CN100513395C - 一种制备多羟基环状硝酮的方法 - Google Patents
一种制备多羟基环状硝酮的方法 Download PDFInfo
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- CN100513395C CN100513395C CNB2006100666380A CN200610066638A CN100513395C CN 100513395 C CN100513395 C CN 100513395C CN B2006100666380 A CNB2006100666380 A CN B2006100666380A CN 200610066638 A CN200610066638 A CN 200610066638A CN 100513395 C CN100513395 C CN 100513395C
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Abstract
本发明公开了一种制备多羟基环状硝酮的方法。本发明所提供的制备式I结构的多羟基环状硝酮的方法,包括如下步骤:1)将式II结构的半缩醛与O-甲基羟胺盐酸盐在碱性条件下反应,得到式III结构的甲基肟醚;2)将式III结构的甲基肟醚与甲烷磺酰氯反应,得到式IV结构的甲磺酸酯;3)将式IV结构的甲磺酸酯在酸性条件下释放出醛基,得到式V结构的醛;4)式V结构的醛在碱性条件下,与羟胺盐酸盐作用,得到所述多羟基环状硝酮;其中,R1、R2和R3为烷基,链烯基,芳香基或取代芳基。本发明可以自然界广泛存在的糖为原料,经过几步反应制备具有高度反应活性的多羟基环状硝酮,实现了该类化合物的简洁、高效和大量制备。
Description
技术领域
本发明涉及一种多羟基环状硝酮的简便实用的制备方法。
背景技术
糖苷酶在生命体内扮演着重要的角色,它们参与了一系列重要的与糖轭合物有关的生物反应过程,如肠内的消化、糖蛋白的合成与分解、溶酶体(lysosomal)的糖轭合物的代谢等等,因此,它们与许多疾病密切相关。亚氨基糖已被证明是糖苷酶的有效抑制剂和治疗许多疾病的潜在药物[参见(a)Stütz,A.E.Iminosugars as GlycosidaseInhibitors:Nojirimycin and Beyond;Wiley-VCH:Weinheim,1999.(b)Asano,N.;Nash,R.J.;Molyneux,R.J.;Fleet,G.W.J.Tetrahedron:Asymmetry 2000,11,1645-1680.(c)Watson,A.A.;Fleet,G.W.J.;Asano,N.;Molyneux,R.J.;Nash,R.J.Phytochemistry2001,56,265-295.]。已经有许多亚氨基糖(如:NBDNJ,Miglitol)已经被开发成药物并且上市。
多羟基环状硝酮是制备亚氨基糖的有效中间体之一[参见:(a)Cicchi,S.;Marradi,M.;Vogel,P.;Goti,A.J.Org.Chem.2006,71,1614-1619.(b)Carmona,A.T.;Wightman,R.H.;Robina,I.;Vogel,P.Helv.Chim.Acta 2003,86,3066-3073.(c)Desvergnes,S.;Py,S.;Vallée,Y.J.Org.Chem.2005,70,1459-1462.(d)Holzapfel,C.W.;Crous,R.Heterocycles 1998,48,1337-1346.(b)Duff,F.J.;Vivien,V.;Wightman,R.H.Chem.Commun.2000,2127-2128.(c)Toyao,A.;Tamura,O.;Takagi,H.;Ishibashi,H.Synlett 2003,35-38.(d)Chevrier,C.;LeNouen,D.;Neuburger,M.;Defoin,A.;Tarnus,C.Tetrahedron Lett.2004,45,5363-5366.],但是已报道的多羟基环状硝酮的制备方法产率不高,效率低下,不能大量制备,这些都严重限制了该领域的研究以及新药开发的进程。一种常见的多羟基环状硝酮结构如式I,其中R1、R2和R3为甲基、乙基、丙基、丁基、烯丙基、苄基或对甲氧基苄基等。
发明内容
本发明的目的是提供一种简便、实用的制备多羟基环状硝酮方法。
本发明所提供的制备式I结构的多羟基环状硝酮的方法,包括如下步骤:
1)将式II结构的半缩醛与O-甲基羟胺盐酸盐在碱性条件下反应,得到式III结构的甲基肟醚;
2)将式III结构的甲基肟醚与甲烷磺酰氯反应,得到式IV结构的甲磺酸酯;
3)将式IV结构的甲磺酸酯在酸性条件下释放出醛基,得到式V结构的醛;
4)式V结构的醛在碱性条件下,与羟胺盐酸盐作用,得到所述多羟基环状硝酮;
(式II) (式III) (式IV) (式V)
(式I)
其中,R1、R2和R3为甲基、乙基、丙基、丁基、烯丙基、苄基或对甲氧基苄基等。
在上述反应过程中,碱可为有机碱或无机碱,常用有机碱为二乙胺、三乙胺、二异丙基胺、二异丙基乙基胺、吡啶、2,4,6-三甲基吡啶或四丁基氟化铵;常用无机碱为碳酸钠,碳酸氢钠,碳酸钾,碳酸氢钾,氢氧化钠,氢氧化钾或氟氢化钾。
步骤1)所述式II结构的半缩醛可由糖进行制备,所述糖为木糖、阿拉伯糖、核糖和来苏糖等。制备方法可参考文献进行[(a)Barker,R.;Fletcher,H.G.J.Org.Chem.1961,26,4605-4609.(b)Tejima,S.;Fletcher,H.G.J.Org.Chem.1963,28,2999-3004.]
