CN108658771B - 联萘酚聚醚链桥连手性分子钳及其制备和应用 - Google Patents
联萘酚聚醚链桥连手性分子钳及其制备和应用 Download PDFInfo
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- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
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Abstract
本发明公开了联萘酚聚醚链桥连手性分子钳及其制备和应用。所述联萘酚聚醚链桥连手性分子钳是以手性联萘酚聚醚链为隔离基、以异斯特维醇为手性臂,结构如式(I)、式(II)、式(IV)、式(V)或式(VI)所示。本发明提供了所述的联萘酚聚醚链桥连手性分子钳在识别手性分子客体中的应用,所述的手性分子客体为D/L‑氨基酸酯盐酸盐。本发明合成的分子钳对D/L‑氨基酸酯盐酸盐具有一定的手性识别性能,可用于手性识别分离对映异构体。
Description
(一)技术领域
本发明涉及一种以ent-贝叶烷二萜骨架为手性识别基团的手性分子钳化合物及其制备方法和在手性分子识别领域的应用,属于手性识别分离领域。
(二)背景技术
分子识别是生物体系的基本特征,并在生命活动中起重要作用。当一对手性对映异构体进入生命体后,两个对映异构体常常会表现出截然不同的生物活性,所以对手性物质的对映异构体进行手性识别分离是非常有意义的。手性联萘酚具有轴手性,ent-贝叶烷型二萜分子骨架具有刚性的疏水外壁、凹面的结构和固有的不对称性,利用ent-贝叶烷型二萜分子骨架结构的不对称性,研究开发新型的具有手性识别能力的超分子化合物,在功能材料、医药、生化等领域具有广阔的应用前景。
(三)发明内容
本发明目的在于提供一种新的具有手性分子识别功能的以手性联萘酚聚醚链和ent-贝叶烷骨架结构为手性源、分子中含有两个ent-贝叶烷二萜骨架的手性分子钳化合物及其制备方法,以及在手性识别分离中的应用。
为实现上述目的,本发明采用如下技术方案:
本发明提供了联萘酚聚醚链桥连手性分子钳,其以手性联萘酚聚醚链为隔离基、以异斯特维醇为手性臂,结构如式(I)、式(II)、式(IV)、式(V)或式(VI)所示:
本发明提供了一种式(I)或式(II)或式(IV)所示的联萘酚聚醚链桥连手性分子钳的制备方法,所述的制备方法包括:
将式(IX)所示化合物、无水THF、NaOH固体置于反应容器中,迅速升温至回流,加入式(XIV)或式(XV)或式(XVII)化合物的无水THF溶液,在油浴30~100℃条件下反应1~10h,之后所得反应液b经后处理,制得相应的式(I)或式(II)或式(IV)所示的联萘酚聚醚链桥连手性分子钳;
进一步,所述式(IX)所示化合物与化合物(XIV)或式(XV)或式(XVII)、NaOH的物质的量之比为1:0.1~0.5:0.5~3;所述THF的体积用量以式(IX)所示化合物的质量计为10~40mL/g。
进一步,所述反应液b的后处理方法为:反应液b冷却至室温,抽滤,取滤液减压浓缩,经硅胶柱层析(优选以石油醚/丙酮为洗脱试剂,其中石油醚:丙酮=8:1),制得式(I)、(II)或(IV)所示的分子钳化合物。
本发明提供了一种式(V)或式(VI)所示的联萘酚聚醚链桥连手性分子钳的制备方法,所述的制备方法包括:
(1)将式(IX)所示化合物、无水THF、NaOH固体置于反应容器中,迅速升温至回流,加入式(XIV)或式(XVI)化合物的无水THF溶液,在油浴30~100℃条件下反应1~10h,之后所得反应液b'经后处理,制得相应的式(I)或式(III)所示的手性分子钳;
(2)将式(I)或式(III)所示的手性分子钳溶于乙醇,加入过量NaBH4,在室温条件下反应4~8h,所得反应液c经后处理制得相应的式(V)或式(VI)所示的联萘酚聚醚链桥连手性分子钳;
进一步,步骤(1)中,所述式(IX)所示化合物与化合物(XIV)或式(XVI)、NaOH的物质的量之比为1:0.1~0.5:0.5~3;所述THF的体积用量以式(IX)所示化合物的质量计为10~40mL/g。
