CN108033985B - 一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法 - Google Patents
一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法 Download PDFInfo
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Abstract
本发明公开了一种乙酰化δ‑羟基‑α,β‑不饱和糖醛的合成方法，其特点是将保护基的糖烯与有机溶剂和水按1 mol:50~250 L:0.6~2.8 L的摩尔体积比混合，以FeCl3为催化剂进行开环反应，其产物与三乙胺、DMAP和乙酸酐按1:1~3:0.1~0.5:0.5~3.0摩尔比混合，在0~45oC温度下进行乙酰化反应，反应结束后经中和、萃取和提纯，得到不同保护基的乙酰化δ‑羟基‑α,β‑不饱和糖醛。本发明与现有技术相比具有工艺简单，操作方便，试剂无毒性且价格经济，反应条件温和、速度快，收率高，是一种绿色环保、经济高效且很有应用前景的乙酰化Perlin醛合成的新方法。
Description
技术领域
本发明涉及有机合成中间体技术领域，具体地说是一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法。
背景技术
由于糖类分子中含有多个羟基和多个固有的手性中心，以及糖类在自然界中的广泛存在，使得糖类分子及其衍生物广泛地用于合成天然产物和许多具有重要生物活性的化合物，糖类分子及其衍生物在合成中的应用被越来越多的化学家所关注。Perlin醛，又叫δ-羟基-α,β-不饱和糖醛，是一类非常重要的有机中间体，这类分子中含有羟基，醛基和共轭双键等多个官能团，可以进行有关羟基的相关反应，如可以将羟基进行保护和脱保护，将羟基进行氧化，将羟基进行氨基化(Mitsunobu reaction)等等；共轭双键的存在使该分子还可以作为Michael受体，可以进行加氢还原，环氧化，成环反应等等。该分子还可以进行一系列有关醛基的反应，如Wittig反应，与格氏试剂反应，还原，氧化，羟醛缩合反应(Aldolreaction)等等。已经有文章报道了用苄基保护的半乳糖烯或葡萄糖烯开环后的Perlin醛来合成鞘氨醇及其类似物的方法。(Kokatla,H.P.；Sagar,R.；Vankar,Y.D.TetrahedronLett.2008,49,4728)
Perlin在1975年提出使用2mol％的硫酸汞和5mM浓硫酸在1,4-二氧六环中反应24个小时得到乙酰基保护的葡萄糖开环后的δ-羟基-α,β不饱和醛。(Gonzalez,F.；Lesage,S.；Perlin,A.S.Carbohydr.Res.1975,42,267)但他们只合成了乙酰基保护的葡萄糖，半乳糖和阿拉伯糖三种糖烯开环的δ-羟基-α,β不饱和醛。2004年，Shaw小组对该方法进行了进一步的研究，在10mol％的硫酸汞和0.02N浓硫酸作用下，以1,4-二氧六环或四氢呋喃作溶剂，在室温下可以制备甲基保护的的葡萄糖、半乳糖、阿拉伯糖糖烯和苄基保护的半乳糖烯开环得到的Perlin醛。(Sagar,R.；Pathak,R.；Shaw,A.K.Carbohydr.Res.2004,339,2031)但该类方法都使用到毒性很大的硫酸汞，对环境污染大，且反应时间长。2006年Shaw小组又发明了一种无汞的合成Perlin醛的方法，在使用ZnI和HfCl4共同催化下，以乙腈和水(体积比7:3)为溶剂，在140℃的温度下反应，以中等到较好的产率得到了相应的Perlin醛。(Saquib,M.；Sagar,R.；Shaw,A.K.Carbohydr.Res.2006,341,1052)虽然该方法避免了高毒性的硫酸汞，但反应温度很高，且需要两种昂贵金属催化剂共同作用才能得到目标产物。2011年Ramesh以InCl3为催化剂，合成了乙酰化葡萄糖和乙酰化半乳糖开环后的Perlin醛，得到的Perlin醛是含4位羟基或5位羟基两个化合物的混合物，经过对羟基酰化后以总产率60％左右得到目标产物(Nagaraj,P.；Ganesan,M.；Ramesh,N.G.Tetrahedron 2011,67,769)但反应时间要在5-7h,适用范围有限，且用到价格昂贵且有毒的InCl3为催化剂。
综上所述，现有技术的Perlin醛合成工艺复杂，反应条件苛刻，产率低，，原料用量大且有毒，生产成本高，严重制约这类分子的广泛应用。
发明内容
本发明的目的是针对现有技术的不足而提供的一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，采用乙酰基、苯甲酰基或苄基保护的糖烯与有机溶剂混合，在FeCl3或FeCl3·6H2O催化剂下进行开环反应，制得的开环产物直接用于下一步酰化反应，进行一锅法合成乙酰化Perlin醛，工艺简单，操作方便，使用无毒性且价格经济的铁试剂，反应条件温和，反应速度快，收率高，是一种绿色环保、经济高效且很有应用前景的乙酰化Perlin醛合成的新方法。
实现本发明目的的具体技术方案是：一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特点是将保护基的糖烯与有机溶剂和水按1mol:50～250L:0.6～2.8L的摩尔体积比混合，以FeCl3或FeCl3·6H2O为催化剂进行开环反应，其反应产物与三乙胺、DMAP和乙酸酐按1:1～3:0.1～0.5:0.5～3.0摩尔比混合，在0～45℃温度下进行乙酰化反应，反应结束后经中和、萃取和提纯，得到不同保护基的乙酰化δ-羟基-α,β-不饱和糖醛，所述开环反应温度为20～95℃；所述糖烯与催化剂摩尔比为1:0.1～1.0；所述糖烯为葡萄糖烯、半乳糖烯、鼠李糖烯、木糖烯、阿拉伯糖烯、纤维二糖、乳糖烯或麦芽糖烯；所述有机溶剂为乙腈、丙酮、1,4-二氧六环、二氯甲烷或二氯乙烷；所述保护基为乙酰基、苯甲酰基或苄基。
