A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF2-linked ganglioside GM4 analog

Mikiko Sodeoka; Go Hirai; Toru Watanabe; Taeko Miyagi

doi:10.1351/PAC-CON-08-09-14

A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF₂-linked ganglioside GM4 analog

Mikiko Sodeoka, Go Hirai, Toru Watanabe, Taeko Miyagi

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

Abstract

Sialidase-resistant ganglioside analogs having similar biological activities to natural gangliosides are expected to be important probes for clarifying the biological functions of gangliosides. Focusing on difluoromethylene-linked (CF₂-linked) and methylene-linked (CH ₂-linked) α(2,3)sialylgalactose as a core structure of sialidase-resistant ganglioside mimics, we have developed novel, stereocontrolled, and efficient methodologies to synthesize C-sialosides based on Ireland - Claisen rearrangement. These methods were employed to synthesize CF₂-linked GM4. The CF₂-linked GM4 inhibited human sialidases NEU2 and NEU4 with IC₅₀ values of 754 and 930 μM, respectively, and strongly inhibited human lymphocyte proliferation in the same concentration range as natural GM4.

Original language	English
Pages (from-to)	205-215
Number of pages	11
Journal	Pure and Applied Chemistry
Volume	81
Issue number	2
DOIs	https://doi.org/10.1351/PAC-CON-08-09-14
Publication status	Published - Mar 9 2009
Externally published	Yes

All Science Journal Classification (ASJC) codes

Chemistry(all)
Chemical Engineering(all)

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10.1351/PAC-CON-08-09-14

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abstract = "Sialidase-resistant ganglioside analogs having similar biological activities to natural gangliosides are expected to be important probes for clarifying the biological functions of gangliosides. Focusing on difluoromethylene-linked (CF2-linked) and methylene-linked (CH 2-linked) α(2,3)sialylgalactose as a core structure of sialidase-resistant ganglioside mimics, we have developed novel, stereocontrolled, and efficient methodologies to synthesize C-sialosides based on Ireland - Claisen rearrangement. These methods were employed to synthesize CF2-linked GM4. The CF2-linked GM4 inhibited human sialidases NEU2 and NEU4 with IC50 values of 754 and 930 μM, respectively, and strongly inhibited human lymphocyte proliferation in the same concentration range as natural GM4.",

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AU - Sodeoka, Mikiko

AU - Hirai, Go

AU - Watanabe, Toru

AU - Miyagi, Taeko

PY - 2009/3/9

Y1 - 2009/3/9

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AB - Sialidase-resistant ganglioside analogs having similar biological activities to natural gangliosides are expected to be important probes for clarifying the biological functions of gangliosides. Focusing on difluoromethylene-linked (CF2-linked) and methylene-linked (CH 2-linked) α(2,3)sialylgalactose as a core structure of sialidase-resistant ganglioside mimics, we have developed novel, stereocontrolled, and efficient methodologies to synthesize C-sialosides based on Ireland - Claisen rearrangement. These methods were employed to synthesize CF2-linked GM4. The CF2-linked GM4 inhibited human sialidases NEU2 and NEU4 with IC50 values of 754 and 930 μM, respectively, and strongly inhibited human lymphocyte proliferation in the same concentration range as natural GM4.

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A strategy for constructing C-sialosides based on Ireland-Claisen rearrangement and its application for synthesis of CF₂-linked ganglioside GM4 analog

Abstract

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