步骤4)反应的溶剂为甲醇—水,乙醇—水,四氢呋喃,甲苯或者丙酮。反应的温度为0—100℃,反应时间为5分钟—2周。
本发明可以自然界广泛存在的糖为原料,经过几步反应制备具有高度反应活性的多羟基环状硝酮,实现了该类化合物的简洁、高效和大量制备。本发明所用原料为价格低廉的木糖、阿拉伯糖、核糖和来苏糖等各种糖,原料易得,制备方法简单,产率高,制备条件要求不高,且中间体的纯化容易简便。本方法易于实现大量合成,从而在短时间内合成大量亚氨基糖类化合物,为筛选有生物活性以及药用价值的化合物提供坚实的基础。
附图说明
图1、图2为(2R,3R,4R)-4-甲磺酰氧基-2,3,5-三苄氧基-1-戊醛的核磁共振氢谱和核磁共振碳谱图;
图3、图4为多羟基环状硝酮(2S,35,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯的核磁共振氢谱和核磁共振碳谱图;
图5、图6为(2S,3S,4R)-4-甲磺酰氧基-2,3,5-三苄氧基-1-戊醛的核磁共振氢谱和核磁共振碳谱图;
图7、图8为多羟基环状硝酮(2R,3R,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯的核磁共振氢谱和核磁共振碳谱图;
图9、图10为(2S,3S,4S,5S)-2-苄氧甲基-3,4-苄氧基-5-苯基-1-羟基吡咯烷的核磁共振氢谱、核磁共振碳谱图;
图11、图12、图13分别为(2S,3S,4S,5S)-2-羟甲基-3,4-二羟基-5-苯基吡咯烷的核磁共振氢谱、核磁共振碳谱图和二维核磁NOESY谱图。
具体实施方式
本发明首先将各种糖做成糖苷,糖环上的自由羟基用烷基保护,所得到的烷氧基糖苷进行脱保护变成半缩醛II,该半缩醛II以甲基肟醚的形式保护起来(III),游离的羟基转化为甲基磺酸酯IV,然后将甲基肟醚水解为醛V,在碱性条件下,该中间体醛V可高产率的转化成多羟基环状硝酮衍生物。中间体的纯化只是经过萃取和干燥,浓缩后的粗产物直接投入下一步反应,最后该硝酮就能从溶液中以固体形式析出来,或者经过柱色谱(硅胶)分离得到油状物。反应式如下:
该硝酮衍生物与格氏试剂反应,可高效的建立一个新的手性中心,且生成的羟胺能通过锌粉醋酸或者催化氢化条件被有效的还原而转化为亚氨基糖,从而实现了亚氨基糖的简洁,高效,经济实用而且通用的合成。例如,与金属试剂加成,生成羟胺VI,而化合物V经过一步或几步转化即可以合成出亚氨基糖VII,反应式如下:
实施例1、制备多羟基环状硝酮(2S,3S,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯I
根据文献方法[(a)Barker,R.;Fletcher,H.G.J.Org.Chem.1961,26,4605-4609.(b)Tejima,S.;Fletcher,H.G.J.Org.Chem.1963,28,2999-3003.]由D-木糖制备半缩醛2,3,5—O—三苄基—D—呋喃木糖II。将吡啶(30mL,0.37mol)加入该半缩醛粗品(按照0.2mol计算)的二氯甲烷(100mL)溶液中,往其中加入O-甲基羟胺盐酸盐(20.88g,0.25mol),室温搅拌12小时后,将溶剂蒸干,然后往浓缩液中加入乙酸乙酯和盐酸(1N,30mL),经过萃取分层,合并有机相,干燥,浓缩,得黄色油状物(2S,3S,4R)-2,3,5-三苄氧基-4-羟基-1-戊醛甲基肟醚III,直接投到下一步反应中。
