Grant-in-Aid for General Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Kitasato University |
OGURA Haruo Kitasato Univ., Pharm. Sci., Professor, 薬学部, 教授 (90050335)
YAMASAKI Toshiko Kitasato Univ., Pharm. Sci., Assistant, 薬学部, 助手 (60230380)
KAI Toshitugu Kitasato Univ., Pharm. Sci., Assistant, 薬学部, 助手 (30224322)
FURUHATA Kimio Kitasato Univ., Pharm. Sci., Lecturer, 薬学部, 講師 (60050605)
TAKAYANAGI Hiroaki Kitasato Univ., Pharm. Sci., Ass. Professor, 薬学部, 助教授 (00050477)
TAKEDA Kazuyoshi Kitasato Univ., Pharm. Sci., Lecturer (10050684)
SIRAI Ryuiti Kitasato Univ., Pharm. Sci., Assistant (80183838)
|Project Period (FY)
1988 – 1990
Completed (Fiscal Year 1990)
|Budget Amount *help
¥5,100,000 (Direct Cost: ¥5,100,000)
Fiscal Year 1990: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1989: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
|Keywords||N-acetylneuraminic acid / KDN / glycosylation / stereochemistry / Koenigs-Knorr / グリコシド / 神経突起伸展 / N__ーーアセチルノイラミン酸 / Neu5Ac / 立体配置 / 神経細胞増生 / N-アセチルノイラミン酸 / N-アセチル-2,3-デヒドロ-2-デオキシノイラミン酸 / 1,7-ラクトン誘導体 / 3-デオキシ-D-ノヌロン酸 / X線解析 / 立体化学|
1. Synthesis of KDN
Neu5Ac was obtained from edible bird's nest, and KDN was synthesized from D-mannose and oxalacetic acid. Because the yield of thermal rearrangement of Neu5Ac nitroso derivative to KDN was very low.
2. Glycosilation of Neu5Ac
Syntheses of various kind of Neu5Ac derivatives were carried out from (Neu4, 5, 7, 8, 9-Ac_52betaCl1Me). From the chloride, sialosyl-lactose, -cholesterol, -monosaccharide, and -disaccharide nucleoside analogs were synthesized under the Koenigs-Knorr reaction conditions.
3. Glycosylation of KDN
Benzyl (methyl 3-deoxy-D-glycero-alpha-D-galacto-2-nonulopyranosid) onate and sodium 2- (5-cholestenyl-3beta-oxy) -3-deoxy-D-glycero-alpha-and-beta-D-galacto-2-nonulopyranosonate were synthesized under the Koenigs-Knorrection. Benzyl (4, 5, 7, 8, 9-penta-0-acetyl-3-deoxy-D-glycero-beta-D-galacto-2-nonulopyranosyl bromid) onate was used as a glycosyl donor.
4. Glycosylation with Williamson Reaction
Williamson reaction was applied to ferrulic acid, estradiol, umberiferon, and mitomycin derivatives with Neu5Ac chloride to yield alpha-glycosides in good yields. Mitomycin derivatives were prepared, by a similar method.
5. Confirmation of stereochemistry
(1) NMR and CD spectral method Their structure and stereochemistry were determined by means of NMR and CD spectral analyses.
(2) Hydrolysis method Hydrolysis of alpha-and beta-methyl neuraminate were proved. alpha-Anomer was hydrolyzed in 1 hr, while, beta-anomer was stable after 5 hr. Similarly, alpha- (2->6) sialosyllactose was hydrolyzed completely at 80ﾟC in 1 hour. In contrast, the beta-anomer was stable at 80^ﾟC for 5 hr.