1998 Fiscal Year Final Research Report Summary
Synthesis of Glycoconjugate Derived Glycans as Molecular Probes
| Project/Area Number |
08457590
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | RIKEN (The Institute of Physical and Chemical Research) |
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Principal Investigator |
ITO Yukishige REKEN, Synthetic Cellular Chemistry Laboratory, Chief Scientist, 細胞制御化学研究室, 主任研究員 (80168385)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Glycoprotein / Glycoconjugate / Glycan Chain / b-Mannosylation / p-Methoxybenzyl / Solid Phase Synthesis / Glycosylation / Stereoselectivity |
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| Research Abstract |
The major target in this research has been the synthesis pf glycoprotein derived glycans.
Among variety of O-glycoside linkage patterns found in naturally occurring oligosaccahrides, β-glycoside of mannose is the most challenging from synthetic point of view. Its biological significance is obvious because it exists as the core structure of all types of asparagine linked glycoproteins. We have developed paramethoxybenzyl assisted intramolecular aglycon delivery (IAD) to solve this problem. After extensive optimization of several factors, it is now possible to synthesize β-mannoside containing di- (βMan1→4GlcNAc) or trisaccharide (βman1→4βGlcNAcl→4GlcNAc) in more than 80% yield. We have also assigned the stereochemistry of the mixed acetal which is the tethered intermediate in IAD. In connection with ongoing project on polymer support synthesis of oligosaccharides, following results were obtained.
1) Intramolecular aglycon delivery was successfully performed using polymer supported mannose donor. This system specifically releases the desired product and greatly simplifies the isolation process.
2) A new protecting group, dichlorophthaloyl group was developed which is potentially useful for solid phase synthesis of polylactosamine type glycan chains.
3) Orthogonal glycosylation strategy which was previously developed in this laboratory was extended to polymer support synthesis.
4) Sialic acid donor supported on polymer was synthesized and used for stereoselective glycosylation.
5) Stereoselectivity of polyme supported glycosylation reaction was investigated and discovered to have similar solvent effect as solution phase reactions.
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