Synthesis and application of chiral stationary phase bound with novel carbohydrate polymers for optical resolution system

新型碳水化合物聚合物结合手性固定相的合成及其在光学拆分系统中的应用

• 批准号: 11555244
• 负责人: KAKUCHI Toyoji
• 金额: $ 8.58万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11555244/
• 关键词: 1,6-Anhydro sugar; Ring-opening polymerization; Optical resolution; (1→6)-α-D-Glucopyranan; (1→6)-α-D-Mannopyranan; Phenylcarbamate derivatives; Chiral stationary phase; Stereoregular polysacharide; 1.6-無水糖; (1→6)-α-D-グルコピラナン; (1→6)-α-D-マンノピラナン

The research aimed to synthesize and apply novel carbohydrate polymers for optical resolution system, and the author reported that 1) the ring-opening polymerization of 1,6-anhydro sugar and 2) the optical resolution of (l→6)-α-D-hexopyranan phenylcarbamate derivatives as chiral stationary phase in HPLC.1) For the convenient synthesis of (1→6)-α-D-glucopyranan, the ring-opening polymerization of 2,3,4-tri-O-allyl-β-D-glucopyranose (1) have been carried out using BF_3・OEt_2. For the condition of [BF_3・OEt_2]/[1] = 0.05 at 0℃ for 140 h, the yield and M_w of the obtained polymer were 84.0 % and 44,300 (DP_n = 157), respectively. The polymer structure was (1→6)-α-linked 2,3,4-tri-O-allyl-D-glucopyranose, i.e., (1→6)-2,3,4-tri-O-allyl-D-glucopyranan (2), The resulting polymer 2 was isomerized using triphenylphosphinechlororhodium as a catalyst in toluene/ethanol/water to yield (1→6)-2,3,4-tri-O-propenyl-α-D-glucopyranan (3). Then the deprotection of the propenyl ether linkage in the obtaine … More d polymer 3 was performed using HCl in acetone to give (1→6)-α-D-glucopyranan.2) Synthetic polysaccharides, (1→6)-α-D-glucopyranan (3a) and (1→6)-α-D-mannopyranan (3b), were prepared by the cationic ring-opening polymerization of 1,6-anhydro-2,3,4-tri-O-aIlyl-β-D-glucopyranose (1a) and 1,6-anhydro-2,3,4-tri-O-allyl-β-D-mannopyranose (1b), followed by the cleavage of the allyl ether linkage of 2,3,4-tri-O-allyl-(1→6)-α-D-glucopyranan (2a) and 2,3,4-tri-O-allyl-(1→6)-α-D-mannopyranan (2b), respectively. 2,3,4-Tris-O-(3,5-dimethylphenylcarbamoyl)- and 2,3,4-tris-O-(3,5-dichlorophenylcarbamoyl)-(1→6)-α-D-glucopyranan (CSP-1 and CSP-2, respectively) and 2,3,4-tris-O-(3,5-dichlorophenylcarbamoyl)-(1→6)-α-D- mannopyranan (CSP-3 and CSP-4, respectively) were prepared by the reaction of 3 with the corresponding 3,5-disubstituted phenylisocyanates, and the chiral recognition abilities of CSP-1〜4 as chiral stationary phases (CSPs) in high-performance liquid chromatography (HPLC) were evaluated. The racemic compounds such as /trans-cyclopropanedicarboxylic acid dianilide (9), 1,2,2,2-tetraphenylethanol (10), flavanone (11), Troger's base (12), benzoin (13), and cobalt(III) tris(acetylacetonate) (14) were efficiently resolved using CSP-1〜4. For comparison among CSPs, the chirai recognition property of the (1→6)-α-D-glucopyranan CSPs was different from that of the (1→6)-α-D-maannopyranan CSPs, and CSP-4 exhibited the highest chiral recognition ability among the CSPs. The resolution factors of 12 and 14 were 0.42 and 0.56 for CSP-1, 0.32 and 2.16 for CSP-2, 1.80 and 0.84 for CSP-3, and 2.31 and 8.26 for CSP-4, respectively. Less

