Azidosphingosine Glycosylation in Glycosphingolipid Synthesis

Zimmermann, Peter; Sommer, René; Bär, Thomas; Schmidt, Richard R.

doi:10.1080/07328308808058935

Cited by 117 publications

(24 citation statements)

References 14 publications

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“…The β configuration of the newly introduced glycosidic linkage was confirmed from the 1 H NMR spectrum which showed the H-1′ (galactose unit) as a doublet at δ 4.52 ppm (J 1′,2′ =8.0 Hz). The NMR data are consistent with those reported in the literature [25,26].…”

Section: Chemical Synthesissupporting

confidence: 93%

Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies

et al. 2007

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3-O-Sulfogalactosylceramides (sulfatides) accumulate in the genetic disease metachromatic leukodystrophy which is due to a defect in the catabolic enzyme, arylsulfatase A. Clinical diagnosis is usually confirmed by in vitro enzymatic deficiency of arylsulfatase A activity. The diagnosis may be complicated because of arylsulfatase A pseudo-deficiencies and another cause of MLD, sphingolipid activator B deficiency. As large quantities of sulfatides can be found in the urine in this disease, sulfatiduria appears as an extremely useful test. As recently enzyme replacement is underway, the quantitative determination, using an internal standard, appears particularly useful as a follow-up. Thus a non-physiological sulfatide was synthesized for this purpose, i.e. 3-O-sulfo-beta-D-C17 galactosylceramide (3-O-Sulfo-D: -Galactosyl-beta1'-->1-N-Heptadecanoyl-D-erythro-Sphingosine). It has been prepared through condensation of an azidosphingosine derivative with a protected D-galactopyranosyltrichloroacetimidate. Reduction of the azide was followed by acylation of a C-17 fatty acid. The key step was achieved by selective sulfation of the desired hydroxyl group on the sugar residue of the galactosylceramide using the stannylene methodology to give a 3'-sulfated beta-galactosyl C-17 ceramide.

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Section: Chemical Synthesissupporting

confidence: 93%

Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies

et al. 2007

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“…The glycosylation involved an acetoxonium intermediate 17 [9] which was formed via the C2 neighboring group participation (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…The residue was purified by column chromatography on silica gel (petroleum ether:ethyl acetate, 12:1) to give 7 (1. (E )-1-(tert-Butyldiphenylsilyloxymethyl)-4-(4-methoxy-benzyloxy)-2-butenenitrile (9). To a solution of ketone 7 (1.17 g, 2.53 mmol) in methanol (35 mL) was added triethyl amine (0.49 mL, 3.55 mmol) and acetone cyanohydrin (1.7 mL, 18 mmol).…”

Section: Experimental General Proceduresmentioning

confidence: 99%

A Facile and Convergent Synthesis of Sarmentosin

Bai

2003

Synthetic Comm.

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“…Several groups have used pivaloyl esters to suppress acyl transfer (15). Most of these reports discuss the use of pivaloyl in terms of suppressing orthoester formation and do not discuss acyl transfer (16). Similarly, the mesitoyl (2,4,6-trimethylbenzoyl) group has also been used to suppress orthoester formation (17).…”

Section: Introductionmentioning

confidence: 98%

Is acyl migration to the aglycon avoidable in 2-acyl assisted glycosylation reactions?

Bérces¹,

Whitfield²,

Nukada³

et al. 2004

Can. J. Chem.

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This report unequivocally separates orthoester formation from acyl transfer for the first time and indicates possible routes to eliminate 2-O-acyl transfer during glycosylation reactions. Experimental evidence is shown that acyl transfer from 2-O-acyl-3,4,6-tri-O-benzyl-D-galactopyranose-derived glycosyl donors decreases in the order formyl > acetyl > pivaloyl. The 2-O-benzoyl derivatives are more variable, in some cases transferring easily, and in others not at all. Density functional theory (DFT) calculations of the structure and energetics of dioxolenium ion and related intermediates suggest that a proton transfer pathway from the nucleophile to O-2 provides an explanation for the observed trends. These DFT calculations of the proton transfer pathway support a mechanism in which a relay molecule is involved. Further DFT calculations used a constraint based on linear combinations of six bond lengths to establish the sequence of bond breaking and bond forming. The calculated anomeric carbon to former carbonyl oxygen bond that breaks during acyl transfer is the longest in the formyl case and shortest in those that exhibit little or no acyl transfer. Rotation about the aromatic to carbonyl Ph-C(=O) bond is different from the alkyl series. Analysis of this proposed TS led to the postulate that 2,6-substitution may hinder rotation even more. Thus, the 2,6-dimethylbenzoyl analogue was synthesized and it does not transfer directly or by rearrangement of its readily formed orthoester. DFT calculations suggested that 2,6-dimethoxybenzoyl should also not transfer easily. Experimentally, this proved to be the case and this new 2-O-acyl protecting group cleaves at 50°C with a 1 mol/L solution of LiOH in methanol. Thus, a calculated transition state has led to a prototype of a protecting group that solves a major problem in oligosaccharide synthesis. Résumé: Dans ce travail, on sépare sans équivoque et pour la première fois la formation d'orthoester des transferts d'acyles et on suggère des voies possibles pour éliminer le transfert de 2-O-acyle lors des réactions de glycosylation. On présente des données expérimentales montrant que le transfert d'acyle de donneurs glycosyles dérivés du 2-O-acyl-3,4,6-tri-O-benzyl-D-galactopyranose diminue dans l'ordre formyle > acétyle > pivaloyle. Les dérivés 2-O-benzoyles sont plus variables; dans certains cas, le transfert se fait facilement alors que dans d'autres il ne se fait pas du tout.Des calculs basés sur la théorie de la densité fonctionnelle (THF) de la structure et des énergies de l'ion dioxolénium et d'intermédiaires apparentés suggèrent qu'un transfert de proton du nucléophile vers O-2 s'avère la meilleure explication pour les tendances observées. Ces calculs de THF de la voie de transfert de proton appuient un mécanisme dans lequel une molécule relais serait impliquée. Des calculs supplémentaires de THF ont été réalisés en appliquant une contrainte basée sur des combinaisons linéaires de six longueurs de liaisons pour déterminer la séquence de bris et de formation de la lia...

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Azidosphingosine Glycosylation in Glycosphingolipid Synthesis

Cited by 117 publications

References 14 publications

Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies

Synthetic sulfogalactosylceramide (sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies

A Facile and Convergent Synthesis of Sarmentosin

Is acyl migration to the aglycon avoidable in 2-acyl assisted glycosylation reactions?

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