所述糖烯与有机溶剂和水的体积摩尔比优选为1mol:150～200L:1.7～2.2L。
所述糖烯与催化剂的摩尔比优选为1:0.3～0.5。
所述开环反应温度优选为60～80℃。
所述有机溶剂优选为乙腈。
本发明与现有技术相比具有工艺简单，操作方便，试剂无毒性且价格经济，反应条件温和、速度快，收率高，可广泛应用于工业化大规模生产，是一种绿色环保、经济高效且很有应用前景的乙酰化Perlin醛合成的新方法。
具体实施方式
本发明按如下反应结构式进行乙酰化Perlin醛的一锅法合成反应：
其中：R＝CH2OAc、CH2OBz、CH2OBn、CH2OGlycosyl、CH3或H；R1＝OAc、OBz、OBn、H或OGlycosyl；R2＝OAc、OBz或OBn。
以下将通过具体的实施例对本发明做进一步的阐述：
实施例1
在烧瓶中加入40.8mg(0.15mmol)全乙酰化葡萄糖烯，20mL丙酮和1mL水，放入50℃温度的油浴中搅拌，随后加入24.2mg(0.090mmol)FeCl3·6H2O催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，并用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入31.4μl三乙胺、1.8mg DMAP和19μl乙酸酐，在35℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物为乙酰化保护基的Perlin葡萄糖醛35.5mg，其产率为87％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-4,5,6-三-O-乙酰基-2,3-二脱氧醛-D-赤式-2-己糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.59(d,J＝7.6Hz,1H),6.72(dd,J＝15.8,5.2Hz,1H),6.28(ddd,J＝15.8,7.6,1.5Hz,1H),5.76(td,J＝5.0,1.5Hz,1H),5.28(ddd,J＝6.3,4.8,4.0Hz,1H),4.27(dd,J＝12.2,3.8Hz,1H),4.20(dd,J＝12.2,6.4Hz,1H),2.14(s,3H),2.09(s,3H),2.06(s,3H)。
MS(ESI):m/z Calculated for[M+Na]+C12H16O7Na 295.08,found 295.08。
实施例2
在烧瓶中加入全乙酰化鼠李糖烯32.1mg(0.15mmol)、30mL二氯甲烷和1mL水，在25℃温度的油浴中搅拌，随后加入2.5mg(0.015mmol)FeCl3催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入25μl三乙胺、5mg DMAP和17μl乙酸酐，在0℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物为乙酰化保护基的Perlin鼠李糖醛19.8mg，其产率为61％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-4,5-二-O-乙酰基-2,3-二脱氧醛-L-赤式-2-己糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.59(d,J＝7.7Hz,1H),6.72(dd,J＝15.8,5.1Hz,1H),6.27(ddd,J＝15.8,7.7,1.6Hz,1H),5.64(ddd,J＝5.2,3.7,1.6Hz,1H),5.16(qd,J＝6.6,3.7Hz,1H),2.14(s,3H),2.05(s,3H),1.96–1.74(m,1H),1.25(d,J＝6.6Hz,3H).。
MS(ESI):m/z Calculated for[M+Na]+C12H16O5Na 239.09,found 239.10。
实施例3
在烧瓶中加入30.0mg(0.15mmol)全乙酰化阿拉伯糖烯，30mL乙腈和0.5mL水，放入80℃温度的油浴中搅拌，随后加入15.1mg(0.09mmol)FeCl3催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入35μl三乙胺、3mg DMAP和19μl乙酸酐，在15℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物乙酰化保护基的Perlin阿拉伯糖醛26.4mg，其产率为88％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-4,5-二-O-乙酰基-2,3-二脱氧醛-D-甘油基-2-戊糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.58(d,J＝7.7Hz,1H),6.72(dd,J＝15.9,4.7Hz,1H),6.29(ddd,J＝15.9,7.7,1.5Hz,1H),5.77–5.69(m,1H),4.35(dd,J＝11.9,4.0Hz,1H),4.20(dd,J＝11.9,6.0Hz,1H),2.14(s,3H),2.07(s,3H)。
