Sugimoto, Kikuo,Goda, Ken-Ichi,Akama, Tomoko,Yamamoto, Kyoko,Suzuki, Taizo,Tomishima, Yasumitsu,Nishiguchi, Mariko,Arai, Koshi,Takahashi, Kenzo,Kobori, Takeo
-
p. 1963 - 1966
(2007/10/03)
-
- Synthesis of D-erythro-sphingosine and D-erythro-ceramide.
-
A 1,2-metallate rearrangment of a higher order cuprate derived from an alpha-lithiated xylal derivative and tridecyllithium is the key step in a synthesis of D-erythro-sphingosine and ceramide. A convenient method for preparing alpha-lithiated glycals from alpha-phenylsulfinyl glycals is also described.
- Milne, Jacqueline E,Jarowicki, Krzysztof,Kocienski, Philip J,Alonso, Jorge
-
p. 426 - 427
(2007/10/03)
-
- 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
- Chang, Young-Tae,Choi, Jaehwa,Ding, Sheng,Prieschl, Eva E.,Baumruker, Thomas,Lee, Jae-Mok,Chung, Sung-Kee,Schultz, Peter G.
-
p. 1856 - 1857
(2007/10/03)
-
- Practical syntheses of [13C]- and [14C]-labelled glucosphingolipids
-
Synthetic routes to [glucose-U-14C]-1-O-(β-D-glucopyranosyl)-N-stearoyl-D-erythro-sp hingosine 1b and to [glucose-13C6]-1-O-(β-D-glucopyranosyl)sphingosine ([glucose-13C6]glucopsychosine, 2b) are described. Whereas the protected ceramide precursor for lb was prepared using conventional methodology, two new strategies were developed in the course of the synthesis of 2b. Of these, one relies on keeping a protecting group in place at all times to avoid the handling difficulties associated with sphingosine 4, while the other generates a protected derivative (24) of sphingosine indirectly by means of a Mitsunobu inversion.
- Duffin, Gordon R.,Ellames, George J.,Hartmann, Sascha,Herbert, John M.,Smith, David I.
-
p. 2237 - 2242
(2007/10/03)
-
- A facile stereoselective synthesis of sphingosine and ceramide
-
Flexible syntheses of sphingosine and ceramide were achieved by using D-xylose as the chiral pool and a CuCN-catalyzed allylic alkylation reaction of a dimesylate 8 for chain elongation with concomitant control of an E configuration of the double bond. VCH Verlagsgesellschaft mbH, 1996.
- Li, Yun-Long,Wu, Yu-Lin
-
p. 2079 - 2082
(2007/10/03)
-
- Structure-activity relationship of α-galactosylceramides against b16- bearing mice
-
Agelasphin-9b, (2S,3S,4R)-1-O-(α-D-galactopyranosyl)-16-methyl-2-[N- ((R)-2-hydroxytetracosanoyl)-amino]-1,3,4-heptadecanetriol, is a potent antitumor agent isolated from the marine sponge Agelas mauritianus. Various analogues of agelasphin-9b (a lead compound) were synthesized, and the relationship between their structures and biological activities was examined using several assay systems. From the results, KRN7000, (2S,3S,4R)-1-O-(α- D-galactopyranosyl)-2-(N-hexacosanoylamino)-1,3,4-octadecanetriol, was selected as a candidate for clinical application.
