Precise Chemical Synthesis of Physiologically Active Branched Polysaccharides

生理活性支链多糖的精密化学合成

• 批准号: 04650825
• 负责人: MASAHIKO Okada
• 金额: $ 1.22万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04650825/
• 关键词: Synthetic Polysaccharide; Branched Glycochain; Anhydro Sugar; Glucose; Cellulose; Stereoregulation; Ring-Opening Polymerization; Physiologically Active Polysaccharide

The objective of this study is to synthesize well-defined branched(1-3)-beta-D-glucans having beta-D-glucoss branches at their 6-positions via ring-opening polymerization of 1,3-anhydro sugar derivatives. Synthesis of the target polysaccharides was undertaken by two different approaches : 1)Polymerization of 1,3-anhydro-beta-D-glucose derivative (1), followed by selective deprotection of the p-methoxybenzyl group of the resulting polymer, subsequent stereospecific glycosidation at the 6-position, and finally complete deprotection of the product, and 2) polymerization of 1,3-anhydro-beta-D-glucose derivative (2) bearing a beta-D-glucose moiety in its 6-position, followed by deprotection of the resulting polymer.The synthesis of 1 was attempted via a 9 steps reaction sequence starting from cellulose. However, the methoxybenzyl group was removed during the chlorination of the diacetate (3) by hydrogen chloride. Therefore it is necessary to look for a more appropriate protecting group as well as milder reaction conditions. The synthesis of 2 was also undertaken with cellulose as a starting material through an 11 step reaction sequence. In the final intermolecular bicyclization step, the dehydrochlorination of the precursor chloride (4) predominantly occurred to yield a glucal derivative as the major product. The monomer 2 was cbtained in a yield of 14%. Therefor, the reaction conditions must be optimized to improve the yield of the desired product 2.Polymerization of 1,3-anhydro-2,4,6-tri-O-benzyl-beta-D-glucopyranose was investigated in order to clarify the factors influencing the stereospecific polymerization of 1,3-anhydro sugar derivatives by modified organoaluminum catalysts.

本研究的目的是通过1，3-脱水糖衍生物的开环聚合来合成在其6位具有β-D-葡萄糖支链的明确的支链（1-3）-β-D-葡聚糖。目标多糖的合成通过两种不同的方法进行：1）1，3-脱水-β-D-葡萄糖衍生物（1）的聚合，随后对所得聚合物的对甲氧基苄基进行选择性脱保护，随后在6-位进行立体特异性糖苷化，最后产物完全脱保护，和2）1，3-脱水-β-D-葡萄糖衍生物（2）在其6-位带有β-D-葡萄糖部分，然后将所得聚合物脱保护。然而，在用氯化氢氯化二乙酸酯（3）的过程中，甲氧基苄基被除去。因此，需要寻找更合适的保护基以及更温和的反应条件。2的合成也是以纤维素为起始原料通过11步反应顺序进行的。在最后的分子间双环化步骤中，前体氯化物（4）的脱氯化氢主要发生以产生作为主要产物的葡糖醛衍生物。以14%的产率得到单体2。2.研究了1，3-脱水糖衍生物在改性有机铝催化下的立体定向聚合反应，考察了影响聚合反应的因素。

项目成果

M.Okada: "Chemical Synthesis of 4-Deoxy-(1->6)-alpha-D-xylo-Hexopyranan and 3,4-Dideoxy-(1->6)-alpha-D-erythro-Hexopyranan" Carbohydrate Research. 226. 345-352 (1992)

M.Okada：“4-脱氧-(1->6)-α-D-木基-己吡喃和3,4-二脱氧-(1->6)-α-D-赤式-己吡喃的化学合成”碳水化合物研究

M.Okada: "Chemical Synthesis of 4ーDeoxyー(1→6)ーαーDーxyloーHexoーpyranan and 3,4ーDideoxyー(1→6)ーαーDーerythroーHexopyranan" Carbohydrate Research. 226. 345-352 (1992)

M.Okada：“4－脱氧－(1→6)－α－D－xylo－Hexo－pyranan和3,4－Dideoxy－(1→6)－α－D－erythro－Hexopyranan的化学合成”碳水化合物研究. 226. 345-352 (1992)

K.Kobayashi: "Steric Control in RingーOpening Polymerization of 1,6ーAnhydro Galactose Derivatives by Neighboring Group Participation" Polymer Journal. 25. 49-57 (1993)

K.Kobayashi：“通过邻近基团参与进行 1,6-脱水半乳糖衍生物的开环聚合中的空间控制”《聚合物杂志》25. 49-57 (1993)。

M.Okada: "Chemical Synthesis of Polysaccharides XI.Ring-Opening Polymerization of 1,6-Anhydro-2-O-(p-Substituted Benzoyl)Deoxysugar Derivatives" Polymer Journal. 24. 1137-1145 (1992)

M.Okada：“多糖的化学合成XI.1,6-脱水-2-O-（对位取代的苯甲酰基）脱氧糖衍生物的开环聚合”聚合物杂志。

K.Kobayashi: "Steric Control in Ring-Opening Polymerization of 1,6-Anhydro Galactose Derivatives by Neighboring Group Participation" Polymer Journal. 25. 49-57 (1993)

K.Kobayashi：“通过邻近基团参与进行 1,6-脱水半乳糖衍生物开环聚合的空间控制”聚合物杂志。