- A simple and low cost synthesis of D-erythro-sphingosine and D-erythro-azidosphingosine from D-ribo-phytosphingosine: Glycosphingolipid precursors
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D-erythro-Sphingosine (1) and D-erythro-2-azidosphingosine (2) are both prepared from commercially available and cheap D-ribo-phytosphingosine (3) in a yield of 58% and 70%, respectively. A key transformation in the synthesis of D-erythro-sphingosine (1) is the palladium catalyzed regiospecific reduction of the Z-enol triflate 9. A crucial step in the synthesis of azidosphingosine 2 comprises a regio- and stereoselective in situ trans-elimination of the 4-O-triflate of azidophytosphingosine 13.
- Van Den Berg, Richard J.B.H.N.,Korevaar, Cornelis G.N.,Van Der Marel, Gijsbert A.,Overkleeft, Herman S.,Van Boom, Jacques H.
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- Studies on the inhibition of sphingosine-1-phosphate lyase by stabilized reaction intermediates and stereodefined azido phosphates
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Two kinds of inhibitors of the PLP-dependent enzyme sphingosine-1-phosphate lyase have been designed and tested on the bacterial (StS1PL) and the human (hS1PL) enzymes. Amino phosphates 1, 12, and 32, mimicking the intermediate aldimines of the catalytic process, were weak inhibitors on both enzyme sources. On the other hand, a series of stereodefined azido phosphates, resulting from the replacement of the amino group of the natural substrates with an azido group, afforded competitive inhibitors in the low micromolar range on both enzyme sources. This similar behavior represents an experimental evidence of the reported structural similarities for both enzymes at their active site level. Interestingly, the anti-isomers of the non-natural enantiomeric series where the most potent inhibitors on hS1PL.
- Sanllehí, Pol,Abad, José-Luís,Bujons, Jordi,Casas, Josefina,Delgado, Antonio
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- CD1a-binding glycosphingolipids stimulating human autoreactive T-cells: Synthesis of a family of sulfatides differing in the acyl chain moiety
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Native sulfatide (a mixture of 3-sulfated β-D-galactopyranosylceramides with different fatty acids at the ceramide moiety) is an antigen presented by CD1a proteins. Herein the preparation of four sulfatides, which are constituents of the natural mixture a
- Compostella, Federica,Franchini, Laura,De Libero, Gennaro,Palmisano, Giovanni,Ronchetti, Fiamma,Panza, Luigi
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- An Improved, Versatile, and Easily Scalable Synthesis of Sphingomyelins: Application to Stable Isotope Labeling
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With a view to make conveniently labeled mass spectrometry standards available, a set of deuterated sphingomyelins were prepared by a new expedient, flexible, robust, scalable, and high-yielding synthetic scheme starting from 2-azido-3- O -benzoylsphingos
- Blankenstein, J?rg,Le Strat, Franck,Pérard, Serge,Philippe, Nicolas,Roy, Sébastien
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- Synthesis of Gb3 Glycosphingolipids with Labeled Head Groups: Distribution in Phase-Separated Giant Unilamellar Vesicles
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The receptor lipid Gb3 is responsible for the specific internalization of Shiga toxin (STx) into cells. The head group of Gb3 defines the specificity of STx binding, and the backbone with different fatty acids is expected to influence its localization within membranes impacting membrane organization and protein internalization. To investigate this influence, a set of Gb3 glycosphingolipids labeled with a BODIPY fluorophore attached to the head group was synthesized. C24 fatty acids, saturated, unsaturated, α-hydroxylated derivatives, and a combination thereof, were attached to the sphingosine backbone. The synthetic Gb3 glycosphingolipids were reconstituted into coexisting liquid-ordered (lo)/liquid-disordered (ld) giant unilamellar vesicles (GUVs), and STx binding was verified by fluorescence microscopy. Gb3 with the C24:0 fatty acid partitioned mostly in the lo phase, while the unsaturated C24:1 fatty acid distributes more into the ld phase. The α-hydroxylation does not influence its partitioning.
