- NOVEL SYNTHESIS INTERMEDIATES FOR OBTAINING DERIVATIVES OF SPHINGOSINES, CERAMIDES AND SPHINGOMYELINS WITH GOOD YIELDS
-
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.
- -
-
-
- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
-
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.
- -
-
-
- METHODS FOR THE SYNTHESIS OF SPHINGOMYELINS AND DIHYDROSPHINGOMYELINS
-
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.
- -
-
-
- Synthesis of α-l-rhamnosyl ceramide and evaluation of its binding with anti-rhamnose antibodies
-
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.
-
p. 5279 - 5289
(2014/12/11)
-
- The total synthesis of ganglioside GM3
-
Previous syntheses of ganglioside GM3 (NeuAcα3Galβ4Glcβ1Cer) are reviewed, and both chemoenzymatic and chemical total synthetic approaches were investigated. In a chemoenzymatic approach, (2S,3R,4E)-5'''-acetyl-α-neuraminyl-(2''' → 3'')-β-galactopyranosyl-(1'' → 4')-β-glucopyranosyl-(1' mutually implies 1)-2-azido-4-octadecene-1,3-diol (azidoGM3) was readily prepared utilizing recombinant β-Gal-(1'' → 3'/4')-GlcNAc α-(2''' → 3'')-sialyltransferase enzyme, and was evaluated as a synthetic intermediate to ganglioside GM3. The chemical total synthesis of ganglioside GM3 was performed on one of the largest scales yet reported. The highlights of this synthesis include minimizing the steps necessary to prepare the lactosyl acceptor as a useful anomeric mixture, which was present in excess for the highly regioselective and fairly stereoselective sialylation with a known neuraminyl donor to give the protected GM3 trisaccharide. The synthetic methodology maximized convergence by a subsequent glycosidic coupling of the well-characterized GM3 trisaccharide trichloroacetimidate derivative with protected ceramide. The ganglioside GM3 was nearly homogeneous as the two glycosidic couplings utilized preparative HLPC purifications, and variations in the sphingosine base and fatty acyl group were under 0.1 and 0.2%, respectively. (C) 2000 Elsevier Science Ltd.
- Duclos Jr., Richard I.
-
p. 489 - 507
(2007/10/03)
-
- A Convenient Synthesis of Galactocerebroside Using D-Glucosamine as a Chiral Source of the Ceramide Moiety
-
Galactocerebroside has been efficiently synthesized in 11 steps starting from N-benzoyl-D-glucosamine via 3-O-benzoylceramide with minimal manipulations of protecting groups.
- Murakami, Teiichi,Minamikawa, Hiroyuki,Hato, Masakatsu
-
p. 1875 - 1876
(2007/10/02)
-
- Syntheses of two pairs of enantiomeric C18-sphingosines and a palmitoyl analogue of gaucher spleen glucocerebroside
-
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
-
p. 1154 - 1165
(2007/10/02)
-
- SYNTHESES OF D-ERYTHRO-1-DEOXYDIHYDROCERAMIDE-1-SULFONIC ACID AND PHOSPHONOSPHINGOGLYCOLIPID FOUND IN MARINE ORGANISM VIA A COMMON PRECURSOR
-
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.
-
p. 2557 - 2570
(2007/10/02)
-