将该黄色油状物(按照0.2mol计算)溶于二氯甲烷(100mL),加入吡啶(30mL,0.37mol)和甲烷磺酰氯(15.6mL,0.20mol),室温搅拌8小时后,加入盐酸(1N)淬灭该反应。经过萃取分层,合并有机相,干燥,浓缩,得黄色油状物(2S,3S,4R)-2,3,5-三苄氧基-4-甲基磺酰氧-1-戊醛甲基肟醚IV,直接用于下一步反应。
往该黄色油状物(按照0.2mol计算)的四氢呋喃(300mL)溶液中加入对甲基苯磺酸(38.00g,0.2mol)和37%甲醛水溶液(50mL),室温搅拌直到原料完全消失(TLC监测),然后往混合液中加入乙酸乙酯和水,经过萃取分层,合并有机相,干燥,浓缩,所得黄色油状物(2R,3R,4R)—4—甲磺酰氧基—2,3,5—三苄氧基—1—戊醛V,其核磁共振氢谱和碳谱分别如图1和图2所示。
先将碳酸氢钠(37.80g,0.45mol)加入盐酸羟胺(31.05g,0.45mol)的水(50mL)溶液中,加料过程中能观察到大量气泡产生。往其中加入上述黄色油状物(按照0.2mol计算)的乙醇(200mL)溶液,室温搅拌15小时,后加热搅拌48小时。然后往混合液中加入乙酸乙酯和水,经过萃取分层,合并有机相,干燥,浓缩,得黄色油状物。将该油状物溶于适当比例的乙酸乙酯和石油醚中,室温放置过夜,析出白色固体10.40g,母液继续结晶,又得到9.95g白色固体(2S,3S,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯I,母液经过柱色谱纯化后又得到白色固体1.35g,共计22.00g产物。以木糖为原料计算,七步反应总产率为26%。硝酮I的核磁共振氢谱和核磁共振碳谱图分别如图3和图4所示。
m.p.:90-91℃.
[α]D=+45°(c=0.4,CHCl3)
IR(cm-1):3049(w),2945,2923,2901,2884,2868,2851(w),1593(s),1551(s),1496(s),1452(s),1361(s),1247(vs),1131(vs),1247(vs),1028(vs).
1H-NMR(CDCl3):δ(ppm)7.38-7.26(m,15H),6.91(d,J=1.9Hz,1H),4.69-4.67(m,1H),4.64-4.46(m,6H),4.39(dd,J=3.2,2.2Hz,1H),4.10-4.04(m,2H),3.78(d,J=7.3Hz,1H);)
13C-NMR(CDCl3,75M):δ(ppm)66.03(CH2O),71.67,71.91,73.47,80.30(CHO),82.74(CHO),127.70,127.75,127.92,128.14,128.17,128.38,128.55,128.61,133.02(N=CH),137.06(C),137.16(C),137.63(C).
ESI-MS:m/z 440.3[M+Na]+,calcd for C26H27NO4
FT-ICRMS:m/z 418.2007[M+H]+(C26H28NO4requires 418.2013).