- Morita,Motoki,Akimoto,Natori,Sakai,Sawa,Yamaji,Koezuka,Kobayashi,Fukushima
-
p. 2176 - 2187
(2007/10/02)
-
- Biologically Active Glycosides from Asteroidea, XXX. Synthesis of An Optically Active Ceramide of GM1-Type Ganglioside from (+)-Diethyl L-Tatrtrate
-
A short total synthesis of the ceramide (2S,3R,4E))-2-(octadecanoylamino)-4-octadecene-1,3-diol (1) is reported, using (+)-diethyl L-tartrate (2) as the optically active starting material. Key Words: (+)-Diethyl L-tartrate / Ceramide / Sphingolipid / Enantioselective synthesis
- Metz, Katrin,Honda, Masanori,Komori, Tetsuya
-
-
- Synthesis and Spectral Properties of Chemically and Stereochemically Homogeneous Sphingomyelin and its Analogues
-
2-N-Stearoylspingosyl-1-phosphocholines of D-erythro (2S,3R) and L-threo (2S,3S) configurations and their phosphorothioyl analogues were obtained by a purely synthetic approarch using O-methyl-N,N-di-isopropylaminophosphorochloridite as the phosphitylating reagent for the formation of the phophodiester linkage.Final products were obtained pure in yields of 70-75 percent.The structure and the purity of synthesized compounds was determined using 1H, 13C, and 31P n.m.r. spectroscopy.With respect to the structure of the sphingosine long-chain base the synthetic D-erythro-SPM was found to be identical with the natural sphigomyelin from bovine brain whereas the semisynthetic N-palmitoylshingomyelin obtained via a deacylation-reacylation pathway comprises a mixture of D-erythro- and L-thero-SPM.The phosphorothioyl analogues of sphingomyelin synthesized by addition of elementar sulphur to intermediate phosphite were separated into individual diastereomers having opposite configuration at phosphorus.The absolute configurations of diastereomers at phosphorus were assigned based on the known stereospecifity of phospholipase C in the hydrolysis of phosphorothioyl analogues of phospholipids.1H N.m.r. data of synthesized compounds suggest that the configuration at C-3 of the sphingosine influences the average conformation of sphingomyelin with respect to the angle of rotation about the C(1)-C(2) bond.
- Bruzik, Karol S.
-
p. 423 - 432
(2007/10/02)
-
- Enantioselective Synthesis of D-erythro-Sphingosine and of Ceramide
-
The enynol 2 was transformed into D-erythro-sphingosine 11 (7 steps, 46 percent) and into ceramide 1 (8 step, 41 percent overall yield).The key steps were the mono-epoxidation of the enynol 5 (Ti(t-BuO)4, (-)-D-diethyl tartrate, t-BuOOH) to 6 (86percent, >/= 98percent ee), the regioselective intramolecular opening of the oxirane 6 via the benzylurethane 7, and the reductive transformation of the acetylene 9 into the oxazolidinone 10 (Li, EtNH2, 88 percent).
- Julina, Radomir,Herzig, Thomas,Bernet, Bruno,Vasella, Andrea
-
p. 368 - 373
(2007/10/02)
-
- A NOVEL ROUTE TO D-erythro-SPHINGOSINE AND RELATED COMPOUNDS FROM MONO-O-ISOPROPYLIDENE-D-XYLOSE OR -D-GALACTOSE
-
An efficient synthesis of D-erythro-sphingosine and -ceramide from D-xylose or D-galactose is described.A mixture of 2,4-O-isopropylidene-D-threose and its formate, which is available in one step from 3,5-O-isopropylidene-D-xylofuranose or 4,6-O-isopropylidene-D-galactopyranose, was subjected to the Wittig alkenation with triphenylphosphonio-tetra- and -hexa-decylid.The resulting 1,3-O-isopropylidenated C18 and C20 alkenes were each transformed, by introduction of an azido group at C-2, and selective reduction of the azide, into the corresponding 1,3-O-protected sphingosines that have the 2(S),3(R)-D-erythro configuration, from which a variety of ceramides were prepared by the sequence of N-acylation with the stearoyl or lignoceroyl group, and hydrolytic removal of the isopropylidene group.Some ceramides were also obtained by direct N-acylations of the corresponding sphingosines.
- Kiso, Makoto,Nakamura, Akemi,Tomita, Yoshimi,Hasegawa, Akira
-
p. 101 - 112
(2007/10/02)
-