1990 Fiscal Year Final Research Report Summary
Synthesis of the Hexasaccharides Containing Nitrogen Atoms Starting from Lactose
| Project/Area Number |
01571159
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Chemical pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
CHIBA Taku Nagoya City University Instructor Faculty of Pharmaceutical Sciences, 薬学部, 講師 (10094385)
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| Project Period (FY) |
1989 – 1990
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| Keywords | Synthesis / Oligosaccharides in the human milk / Lacto-N-hexaose / Para-lacto-N-neohexaose / Oxazoline method / N-Acetyllactosamine / Lacto-N-biose I / Trimethylsilyl triflate |
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| Research Abstract |
It is of common knowledge to be more than sixty oligosaccharides in the human milk. In the latter half of 1960, Hakomori, et al. Reported that there were some ceramides of the human milk oligosaccharides (ex. lacto-N-neotetraose and difucosylーparaーlactoーNーneohexaose, etc.) in the glycolipids of the cell surface of some cancers. As a representative of investigation has studied the chemical modification and inversion of lactose, and syntheses of the human milk oligosaccharides and their analogues since 1971, now he has aimed to synthesize the hexasaccharides containing nitrogen atoms, lacto-N-hexaose (1) which was contained in small amount in the human milk and paraーlacto-Nneohexaose (2) which was a core hexasaccharide in the glycolipids of the cell surface of some cancers. About the synthesis of (1), starting from benzy1 betalactoside (3), selective allylation of C-3' position, benzylidenation, benzylation, followed by selective cleavage of benzylidene acetal gave a main product (4) with the free C-6' position. Coupling (4) with the oxazoline derivative of N-acetyllactosamine gave the tetrasaccharide derivatine (5) in 73.1% yield. After deallylation of (5), coupling with the oxazoline derivative of lactoN-biose I gave the hexaseaccharide derivative (6) in 36.2% yield. Deprotection of (6) gave (1) in 78.9% yield. About the synthesis of (2), starting from (3), a lactose derivative (7) with the free C-3' and 4' positions was obtained by chemical modification. A lactosamine derivative (8) with N-phthaloyl and allyl groups in C-2 and 3' positions, respectively, and that (9) with Nーphthaloyl group were prepared via lactal derivative by chemical modification. Coupling (7) with (8) in the presence of trimethylsilyl triflate as promoter gave the tetrasaccharide derivative (10) in 49% yield. After deallylation of (10), coupling with (9) gave the hexasaccharide derivative (11) in 21% yield. Hereafter, deprotection of (11) will give (2).
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