进一步,步骤(2)中,所述NaBH4的用量相对于式(I)或式(III)所示化合物过量,式(I)或式(III)所示化合物与NaBH4的物质的量之比为1:2~10;所述乙醇的体积用量通常以式(I)或(III)所示化合物的质量计为10~60mL/g。
进一步,所述反应液b'的后处理方法为:反应液b'冷却至室温,抽滤,取滤液减压浓缩,经硅胶柱层析(优选以石油醚/丙酮为洗脱试剂,其中石油醚:丙酮=8:1),制得式(I)或(III)所示的分子钳化合物。
进一步,所述反应液c的后处理方法为:反应结束后,向反应液中加水淬灭反应,用5wt%~20wt%HCl溶液中和,减压蒸去乙醇,CH2Cl2萃取,收集有机相,有机相依次经水洗、无水Na2SO4干燥、抽滤、滤液旋蒸除去溶剂,制得式(V)或式(VI)所示化合物。
本发明中,所述的式(IX)所示化合物、式(XIV)、式(XV)、式(XVI)、式(XVII)均为已知化合物,其制备可参考公开文献。
具体而言,所述式(IX)所示化合物推荐通过如下步骤进行制备:
(a)将式(VII)所示甜菊糖苷溶于10wt%~20wt%硫酸溶液中,在75~80℃下搅拌反应5~6h,之后冷却至室温,抽滤,滤饼用丙酮重结晶,制得式(VIII)所示化合物;所述10wt%~20wt%硫酸溶液的体积用量以式(VII)所示甜菊糖苷的质量计为30~100mL/g(优选50~70mL/g);
(b)将步骤(a)制得的式(VIII)所示化合物溶于二氯亚飒,60~75℃条件下反应1~3h,减压蒸馏除去多余的二氯亚飒,得褐色固体,褐色固体用正己烷重结晶,制得式(IX)所示化合物;
式(VII)中,Glu为葡萄糖基的缩写。
所述的式(XIV)、式(XV)、式(XVI)、式(XVII)推荐按照如下方法进行制备:
将反应物A、反应物B、碳酸钾和DMF置于反应容器中,在70~150℃条件下搅拌反应4~48h,之后反应液a经后处理,制得相应的式(XIV)或式(XV)或式(XVI)或式(XVII)所示化合物;所述反应物A选自化合物(X)或化合物(XI),所述反应物B选自化合物(XII)或(XIII),所述反应物A与反应物B、碳酸钾的物质的量之比为1:1~6:1~6;所述DMF的体积用量以反应物A的质量计为10~40mL/g;
进一步,所述反应液a后处理方法为:向反应液a中加入水,以CH2Cl2萃取,萃取液用水洗涤,无水Na2SO4干燥,抽滤,取滤液减压旋干,再经硅胶柱层析(优选以石油醚/丙酮作为洗脱试剂,其中体积比石油醚∶丙酮=2:1),制得式(XIV)、(XV)、(XVI)或(XVII)所示化合物;
本发明中,术语“反应液a”、“反应液b”、“反应液b'”、“反应液c”没有特殊的含义,标记为“a”、“b”、“b'”“c”只是用于区分不同步骤中的反应液。
本发明进一步提供了所述的联萘酚聚醚链桥连手性分子钳在识别手性分子客体中的应用,所述的手性分子客体为D/L-氨基酸酯盐酸盐。
优选的,所述的手性分子客体为D/L-苯甘氨酸甲酯盐酸盐。
本发明的实验结果表明,主体化合物(I)、(II)、(III)、(IV)、(V)和(VI)对D-和L-氨基酸酯盐酸盐均能形成超分子配合物,并且有较大的结合常数Ka。化合物(I)、(II)、(IV)、(V)、(VI)与D型和L-苯甘氨酸甲酯盐酸盐的结合常数不同,由于这种结合常数的差异可分离苯甘氨酸甲酯对映异构体。因此,本发明合成的分子钳对D/L-氨基酸酯盐酸盐具有一定的手性识别性能,可用于手性识别分离对映异构体。
本发明的有益效果在于:本发明提供了以联萘酚聚醚链为隔离基团、含有ent-贝叶烷骨架的手性分子钳,其在识别手性分子客体方面尤其是在识别D/L-氨基酸酯盐酸盐方面具有一定的应用前景;本发明所提供的以联萘酚聚醚链为隔离基团、以ent-贝叶烷结构为手性臂的分子钳具有原料易得、结构可调整、制备简洁等优点;故其有望在手性识别分离领域得到应用。
(四)具体实施方式
下面结合具体实施例对本发明进行进一步描述,但本发明的保护范围并不仅限于此:
实施例1:化合物(VIII)的制备
甜菊糖苷(VII)10g置于1000mL的圆底烧瓶中,缓慢加入10wt%的稀硫酸溶液600mL,磁力搅拌,油浴75℃。反应1h后,有少量黄色絮状固体产生,继续反应4h,停止反应冷却至室温。抽滤,将抽滤所得到的黄色固体转移至100mL的单口烧瓶中用丙酮重结晶,冷却放置,有白色晶体缓慢析出,过滤后干燥即得化合物(VIII)2.98g。产率:65.1%,熔点:263-264℃。1H-NMR(500MHz,CDCl3)δ(ppm):2.64(dd,J=18.6,3.8Hz,1H,15-Hα),2.17(d,J=13.4Hz,1H,3-Heq),1.89-1.79(m,3H,6-Heq,2-Hax,15-Hβ),1.74-1.66(m,3H,1-Heq,11-Heq,7-Heq),1.53(dd,J=11.5,2.8Hz,1H,14-Heq),1.50(dd,J=13.2,4.1Hz,1H,7-Hax),1.26(s,3H,18-CH3),0.98(s,3H,17-CH3),0.79(s,3H,20-CH3).IR3466,2943,2847,2678,1736,1694,1473,1405,1372,1320,1270,1177,982,773.
实施例2:化合物(IX)的制备
称取实施例1制备的化合物(VIII)(6.29mmol,2.0g)于50ml圆底烧瓶,向其中加入2ml二氯亚砜,70℃条件下反应1.5h,减压蒸馏蒸出多余的二氯亚砜,得褐色固体,向褐色固体中加入45ml的正己烷,回流10分钟,趁热抽滤得液体,静置以正己烷重结晶,得黄色固体即化合物(IX),产率44.5%。
实施例3:化合物(XIV)的制备
称取化合物(X)4.29g(15mmol),化合物(XII)7.47g(60mmol),碳酸钾5.94g(60mmol)和80mL DMF于250mL的单口烧瓶中。在110℃条件下搅拌反应24h,反应液冷却至室温后加水100mL,用50mL×4的二氯甲烷萃取,合并有机层用100mL×3的水洗涤。有机相用无水Na2SO4干燥,抽滤,取滤液减压旋干,硅胶柱层析(石油醚∶丙酮=2:1),产物为黄色油状化合物(XIV)5.20g(11.25mmol),收率75%。[α]D 20=+28.9(c 1.5,THF)。
实施例4:化合物(XV)的制备
以化合物(XIII)10.11g(60mmol)代替实施例3中的化合物(XII),其他操作同实施例3,得到黄色油状化合物(XV)5.03g(9.15mmol),收率61%。
实施例5:化合物(XVI)的制备
以化合物(XI)4.29g(15mmol)代替实施例3中的化合物(X),其他操作同实施例3,得到黄色油状化合物(XVI)5.75g(12.45mmol),收率83%。
实施例6:化合物(XVII)的制备
以化合物(XI)4.29g(15mmol)代替实施例3中的化合物(X),以化合物(XIII)10.11g(60mmol)代替实施例3中的化合物(XII),其他操作同实施例3,得到黄色油状化合物(XVII)5.94g(10.80mmol),收率72%。
实施例7:化合物(I)的制备
称取实施例2新鲜制备的化合物(IX)1.01g(3mmol),无水THF 25mL,NaOH固体0.10g(2.5mmol)于100mL的单口烧瓶中,迅速升温至回流,加入溶有实施例3制备的化合物(XIV)0.51g(1.2mmol)的无水THF溶液10mL,在油浴75℃条件下回流反应3.5h。反应液冷却至室温,抽滤,取滤液减压浓缩。硅胶柱层析(石油醚:丙酮=8:1),得白色固体化合物(I)0.687g(0.64mmol),收率53%。熔点:77-78℃.