- Sibold, Jeremias,Kettelhoit, Katharina,Vuong, Loan,Liu, Fangyuan,Werz, Daniel B.,Steinem, Claudia
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supporting information
p. 17805 - 17813
(2019/11/13)
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- D-erythro-sphingosine synthesis method
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The invention relates to a D-erythro-sphingosine synthesis method, comprising the steps of dissolving a compound 6 into dry tetrahydrofuran, adding lithium aluminum hydride under protection of nitrogen, after complete reaction of a raw material, adding a potassium sodium tartrate solution and finishing; extracting through ethyl acetate, concentrating and performing column chromatography; separating to obtain D-erythro-sphingosine. Compared with a traditional method, the synthesis method provided by the invention has the advantages that the use of a large amount of strong base phenyl lithium in a Wittig reaction process is avoided, meanwhile, the yield is increased; an azidation reaction adopts a two-step method of iodination and then azidation, and low temperature reaction in the existing technical scheme is not needed, so that the operation is more convenient and simple.
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Paragraph 0020; 0021; 0022; 0037; 0038
(2017/08/31)
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- One-pot syntheses of immunostimulatory glycolipids
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(Figure presented) Glycolipids containing α-linked galactosyl and glucosyl moieties have been shown to possess unique immunostimulatory activity creating a need for access to diverse and anomerically pure sources of these compounds for immunological studies. To meet this demand, glycosyl iodides were enlisted in the synthesis of these biologically relevant glycoconjugates. In the first-generation protocol, per-O-benzyl galactosyl iodide was efficiently coupled with activated sphingosine acceptors, but fully functionalized ceramides were found to be unreactive. To overcome this obstacle, per-O-trimethylsilyl glycosyl iodides were investigated and shown to undergo highly efficient coupling with ceramide and glycerol ester acceptors. Contrary to what has been observed with other donors, we detected little difference between the reactivity of glucosyl and galactosyl iodides. The trimethylsilyl protecting groups play a dual role in activating the donor toward nucleophilic attack while at the same time providing transient protection: the silyl groups are readily removed upon methanolysis. All reactions proceeded with complete acceptor regioselectivity, eliminating the need for additional protecting group manipulations, and the desired α-anomers were formed exclusively. This three-step, one-pot synthetic platform provides rapid access to an important class of immunostimulatory molecules including the first reported synthesis of the glucosyl analogue of the bacterial antigen BbGL-II.
- Schombs, Matthew,Park, Francine E.,Du, Wenjun,Kulkarni, Suvarn S.,Gervay-Hague, Jacquelyn
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scheme or table
p. 4891 - 4898
(2010/10/21)
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- Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry
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KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release a broad range of bioactive cytokines. In an effort to understand the structure-activity relationships, we have carried out synth
- Park, Jeong-Ju,Lee, Ji Hyung,Seo, Kyung-Chang,Bricard, Gabriel,Venkataswamy, Manjunatha M.,Porcelli, Steven A.,Chung, Sung-Kee
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supporting information; scheme or table
p. 814 - 818
(2010/06/16)
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- A modular synthesis of alkynyl-phosphocholine headgroups for labeling sphingomyelin and phosphatidylcholine
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(Figure Presented) A general route to phospho- and sphingolipids that incorporate an alkyne in the phosphocholine headgroup is described. The strategy preserves the ammonium functionality of the phosphocholine and can be easily modified to introduce desir
- Sandbhor, Mahendra S.,Key, Jessie A.,Strelkov, Ileana S.,Cairo, Christopher W.
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supporting information; experimental part
p. 8669 - 8674
(2010/02/28)
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- Efficient synthesis of D-erythro-sphingosine and D-erythro-azidosphingosine from D-ribo-phytosphingosine via a cyclic sulfate intermediate
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The synthesis of naturally occurring D-erythro-sphingosine and synthetically useful D-erythro-2-azidosphingosine from commercially available D-ribo-phytosphingosine is described. An important feature of this synthesis is the selective transformation of the 3,4-vicinal diol of phytosphingosine into the characteristic E-allylic alcohol of sphingosine via a cyclic sulfate intermediate.
