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Convergent Synthesis of Sialyl LewisX- O-Core-1 Threonine.

ABSTRACT: Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl LewisX (sLeX) linked to a Core-1- O-hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using ?-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.

SUBMITTER: Sardar MYR

PROVIDER: S-EPMC7648531 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Convergent Synthesis of Sialyl Lewis<sup>X</sup>- O-Core-1 Threonine.

Sardar Mohammed Y R MYR Mandhapati Appi Reddy AR Park Simon S Wever Walter J WJ Cummings Richard D RD Chaikof Elliot L EL

The Journal of organic chemistry 20180423 9

Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl Lewis<sup>X</sup> ...[more]

PMID: 29638128

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Synthesis of LewisX-O-Core-1 threonine: A building block for O-linked LewisX glycopeptides.

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Cloning and characterization of a viral ?2-3-sialyltransferase (vST3Gal-I) for the synthesis of sialyl Lewisx.

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Chemoenzymatic synthesis of functional sialyl Lewis(x) mimetics with a heteroaromatic core.

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Total synthesis of trifluorobutyryl-modified, globally protected sialyl Lewis x by a convergent [2+2] approach.

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Regioselective One-Pot Multienzyme (OPME) Chemoenzymatic Strategies for Systematic Synthesis of Sialyl Core 2 Glycans.

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Short Convergent Synthesis of the Mycolactone Core Through Lithiation-Borylation Homologations.

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Enantioselective, Convergent Synthesis of the Ineleganolide Core by a Tandem Annulation Cascade.

Project description:An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis-cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation-Cope rearrangement cascade under unusually mild conditions. Computational evaluation of ground state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures. This work represents the first successful synthesis of the core structure of any member of the polycyclic norcembranoid diterpene family of natural products. Advanced synthetic manipulations generated a series of natural product-like compounds that were shown to possess selective secretory antagonism of either interleukin-5 or interleukin-17. This bioactivity stands in contrast to the known antileukemic activity of ineleganolide and suggests the norcembranoid natural product core may serve as a useful scaffold for the development of diverse therapeutics.

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Correction: Enantioselective, convergent synthesis of the ineleganolide core by a tandem annulation cascade.

Project description:[This corrects the article DOI: 10.1039/C6SC03347D.].

| S-EPMC6349058 | biostudies-literature

Synthesis of an Fmoc-threonine bearing core-2 glycan: a building block for PSGL-1 via Fmoc-assisted solid-phase peptide synthesis.

Project description:Selectins (L, E, and P) are vascular endothelial molecules that play an important role in the recruitment of leukocytes to inflamed tissue. In this regard, P-Selectin glycoprotein-1 (PSGL-1) has been identified as a ligand for P-Selectin. PSGL-1 binds to P-Selectin through the interaction of core-2 O-glycan expressing sialyl Lewis(x) oligosaccharide and the three tyrosine sulfate residues. Herein, we report the synthesis of threonine-linked core-2 O-glycan as an amino acid building block for the synthesis of PSGL-1. This building block was further incorporated in the Fmoc-assisted solid-phase peptide synthesis to provide a portion of the PSGL-1 glycopeptide.

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