[α]D 20-31.38(c 5.00,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.95(d,J=9.0Hz,2H),7.86(d,J=8.1Hz,2H),7.42(d,J=9.0Hz,2H),7.35-7.32(m,2H),7.25-7.22(m,2H),7.18(d,J=8.4Hz,2H),4.10-4.08(m,4H),3.74-3.72(m,4H),3.45-3.42(m,4H),3.11-3.06(m,2H),3.02-2.98(m,2H),2.59(dd,J=18.5,3.7Hz,2H),2.13(d,J=13.3Hz,2H),1.83-1.80(m,2H),1.77-1.74(m,4H),1.68-1.66(m,6H),1.62-1.59(m,6H),1.54(dd,J=11.6,2.4Hz,2H),1.46(dd,J=13.5,3.6Hz,2H),1.42-1.39(m,4H),1.37-1.35(m,2H),1.29-1.26(m,2H),1.14(s,6H),1.09(dd,J=11.9,1.6Hz,2H),0.99(s,6H),0.93(dd,J=22.5,4.1Hz,2H),0.87(dd,J=13.0,4.1Hz,2H),0.64(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):222.3,177.1,154.3,134.1,129.5,129.4,127.9,126.4,125.5,123.8,120.7,115.8,70.2,69.5,69.0,63.1,57.2,54.8,54.4,48.7,48.5,43.8,41.6,39.9,39.5,38.0,37.9,37.4,28.9,21.6,20.4,19.9,18.9,13.3;HRMS(ESI):calcd.For C68H90N O10[M+NH4]1080.6559;found 1080.6598.2935,2847,1736,1621,1455,1233,1130,808,749.
实施例8:化合物(II)的制备
以实施例4制备的化合物(XV)0.66g(1.2mmol)代替实施例7中的化合物(XIV),其他操作同实施例7,得浅黄色油状化合物(II)0.75g(0.65mmol),收率54%。[α]D 20-28.39(c5.00,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.94(d,J=9.0Hz,2H),7.86(d,J=8.2Hz,2H),7.43(d,J=9.0Hz,2H),7.33-7.30(m,2H),7.24-7.21(m,2H),7.15(d,J=8.4Hz,2H),4.09(q,J=5.1Hz,4H),3.50-3.46(m,8H),3.18-3.16(m,4H),3.15-3.05(m,4H),2.62(dd,J=18.6,3.8Hz,2H),2.19-2.17(m,2H),1.89-1.86(m,2H),1.82-1.76(m,4H),1.73-1.68(m,6H),1.65-1.61(m,6H),1.55(dd,J=11.6,2.6Hz,2H),1.48(dd,J=13.6,3.9Hz,2H),1.43-1.40(m,4H),1.27-1.25(m,2H),1.19(s,6H),1.12(dd,J=12.1,2.0Hz,2H),1.02(dd,J=13.5,4.2Hz,2H),0.99(s,6H),0.93-0.87(m,4H),0.69(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):222.4,177.2,154.3,134.1,129.4,129.3,127.8,126.3,125.5,123.7,120.6,115.7,70.5,70.2,70.0,69.6,68.7,63.0,57.1,54.7,54.3,48.7,48.4,43.8,41.6,39.8,39.5,38.0,37.9,37.3,28.9,21.6,20.3,19.9,18.9,13.3;HRMS(ESI):calcd.For C72H94NaO12[M+Na+]1173.6637;found 1173.6635.IR3454,2934,2847,1736,1720,1508,807,748.