实施例2、制备多羟基环状硝酮(2R,3R,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯I
根据文献方法[(a)Barker,R.;Fletcher,H.G.J.Org.Chem.1961,26,4605-4609.(b)Tejima,S.;Fletcher,H.G.J.Org.Chem.1963,28,2999-3003.],由D-阿拉伯糖制备半缩醛2,3,5—O—三苄基—D—呋喃阿拉伯糖II。将吡啶(2.7mL,34.2mmol)加入该半缩醛(8.40g,11.4mmol)的二氯甲烷(20mL)溶液中,往其中加入O-甲基羟胺盐酸盐(1.91g,22.8mmol),室温搅拌24小时后,将溶剂蒸干,然后往浓缩液中加入乙酸乙酯和盐酸(1N,30mL),经过萃取分层,合并有机相,干燥,浓缩,所得粗产物经过柱色谱纯化后得到淡黄色油状物(2R,3R,4R)-2,3,5-三苄氧基-4-羟基-1-戊醛甲基肟醚III(8.20g,产率91%)。
将仲醇(7.34g,16.3mmol)溶于二氯甲烷(30mL),加入吡啶(5mL,62mmol)和甲烷磺酰氯(1.9mL,24mmol),室温搅拌8小时后,加入盐酸(1N)淬灭该反应。经过萃取分层,合并有机相,干燥,浓缩,得黄色油状物(2R,3S,4R)-2,3,5-三苄氧基-4-甲基磺酰氧基-1-戊醛甲基肟醚IV(9.35g),直接用于下一步反应中。
往黄色油状物(6.94g,13mmol)的四氢呋喃(50mL)溶液中加入对甲基苯磺酸(4.95g,26mmol)和37%甲醛水溶液(5mL),室温搅拌直到原料完全消失(TLC监测),然后往混合液中加入乙酸乙酯和水,经过萃取分层,合并有机相,干燥,浓缩,所得黄色油状物(2S,3S,4R)—4—甲磺酰氧基—2,3,5—三苄氧基—1—戊醛V(6.83g),直接投到下一步反应中。其核磁共振氢谱和核磁共振碳谱图分别如图5和图6所示。
先将碳酸氢钠(3.36g,40mmol)加入盐酸羟胺(2.08g,30mol)的水(10mL)溶液中,加料过程中能观察到大量气泡产生。往其中加入上述黄色油状物的甲醇(30mL)溶液,室温搅拌1小时,后加热搅拌32小时。然后往混合液中加入乙酸乙酯和水,经过萃取分层,合并有机相,干燥,浓缩,得黄色油状物。将该油状物通过柱色谱纯化后得到淡黄色油状物,(2R,3R,4S)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯I(1.62g,三步产率30%)。其核磁共振氢谱和核磁共振碳谱图分别如图7和图8所示。(该硝酮的另一种合成法见:Cicchi,S.;Marradi,M.;Vogel,P.;Goti,A.J.Org.Chem.2006,71,1614-1619.)
1H-NMR(CDCl3,300MHz):δ(ppm)7.57-7.31(m,15H),6.85(s,1H),4.80-4.78(m,1H),4.72-4.52(m,6H),4.40(dd,1H,J=4.6 and 7.6Hz),4.19(br s,1H),4.01(dd,1H,J=4.3 and 10.1Hz),3.86(d,J=9.9Hz).
13C-NMR(CDCl3,75MHz):δ(ppm)137.92,137.33,137.25,133.45,128.66,128.58,128.35,128.24,128.12,127.99,127.86,127.61,83.22,80.64,74.18,73.60,73.19,72.51,64.48.
DEPT 135(CDCl3,75MHz):δ(ppm)positive 133.44,128.65,128.58,128.35,128.23,128.11,127.98,127.86,127.61,83.21,80.64,74.19;negative 73.60,73.19,72.50,64.49.
实施例3:硝酮与苯基溴化镁的加成反应得到(2S,3S,4S,5S)-2-(苄氧甲基)-3,4-二苄氧基-5-苯基-N-羟基吡咯烷VI
氮气保护条件下,将溴苯(0.26mL,2.5mmol)加入镁条(60mg,2.5mmol)和新蒸四氢呋喃(5mL)的悬浮液中,加热回流3个小时制备苯基溴化镁的四氢呋喃溶液。在冰浴条件下,往盛有剧烈搅拌着的硝酮(2R,3R,4R)-2-苄氧甲基-3,4-二苄氧基-3,4-二氢-1-氧吡咯(200mg,0.5mmol)的四氢呋喃溶液的烧瓶中逐滴加入如上方法所制备的格氏试剂,加料完毕后继续搅拌半小时。然后加入饱和氯化铵水溶液淬灭该反应,加入乙酸乙酯萃取,合并有机相。将溶剂在真空条件下旋干,所得粗产品经过柱层析纯化,得无色油状物,经室温放置后变成白色固体(216mg,产率91%),其核磁共振氢谱和碳谱分别如图9和图10所示。
m.p.81-82℃.