MS(ESI):m/z Calculated for[M+Na]+C9H12O5Na 223.06,found 223.17。
实施例4
在烧瓶中加入68.7mg(0.15mmol)全苯甲酰化葡萄糖烯，35mL1，4-二氧六环和0.7mL水，放入70℃温度的油浴中搅拌，随后加入36mg(0.12mmol)FeCl3·6H2O催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入45μl三乙胺、5mg DMAP和100μl乙酸酐，在45℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物乙酰化保护基的Perlin葡萄糖醛51.1mg，其产率为86％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-5-O-乙酰基-4,6-二-O-苯甲酰基-2,3-二脱氧醛-D-赤式-2-己糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.59(d,J＝7.6Hz,1H),8.09-8.05(m,2H),8.02–7.98(m,2H),7.61(dt,J＝21.6,7.4Hz,2H),7.47(dt,J＝18.3,7.8Hz,4H),6.89(dd,J＝15.8,4.9Hz,1H),6.39(ddd,J＝15.8,7.6,1.5Hz,1H),6.14(td,J＝4.8,1.5Hz,1H),5.59(dt,J＝6.2,4.4Hz,1H),4.70(dd,J＝12.1,4.1Hz,1H),4.51(dd,J＝12.1,6.4Hz,1H),2.12(s,3H).13C NMR(125MHz,CDCl3):δ192.32,170.11,166.12,165.08,148.27,134.04,133.76,133.62,130.0(2C),129.85(2C),129.37,128.87(2C),128.71(2C),128.56,71.33,71.31,62.05,20.95。
MS(ESI):m/z Calculated for[M+Na]+C22H20O7Na 419.11,found 419.17。
实施例5
在烧瓶中加入62.4mg(0.15mmol)全苄基保护的葡萄糖烯，15mL二氯乙烷和0.5mL水，放入80℃温度的油浴中搅拌，随后加入5mg(0.09mmol)FeCl3催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入12μl三乙胺、1.8mg DMAP和32μl乙酸酐，在35℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物乙酰化保护基的Perlin葡萄糖醛35.9mg，其产率为65％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-5-O-乙酰基-4,6-二-O-苄基-2,3-二脱氧醛-D-赤式-2-己糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.56(d,J＝7.8Hz,1H),7.35–7.26(m,10H),6.73(dd,J＝15.8,6.3Hz,1H),6.31(ddd,J＝15.8,7.8,1.2Hz,1H),5.18(dd,J＝9.8,5.4Hz,1H),4.61–4.45(m,4H),4.40–4.36(m,1H),3.72(dd,J＝10.7,5.3Hz,1H),3.62(dd,J＝10.7,4.2Hz,1H),2.04(s,3H).。
MS(ESI):m/z Calculated for[M+Na]+C22H24O5Na 319.15,found 319.25。
实施例6
在烧瓶中加入84.0mg(0.15mmol)全乙酰化的麦芽糖烯，10mL乙腈和0.2mL水，放入90℃温度的油浴中搅拌，随后加入36mg(0.12mmol)FeCl3·6H2O催化剂，TLC监测反应，直至原料反应完，将反应液冷却至室温后加水淬灭反应，用DCM萃取后合并有机相，用饱和NaCl溶液洗涤后经干燥、浓缩得Perlin醛，在开环反应的产物中加入5mLDCM，随后依次加入50μl三乙胺、8mg DMAP和45μl乙酸酐，在40℃温度下进行乙酰化反应，TLC监测反应至原料反应完，加入饱和NH4Cl溶液淬灭反应，用DCM萃取后经干燥、柱层析后得到纯的产物乙酰化保护基的Perlin麦芽糖醛57mg，其产率为68％。
上述所得产物经核磁波谱检测和质谱分析后可以确定目标产物结构为(2E)-4-O-(2’,3’,4’,6’-四-O-乙酰基-α-D-吡喃葡萄糖基)-5,6-二-O-乙酰基-2,3-二脱氧醛-D-赤式-2-己糖，其结构表征数据如下：
1H NMR(500MHz,CDCl3)δ9.61(d,J＝7.7Hz,1H),6.66(dd,J＝15.8,5.3Hz,1H),6.42(ddd,J＝15.8,7.7,1.3Hz,1H),5.48–5.42(m,1H),5.26(dt,J＝7.5,3.8Hz,1H),5.13–5.08(m,1H),4.99(d,J＝3.8Hz,1H),4.94(dd,J＝10.3,3.8Hz,1H),4.63–4.59(m,1H),4.42(dd,J＝12.3,3.5Hz,1H),4.30(dd,J＝12.4,4.1Hz,1H),4.24–4.19(m,2H),4.08(dd,J＝12.4,2.3Hz,1H),2.12(s,3H),2.11(s,3H),2.10(s,3H),2.08(s,3H),2.05(s,3H),2.02(s,3H).13C NMR(125MHz,CDCl3):δ192.03,170.72,170.55,170.13(2C),170.00,169.64,148.65,135.03,95.33,76.12,71.71,70.37,69.81,68.37,68.29,61.64,61.43,21.03,20.86,20.82,20.79,20.76,20.75。