本研究旨在合成和应用新型糖类聚合物作为光学拆分体系，报道了1）1，6-脱水糖的开环聚合和2）（1 →6）-α-D-己吡喃苯氨基甲酸酯衍生物作为HPLC手性固定相的光学拆分。1）为了方便合成（1→6）-α-D-吡喃葡萄糖，2，3，用BF_3·OEt_2合成了4-三-O-烯丙基-β-D-吡喃葡萄糖（1）。在[BF_3·OEt_2]/[1] = 0.05、0℃反应140 h的条件下，聚合物的产率为84.0%，分子量为44，300（DP_n = 157）。聚合物结构为（1→6）-α-连接的2，3，4-三-O-烯丙基-D-吡喃葡萄糖，即，（1→6）-2，3，4-三-O-烯丙基-D-吡喃葡萄糖（2），在甲苯/乙醇/水体系中，用三苯基膦氯化铑作催化剂，将所得聚合物2异构化，得到（1→6）-2，3，4-三-O-丙烯基-α-D-吡喃葡萄糖（3）。然后将所得产物中的丙烯基醚键脱保护， ...更多信息 2）以1，6-脱水-2，3，4-三-O-烯丙基-β-D-吡喃葡萄糖（1a）和1，6-脱水-2，3，4-三-O-烯丙基-β-D-吡喃葡萄糖（3b）为原料，通过阳离子开环聚合制备了（1 → 6）-α-D-吡喃葡萄糖（3a）和（1→6）-α-D-吡喃甘露糖（3b）。2，3，4-三-O-烯丙基-（1→6）-α-D-吡喃葡萄糖（2a）和2，3，4-三-O-烯丙基-（1 → 6）-α-D-吡喃甘露糖（2b）的烯丙基醚键分别断裂。2，3，4-三-O-（3，5-二甲基苯基氨基甲酰基）-和2，3，4-三-O-（3，5-二氯苯氨基甲酰基）-（1→6）-α-D-吡喃葡萄糖（分别为CSP-1和CSP-2）和2，3，4-三-O-（3，5-二氯苯氨甲酰基）-（1→6）-α-D-甘露吡喃（分别为CSP-3和CSP-4）通过3与相应的3，5-二取代的苯基异氰酸酯反应制备，考察了CSP-1和CSP-4作为高效液相色谱手性固定相的手性识别能力。外消旋化合物如反式-环丙烷二羧酸二苯胺（9）、1，2，2，2-四苯基乙醇（10）、黄烷酮（11）、Troger碱（12）、安息香（13）和三乙酰丙酮钴（III）（14）用CSP-1104有效地拆分。通过比较，（1 → 6）-α-D-吡喃葡萄糖和（1→6）-α-D-吡喃甘露糖的手性识别能力不同，其中CSP-4的手性识别能力最强。CSP-1的12和14的分辨率因子分别为0.42和0.56，CSP-2为0.32和2.16，CSP-3为1.80和0.84，CSP-4为2.31和8.26。少

项目成果

T.Kakuchi: "PRECISION SYNTHESIS OF (1→6)-α-D-GLUCOPYRANAN BY CATIONIC RING-OPENING POLYMERIZATION OF 1,6-ANHYDRO-β-D-GLUCOPYRANOSE"Macromolecular Symposia. (in press). (2002)

T.Kakuchi：“通过 1,6-酐-β-D-吡喃葡萄糖的阳离子开环聚合精确合成 (1→6)-α-D-吡喃葡萄糖”（Macromoletical Symposia）（2002 年出版）。

A. Kusuno, M. Mori, T. Satoh, M. Miura, H. Kaga, T. Kakuchi: "Enantioseparation Property of(1→6)-α-D-Glucopyranan and (1→6)-α-D-Mannopyranan Tris(phenylcarbarnate)s as Chiral Stationary Phases in HPLC"Chirality. (in press). (2002)

A. Kusuno、M. Mori、T. Satoh、M. Miura、H. Kaga、T. Kakuchi：“(1→6)-α-D-吡喃葡萄糖和(1→6)-α-D-的对映分离性质甘露吡喃三(苯基氨基甲酸酯)作为 HPLC 中的手性固定相“手性。（印刷中）。（2002 年）

T.Kakuchi: "Ring-opening and ring-forming polymerization of 1,2:5,6:9, 10-triepoxydecane leading to highly regioselective polymer consisting of octahydrobifuranyl unit"Macromolecules. 33. 246-247 (2000)

T.Kakuchi：“1,2:5,6:9, 10-三环氧癸烷的开环和成环聚合产生由八氢联呋喃基单元组成的高度区域选择性聚合物”大分子。

覚知豊次: "超臨界流体を反応溶媒とした多糖誘導体の合成"Cellulose Commun.. 8. 66-70 (2001)

角地丰二：“使用超临界流体作为反应溶剂的多糖衍生物的合成”Cellulose Commun.. 8. 66-70 (2001)

K. Yokota, H. Hashimoto, T. Satoh, S. Umeda, T. Kakuchi: "Syntheses of novel carbohydrate polymers via regio- and stereoselective cyclopolymerization of 1,2:5,6-dianhydrohexitols"Recent Researche Developments in Polymer Science. 5. 63-77 (2000)

K. Yokota、H. Hashimoto、T. Satoh、S. Umeda、T. Kakuchi：“通过 1,2:5,6-二脱水己糖醇的区域和立体选择性环聚合合成新型碳水化合物聚合物”聚合物科学的最新研究进展。