对比例:化合物(III)的制备
以实施例5制备的化合物(XVI)0.51g(1.2mmol)代替实施例7中的化合物(XIV),其他操作同实施例7,得白色固体化合物(III)0.74g(0.70mmol),收率58%。熔点:74-75℃.[α]D 20-65.89(c 5.00,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.95(d,J=9.0Hz,2H),7.86(d,J=8.2Hz,2H),7.43(d,J=9.1Hz,2H),7.35-7.32(m,2H),7.25-7.22(m,2H),7.18(d,J=8.3Hz,2H),4.11-4.08(m,4H),3.77-3.73(m,4H),3.48-3.43(m,4H),3.08-3.04(m,2H),3.02-2.98(m,2H),2.60(dd,J=18.5,3.7Hz,2H),2.13(d,J=13.4Hz,2H),1.79-1.75(m,4H),1.69-1.66(m,6H),1.63-1.59(m,6H),1.55(dd,J=11.7,2.6Hz,2H),1.46(dd,J=13.8,4Hz,2H),1.40(dd,J=11.4,3.7Hz,4H),1.38-1.35(m,2H),1.27-1.26(m,2H),1.24-1.20(m,2H),1.18-1.17(m,2H),1.13(s,6H),1.08(dd,J=12.1,1.9Hz,2H),0.99(s,6H),0.93(dd,J=21.5,4.2Hz,2H),0.87(dd,J=12.4,3.3Hz,2H),0.65(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):222.3,177.1,154.2,134.1,129.5,129.3,127.8,126.3,125.5,123.8,120.6,115.7,70.1,69.5,69.0,63.1,57.2,54.8,54.3,48.7,48.4,43.8,41.6,39.8,39.4,38.0,37.9,37.4,28.8,21.6,20.3,19.8,18.9,15.21,13.2;HRMS(ESI):calcd.For C68H90NO10[M+NH4]1080.6559;found 1080.6537.IR2951,2847,1736,1621,1455,1234,1131,808,749.
实施例9:化合物(IV)的制备
以实施例6制备的化合物(XVII)0.66g(1.2mmol)代替实施例7中的化合物(XIV),其他操作同实施例7,得浅黄色油状化合物(IV)0.83g(0.72mmol),收率60%。[α]D 20-65.89(c 5.00,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.94(d,J=9.0Hz,2H),7.86(d,J=8.2Hz,2H),7.43(d,J=9.0Hz,2H),7.34-7.31(m,2H),7.23-7.20(m,2H),7.16(d,J=8.5Hz,2H),4.11(d,J=5.0Hz,4H),4.09(q,J=5.1Hz,4H),3.52-3.44(m,8H),3.18-3.15(m,4H),3.14-3.05(m,4H),2.61(dd,J=18.6,3.8Hz,2H),2.19-2.17(m,2H),1.89-1.86(m,2H),1.82-1.76(m,4H),1.73-1.68(m,6H),1.64-160(m,6H),1.55(dd,J=11.6,2.6Hz,2H),1.48(dd,J=13.6,3.9Hz,2H),1.43-1.39(m,4H),1.28-1.26(m,2H),1.19(s,6H),1.12(dd,J=12.0,1.9Hz,2H),1.02(dd,J=13.5,4.2Hz,2H),0.99(s,6H),0.94-0.85(m,4H),0.70(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):222.4,177.2,154.4,134.1,129.4,129.3,127.8,126.3,125.5,123.7,120.6,115.7,70.5,70.2,70.0,69.6,68.8,63.0,57.1,54.7,54.3,48.7,48.5,43.8,41.6,39.8,39.5,38.0,37.9,37.3,28.9,21.6,20.3,19.9,18.9,13.3;HRMS(ESI):calcd.For C72H94Na O12[M+Na+]1173.6637;found 1173.6691.IR3452,2934,2847,1736,1720,1454,1237,1147,808,749.
实施例10:化合物(V)的制备
于50mL的单口烧瓶中依次加入按照实施例7方法制备的化合物(I)1.06g(1mmol),无水乙醇25mL,微微加热使其完全溶解后加入NaBH4固体0.19g(5mmol),室温下搅拌反应6h。向反应液中缓慢滴加水10mL左右淬灭反应,并用10%HCl调pH至中性,减压蒸去乙醇,用35mL×3的二氯甲烷萃取,合并有机层用30mL×3的水洗涤。有机相用无水Na2SO4干燥,抽滤,取滤液减压旋干得白色固体化合物(V)0.98g(0.92mmol),收率92%。熔点:87-88℃.[α]D 20-26.01(c 2.23,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.96(d,J=9.0Hz,2H),7.87(d,J=8.1Hz,2H),7.44(d,J=9.0Hz,2H),7.34(dd,J=8.1,6.7,1.2Hz,2H),7.24(ddd,J=7.9,6.7,1.2Hz,2H),7.18(d,J=8.4Hz,2H),4.13-4.06(m,4H),3.79-3.72(m,4H),3.50-3.42(m,4H),3.13-3.01(m,4H),2.19(s,2H),2.11(d,J=13.4Hz,2H),1.78-1.73(m,6H),1.70(dd,J=16.7,6.3Hz,6H),1.64(d,J=4.8Hz,6H),1.59-1.53(m,6H),1.49-1.43(m,2H),1.40-1.30(m,4H),1.28(dd,J=12.4,4.8Hz,6H),1.22(dd,J=6.7,5.3Hz,2H),1.12(d,J=4.5Hz,6H),1.05-1.00(m,4H),1.00-0.95(m,4H),0.92(s,6H),0.84(t,J=6.5Hz,2H),0.67(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):177.4,154.3,134.2,129.5,129.4,127.9,126.4,125.5,123.8,115.8,80.6,77.3,77.0,76.8,70.1,69.5,69.0,63.0,57.3,55.9,55.3,43.8,43.0,42.1,42.1,41.8,40.0,38.1,38.0,33.8,29.0,24.9,21.7,20.5,18.9,13.3;HRMS(ESI):calcd.For C68H94N O10[M+NH4]1084.6872;found 1084.6872.IR3504,2941,2845,1720,1622,1453,1263,1136,807,749.