- Kim, Sanghee,Lee, Sukjin,Lee, Taeho,Ko, Hyojin,Kim, Deukjoon
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p. 8661 - 8664
(2007/10/03)
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- HIGHLY EFFICIENT SYNTHESIS OF ALPHA-O-GALACTOSYL CERAMIDES
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A method for the production of a-O-galactosyl ceramide precursor is demonstrated. The method involves the reaction of galactosyl iodide with a sphingosine derivative or phytosphingosine derivative in the presence of a quaternary ammonium iodide salt to pr
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Page/Page column 13
(2008/06/13)
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- Efficient synthesis of α-galactosyl ceramide analogues using glycosyl iodide donors
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(Chemical Equation Presented) The combination of reactive galactosyl iodide donors with electron-rich acceptor lipids provides highly stereoselective and efficient routes to α GalCer analogues. Using per-O-silylated donors, key intermediates can be obtain
- Du, Wenjun,Gervay-Hague, Jacquelyn
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p. 2063 - 2065
(2007/10/03)
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- A process for the synthesis of sphingosine
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This invention relates to a method for the production of a sphingoid base according to formula comprising the steps of(1) dissolving a starting compound according to formula III or a salt thereof in a substantially inert solvent,(2) protecting the NH2 group with a NH2 protecting group,(3) activating C4 HR3' for an elimination reaction with C5HR4,(4) causing an elimination reaction to take place to form a double bond between the C4 and C5 carbon atom,(5) removing the NH2 protecting group.
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- Synthesis of D-erythro-sphingosine and D-erythro-ceramide.
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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
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p. 426 - 427
(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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- ω-Mercapto analogs of naturally occurring lipids
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Analogs of natural lipids, where one of the alkyl chains carries a terminal thiol functionality, were prepared by N- or O-acylation of sphingosine or monoacylglycerol derivatives, respectively, thus creating lipid mimics suitable for anchoring to e.g. gold surfaces.
- Ohlsson, Joergen,Magnusson, Goeran
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p. 2011 - 2014
(2007/10/03)
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- Chemoenzymatic Synthesis of All Four Stereoisomers of Sphingosine from Chlorobenzene: Glycosphingolipid Precursors
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Advantageous use of homochiral cyclohexadiene-cis-1,2-diol 2, available by means of biocatalytic oxidation of chlorobenzene with toluene dioxygenase, has enabled the synthesis of all four enantiomerically pure C18-sphingosines 1. The four requisite diastereomers of azido alcohols 4a-d were accessed by regioselective opening of epoxides 7 and 8 with either azide or halide ions. The configuration of C4 and C5 in azides 4 defines the stereochemistry of the incipient sphingosine chain, liberated from 4 by the oxidative cleavage of the C1-C6 olefin. For L-thereo-sphingosine (1b), lactol 20b generated by this cleavage was converted by periodate oxidation to azido deoxy L-threose 22b, which gave 1b upon Wittig olefination and reduction. Similarly, D-erythrosphingosine (1a) and L-erythro-sphingosine (1c) were generated from 4a,c, respectively. The last sphingosine (Id) was synthesized from the silyl-protected azido alcohol 29d. Subsequent transformations provided silyl-protected azido deoxy D-threose 32d, which upon Wittig olefmation and reduction gave D-threo-sphingosine (1d). Experimental and spectral data are provided for all new compounds.
- Nugent, Thomas C.,Hudlicky, Tomas
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p. 510 - 520
(2007/10/03)
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- An efficient stereoselective synthesis of sphingosine
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A stereocontrolled synthesis of D-(+)-erythro-sphingosine (1), starting from D-xylose as chiral pool material and employing the addition-fragmentation reaction of tosyl hydrazone of 2,3:4,5-di-O-isopropylidene-D-xylose as a key step for the chain extension with concomitant trans-selective C=C bond formation, is described.
- Kumar, Pradeep,Schmidt, Richard R.