MS(ESI):m/z Calculated for[M+Na]+C24H32O15Na 583.16,found 583.17。
从上述各实例可以得知，本发明能够适应于乙酰基、苯甲酰基和苄基保护的糖烯开环并一锅乙酰化合成相应的乙酰化Perlin醛，具有时间短、反应快、产率高等优点。以上只是对本发明作进一步的说明，并非用以限制本专利，凡为本发明等效实施，均应包含于本专利的权利要求范围之内。
Claims (5)
1.一种乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特征在于将保护基的糖烯与有机溶剂和水按1 mol:50~250 L:0.6~2.8 L的摩尔体积比混合，以FeCl3或FeCl3·6H2O为催化剂进行开环反应，其反应产物与三乙胺、DMAP和乙酸酐按1:1~3:0.1~0.5 :0.5~3.0摩尔比混合，在0~45oC温度下进行乙酰化反应，反应结束后经中和、萃取和提纯，得到不同保护基的乙酰化δ-羟基-α,β-不饱和糖醛，所述开环反应温度为20~95 oC；所述糖烯与催化剂摩尔比为1:0.1~1.0；所述糖烯为葡萄糖烯、半乳糖烯、鼠李糖烯、木糖烯、阿拉伯糖烯、纤维二糖、乳糖烯或麦芽糖烯；所述有机溶剂为乙腈、丙酮、1,4-二氧六环、二氯甲烷或二氯乙烷；所述保护基为乙酰基、苯甲酰基或苄基。
2.根据权利要求所述乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特征在于所述糖烯与有机溶剂和水的体积摩尔比为1 mol:150~200L:1.7~2.2 L 。
3.根据权利要求所述乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特征在于所述糖烯与催化剂的摩尔比为1 :0.3~0.5。
4.根据权利要求所述乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特征在于所述开环反应温度为60~80 oC。
5.根据权利要求所述乙酰化δ-羟基-α,β-不饱和糖醛的合成方法，其特征在于所述有机溶剂为 乙腈。
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| CN106117283A (zh) * | 2016-07-06 | 2016-11-16 | 华东师范大学 | 一种5‑羟甲基糠醛参与的2,3‑不饱和糖苷的合成方法 |
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| CN106117283A (zh) * | 2016-07-06 | 2016-11-16 | 华东师范大学 | 一种5‑羟甲基糠醛参与的2,3‑不饱和糖苷的合成方法 |
Non-Patent Citations (5)
| Title |
|---|
| ENANTIPECIFIC SYNTHESIS OF 14S,15S LEUKOTRIENE A4 METHYL ESTER;A V Rama Rao,et al.;《Bioorganic & Medicirwl Chemwrry Lefrers》;19111123;第1卷(第4期);第201-204页 * |
| InCl3-CH3CN-H2O: an efficient catalyst-solvent combination for the synthesis of Perlin aldehydes and related compounds. Application in the synthesis of unnatural L-azasugars;Paramathevar Nagaraj,et al.;《Tetrahedron》;20101118;第67卷;第769-776页 * |
| Lewis acid-surfactant-combined catalyzed synthesis of 4-aminocyclopentenones from glycals in water;Wang, Siming，et al.;《Green Chemistry》;20131231;第15卷;第3180-3183页 * |
| Stereoselective synthesis of safingol and its natural stereoisomer from D-glycals;Hari Prasad Kokatla,et al.;《Tetrahedron Letters》;20080613;第49卷;第4728-4730页 * |
| Synthesis of (-)-Deoxoprosophylline, (+)-2-epi-Deoxoprosopinine, and (2R,3R)- and (2R,3S)-3-Hydroxypipecolic Acids from D-Glycals;Hari Prasad Kokatla,et al.;《J. Org. Chem.》;20100604;第75卷;第4608-4611页 * |
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