实施例11:化合物(VI)的制备
以按照对比例方法制备的化合物(III)1.06g(1mmol)代替实施例10中的化合物(I),其他操作同实施例10,得白色固体化合物(VI)0.94g(0.88mmol),收率88%。熔点:75-76℃.[α]D 20-59.88(c 5.01,CH2Cl2);1H-NMR(500MHz,CDCl3)δ(ppm):7.95(d,J=9.0Hz,2H),7.87(d,J=8.1Hz,2H),7.44(d,J=9.0Hz,2H),7.34(ddd,J=8.1,6.7,1.1Hz,2H),7.26-7.21(m,2H),7.18(d,J=8.4Hz,2H),4.15-4.08(m,4H),3.86-3.75(m,4H),3.70(ddd,J=12.0,6.1,3.3Hz,2H),3.50-3.48(m,1H),3.48-3.42(m,4H),3.11-3.00(m,4H),2.12(d,J=13.2Hz,2H),2.06(s,1H),1.80-1.73(m,6H),1.72-1.65(m,6H),1.59(dd,J=8.3,5.0Hz,6H),1.56(d,J=5.0Hz,2H),1.49-1.44(m,2H),1.36(dd,J=12.1,4.8Hz,2H),1.31(dd,J=10.8,2.9Hz,2H),1.27(s,2H),1.22(dd,J=13.2,6.2Hz,4H),1.12(d,J=4.4Hz,6H),1.02(dd,J=12.8,3.9Hz,4H),1.00–0.98(m,2H),0.92(s,6H),0.87(dd,J=13.1,4.0Hz,2H),0.68(s,6H);13C-NMR(125MHz,CDCl3)δ(ppm):177.5,154.2,134.1,129.5,129.4,127.9,126.3,125.5,123.8,120.6,115.7,80.5,77.3,77.0,76.8,70.1,69。5,69.0,63.0,57.2,55.8,55.3,43.8,42.9,42.1,42.0,41.8,39.9,38.1,38.0,33.8,28.9,24.9,21.7,20.5,18.9,13.2;calcd.For C68H90Na O10[M+Na+]1089.6426;found 1089.6408.IR3461,2942,2845,1720,1622,1455,1263,1136,807,749.