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- Chemoenzymatic synthesis of D-erythro-C18- and L-threo-C18-sphingosines
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Biocatalytic conversion of chlorobenzene to the corresponding homochiral cyclohexadiene cis-diol allows, through careful symmetry-based planning, the stereodivergent synthesis of two sphingosine stereoisomers, the natural isomer 1 and the L-threo isomer 2, from selectively prepared diastereomers of azido alcohol 5.
- Hudlicky,Nugent,Griffith
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p. 7944 - 7946
(2007/10/02)
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- Stereoselective Synthesis of D(+)-erythro and L(-)-threo Sphingosines from Carbohydrates
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Stereocontrolled syntheses of D(+)-erythro and L(-)-threo shingosines are described starting from D-xylose and D-arabinose respectively through acetylenic intermediates 3 and 4, obtained by base induced double elimination of the β-alkoxy chlorides 5 and 13. Keywords: D(+)-erythro and L(-)-threo sphingosines; base induced double elimination reaction; acetylenic alcohol
- Yadav, J. S.,Vidyanand, D.,Rajagopal, D.
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p. 1191 - 1194
(2007/10/02)
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- An enantiospecific synthesis of D-erythro-sphingosine from D-tartaric acid
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An efficient enantiospecific synthesis of D-erythro-sphingosine (1) via azidosphingosine (2) is described, the absolute stereochemistry being derived from D-tartaric acid.
- Somfai, Peter,Olsson, Roger
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p. 6645 - 6650
(2007/10/02)
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- Process for the preparation of sphingosine derivatives
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The invention relates to a new process for the preparation of the sphingosine derivatives described in European Patent Application No. 146,810, of the formula: STR1 It comprises protecting D-galactose in the 4,6-position and oxidizing it to the corresponding D-threose protected in the 2,4-position, condensing an aliphatic chain (R3) onto the latter by a Wittig reaction, converting the free hydroxyl group into a azido group and splitting off the protective group, protecting the resulting 2-azido-1,3-dihydroxy compound selectively in the 1-position and blocking it in the 3-position, liberating the 1-hydroxy group again, glycosidating the resulting compound or the abovementioned 2-azido-1,3-dihydroxy compound with the 0-trifluoro- or 0-trichloro-acetimade or the 1-halogen derivative of a 2,3,4,6-0-tetraacyl-D-glucose, splitting off the acyl groups of these and the protective group in the 3-position, converting the azido group into an amino group and acylating the amino compound with a fatty acid R1 --OH. The process gives the compounds of the therapeutically more active D series in a high yield in relatively few stages without resolving diastereomers.
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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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- Synthesis of Sphingosines, 4. - Synthesis of erythro-Sphingosines via Their Azido Derivatives
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The 2,4-O-protected D-threoses 3a and 3b were obtained from D-galactose and D-xylose, respectively, in two-step procedures.Wittig reaction in the presence of an excess of lithium bromide afforded the trans-enetriols 4aA, 4aB, and 4bA.Triflate activation of the unprotected 2-hydroxy group, azide group introduction, and cleavage of the O-protective groups yielded the azidosphingosines 6A,B which provide after azide group reduction the D-erythro-sphingosines 7A,B.For the glycosphingolipid synthesis through azidosphingosine glycosylation, compound 6A was transformed by 1-O tritylation, 3-O protection, and subsequent 1-O detritylation into the 3-O-protected azidosphingosines 11α-11γ.
- Zimmermann, Peter,Schmidt, Richard R.
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p. 663 - 668
(2007/10/02)
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- A NOVEL ROUTE TO D-erythro-SPHINGOSINE AND RELATED COMPOUNDS FROM MONO-O-ISOPROPYLIDENE-D-XYLOSE OR -D-GALACTOSE
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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
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p. 101 - 112
(2007/10/02)
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- SYNTHESIS OF D-ERYTHRO-SPHINGOSINES
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2,4-Di-O-protected D-threose, readily available from D-galactose, is a versatile intermediate for D-erythro-sphingosine syntheses via trans-selective Wittig reaction, azide introduction at the unprotected hydroxylic group, and subsequent azide reduction.
- Schmidt, Richard R.,Zimmermann, Peter
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p. 481 - 484
(2007/10/02)
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