Dataset Information

Stereoselective Synthesis of 5-epi-?-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids.

ABSTRACT: With a view to the eventual synthesis of glycosyl donors for the stereocontrolled synthesis of pseudaminic acid glycosides, the stereocontrolled synthesis of a d-glycero-d-gulo sialic acid adamantanylthioglycoside carrying an axial azide at the 5-position is described. The synthesis employs levulinic acid as nucleophile in the oxidative deamination of an N-acetylneuraminic acid thioglycoside leading to the formation of a 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (KDN) derivative selectively protected as 5-O-levulinate. Replacement of the levulinate by triflate enables introduction of the axial azide and hence formation of the glycosyl donor. A shorter synthesis uses trifluoromethanesulfonate as nucleophile in the oxidative deamination step when the 5-O-triflyl KDN derivative is obtained directly. Glycosylation reactions conducted with the 5-azido-d-glycero-d-gulo-configured sialyl adamantanylthioglycoside at -78 °C are selective for the formation of the equatorial glycosides, suggesting that the synthesis of equatorial pseudaminic acid glycosides will be possible as suitable donors become available. A comparable N-acetylneuraminic acid adamantanylthioglycoside carrying an equatorial azide at the 5-position was also found to be selective for equatorial glycoside formation under the same conditions, suggesting that reinvestigation of other azide-protected NeuAc donors is merited. Glycosylation stereoselectivity in the d-glycero-d-gulo series is discussed in terms of the side-chain conformation of the donor.

SUBMITTER: Dhakal B

PROVIDER: S-EPMC5148678 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Publications

Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids.

Dhakal Bibek B Buda Szymon S Crich David D

The Journal of organic chemistry 20161110 22

With a view to the eventual synthesis of glycosyl donors for the stereocontrolled synthesis of pseudaminic acid glycosides, the stereocontrolled synthesis of a d-glycero-d-gulo sialic acid adamantanylthioglycoside carrying an axial azide at the 5-position is described. The synthesis employs levulinic acid as nucleophile in the oxidative deamination of an N-acetylneuraminic acid thioglycoside leading to the formation of a 3-deoxy-d-glycero-d-galacto-2-nonulosonic acid (KDN) derivative selectively ...[more]

PMID: 27806203

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Project description:Mahuang-Xingren (MX, Ephedra sinica Stapf-Prunus armeniaca L.) is a classic herb pair used in traditional Chinese medicine. This combined preparation reduces the toxicity of Xingren through the stereoselective metabolism of its main active ingredient amygdalin. However, whether stereoselectivity is important in the pharmacokinetic properties of amygdalin either in the traditional decoction or in the dispensing granules is unclear. Amygdalin is hydrolyzed to its metabolite, prunasin, which produces hydrogen cyanide by degradation of the cyano group. A comprehensive study of the metabolic pathway of amygdalin is essential to better understand the detoxification process. In this article, the potential detoxification pathway of MX is further discussed with regard to herb interactions. In this study, the pharmacokinetic parameters and metabolism of amygdalin and prunasin were investigated by comparing the traditional decoction and the dispensing granule preparations. In addition, several potential metabolites were characterized in an incubation system with rat liver microsomes or gut microbial enzymes. The combination of Xingren with Mahuang reduces exposure to D-amygdalin in vivo and contributes to its detoxification, a process that can be further facilitated in the traditional decoction. From the in vitro co-incubation model, 15 metabolites were identified and classified into cyanogenesis and non-cyanogenesis metabolic pathways, and of these, 10 metabolites were described for the first time. The level of detoxified metabolites in the MX traditional decoction was higher than that in the dispensing granules. The metabolism of amygdalin by the gut microbial enzymes occurred more rapidly than that by the rat liver microsomes. These results indicated that combined boiling both herbs during the preparation of the traditional decoction may induce several chemical changes that will influence drug metabolism in vivo. The gut microbiota may play a critical role in amygdalin metabolism. In conclusion, detoxification of MX may result 1) during the preparation of the decoction, in the boiling phase, and 2) from the metabolic pathways activated in vivo. Stereoselective pharmacokinetics and deamination metabolism have been proposed as the detoxification pathway underlying the compatibility of MX. Metabolic detoxification of amygdalin was quite different between the two combinations, which indicates that the MX decoctions should not be completely replaced by their dispensing granules.

Dataset Information

Stereoselective Synthesis of 5-epi-?-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids.

Publications

Stereoselective Synthesis of 5-epi-α-Sialosides Related to the Pseudaminic Acid Glycosides. Reassessment of the Stereoselectivity of the 5-Azido-5-deacetamidosialyl Thioglycosides and Use of Triflate as Nucleophile in the Zbiral Deamination of Sialic Acids.

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