实施例12:紫外分光光度计法测定识别性能
以甲醇作为溶剂,固定主体分子钳的浓度在2×10-5~9×10-5mol/L之间,不断加入客体分子(D-氨基酸甲酯盐酸盐或L-氨基酸甲酯盐酸盐),使其浓度在8×10-4-5×10- 3mol/L之间变化,采用同样浓度的客体溶液作参比,测定各组配合物溶液的吸光度值。实验过程中,随着加入客体化合物浓度增大,主体化合物特征吸收呈规律性上升,说明主体分子与客体分子之间存在着非共价键作用,产生了识别配合作用。主体分子钳(I)对所考察的氨基酸甲酯盐酸盐,当客体浓度远远大于主体浓度时,采用修饰的Benesi-Hildebrand方程进行线性拟合,以1/[G0]对1/ΔA作图,均给出了良好的线性关系,主客体间形成了1:1型超分子配合物,根据直线斜率和截距计算出的结合常数列于表1。
表1 25℃下甲醇溶液中主体分子钳(I)、(II)、(III)、(IV)、(V)、(VI)与客体分子的结合常数(Ka)和吉布斯自由能的(-ΔG0)变化情况
由表1可见合成的主体化合物(I)、(II)、(IV)、(V)、(VI)对D-和L-氨基酸酯盐酸盐均能形成超分子配合物,对手性苯甘氨酸甲酯盐酸盐具有很好的手性选择性,可利用主体化合物对一对手性对映异构体结合常数的差异,用其将D型和L型氨基酸酯的混合物分离开来,实现手性拆分。而化合物(III)虽然结构与其他化合物极为接近,但是其对手性苯甘氨酸甲酯盐酸盐却不具有手性选择性。
Claims (10)
1.联萘酚聚醚链桥连手性分子钳,其以手性联萘酚聚醚链为隔离基、以异斯特维醇为手性臂,结构如式(I)、式(II)、式(IV)、式(V)或式(VI)所示:
2.一种式(I)或式(II)或式(IV)所示的联萘酚聚醚链桥连手性分子钳的制备方法,所述的制备方法包括:
将式(IX)所示化合物、无水THF、NaOH固体置于反应容器中,迅速升温至回流,加入式(XIV)或式(XV)或式(XVII)化合物的无水THF溶液,在油浴30~100℃条件下反应1~10h,之后所得反应液b经后处理,制得相应的式(I)或式(II)或式(IV)所示的联萘酚聚醚链桥连手性分子钳;
3.如权利要求2所述的制备方法,其特征在于:所述式(IX)所示化合物与化合物(XIV)或式(XV)或式(XVII)、NaOH的物质的量之比为1:0.1~0.5:0.5~3;所述THF的体积用量以式(IX)所示化合物的质量计为10~40mL/g。
4.如权利要求2所述的制备方法,其特征在于:所述反应液b的后处理方法为:反应液b冷却至室温,抽滤,取滤液减压浓缩,经硅胶柱层析制得式(I)、(II)或(IV)所示的联萘酚聚醚链桥连分子钳化合物。
5.一种式(V)或式(VI)所示的联萘酚聚醚链桥连手性分子钳的制备方法,所述的制备方法包括:
(1)将式(IX)所示化合物、无水THF、NaOH固体置于反应容器中,迅速升温至回流,加入式(XIV)或式(XVI)化合物的无水THF溶液,在油浴30~100℃条件下反应1~10h,之后所得反应液b'经后处理,制得相应的式(I)或式(III)所示的手性分子钳;
(2)将式(I)或式(III)所示的手性分子钳溶于乙醇,加入过量NaBH4,在室温条件下反应4~8h,所得反应液c经后处理制得相应的式(V)或式(VI)所示的联萘酚聚醚链桥连手性分子钳;
6.如权利要求5所述的制备方法,其特征在于:步骤(1)中,所述式(IX)所示化合物与化合物(XIV)或式(XVI)、NaOH的物质的量之比为1:0.1~0.5:0.5~3;所述THF的体积用量以式(IX)所示化合物的质量计为10~40mL/g;
步骤(2)中,式(I)或式(III)所示化合物与NaBH4的物质的量之比为1:2~10;所述乙醇的体积用量以式(I)或(III)所示化合物的质量计为10~60mL/g。
7.如权利要求5或6所述的制备方法,其特征在于:所述反应液b'的后处理方法为:反应液b'冷却至室温,抽滤,取滤液减压浓缩,经硅胶柱层析制得式(I)或(III)所示的分子钳化合物。
8.如权利要求5或6所述的制备方法,其特征在于:所述反应液c的后处理方法为:反应结束后,向反应液中加水淬灭反应,用5wt%~20wt%HCl溶液中和,减压蒸去乙醇,CH2Cl2萃取,收集有机相,有机相依次经水洗、无水Na2SO4干燥、抽滤、滤液旋蒸除去溶剂,制得式(V)或式(VI)所示化合物。
9.结构如式(I)、式(II)、式(IV)、式(V)或式(VI)所示的联萘酚聚醚链桥连手性分子钳在识别手性分子客体中的应用,所述的手性分子客体为D/L-氨基酸酯盐酸盐;
10.如权利要求9所述的应用,其特征在于:所述的手性分子客体为D/L-苯甘氨酸甲酯盐酸盐。
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