[α]X=+16.8°(c=2.5,CHCl3)
IR(cm-1):3343(w),3107(w),3087(w),3063(w),3031(w),2971(w),2870(w),1604(w),1595(w),1496(w),1472(w),1454(m),1365(w),1098(s),1076(vs).
1H-NMR(CDCl3):δ(ppm):3.69-3.75(m,1H),3.78(t,1H,J=7.2Hz),3.89(dd,1H,J=3.7and 8.7Hz),4.06(dd,1H,J=3.4 and7 .2Hz),4.11(dd,1H,J=2.7 and 3.2Hz),4.23(d,1H,J=7.2Hz),4.33(ABQ,2H,J=11.8Hz),4.55(ABQ,2H,J=12.0Hz),4.56(ABQ,2H,J=12.1Hz),4.94(s,1H,OH),7.07-7.44(m,20H).
1H-NMR(CDCl3+D2O):δ(ppm):3.73-3.77(m,1H),3.80(t,1H,J=7.2Hz),3.93(dd,1H,J=3.9 and 8.9Hz),4.09(dd,1H,J=3.4 and 7.2Hz),4.14(dd,1H,J=2.8and 3.2Hz),4.26(d,1H,J=7.2Hz),4.37(ABQ,2H,J=11.9Hz),4.60(s,2H),4.58(ABQ,2H,J=12.0Hz),7.12-7.47(m,20H).
DEPT-135(CDCl3,75M):δ(ppm)positive:128.50,128.38,128.34,128.23,128.05,127.78,127.69,127.67,127.62,127.56,87.49,83.68,74.06,68.93.negative:73.44,72.01,71.66,66.86.
13C-NMR(CDCl3,75M):δ(ppm)139.36,138.25,138.11,137.89,128.49,128.38,128.34,128.23,128.05,127.77,127.69,127.67,127.61,127.55,87.50,83.69,74.07,73.44,72.01,71.66,68.93,66.87.
ESI-MS:m/z 496.5[M+H]+;
FT-ICRMS:m/z 496.2485[M+H]+,(C32H33NO4requires 496.2482).
实施例4:硝酮与对10-烯-十一烷基溴化镁的加成(2S,3S,4S,5S)-2-苄氧甲基-3,4-二苄氧基-5-(10-烯-十一烷基)-N-羟基吡咯烷VI
氮气保护条件下,将11-溴-1-烯(0.4mL,2.4mmol)加入镁条(40mg,2.4mmol)和新蒸乙醚(5mL)的悬浮液中,加热回流30分钟制备10-烯-十一烷基溴化镁的乙醚溶液。在冰浴条件下,往盛有剧烈搅拌着的硝酮(100mg,0.2mmol)的四氢呋喃溶液的烧瓶中逐滴加入如上方法所制备的格氏试剂,加料完毕后继续搅拌半小时。然后加入饱和氯化铵水溶液淬灭该反应,加入乙酸乙酯萃取,合并有机相。将溶剂在真空条件下旋干,所得粗产品经过柱层析纯化,得无色油状物(120mg,产率86%).
实施例5:经过催化氢化脱保护得到亚氨基糖(2S,3S,4S,5S)-2-羟甲基-3,4-二羟基-5-苯基吡咯烷VII
往(2S,3S,4S,5S)-2-(苄氧甲基)-3,4-二苄氧基-5-苯基-N-羟基吡咯烷(200mg,0.4mmol)的二氯甲烷溶液中加入甲醇(10mL)和盐酸(6N,1mL)和10%钯/碳(10%,60mg)。利用氮气赶去反应体系中的氧气,然后用氢气充满该反应体系。室温搅拌20小时后,TLC(EA/MeOH:5/1)表明原料已经完全消失,生成了大极性的物种。用氮气赶去反应体系中的氢气,将催化剂滤掉,滤液在真空条件下浓缩。粗产物重新溶解于甲醇,并用浓氨水中和,经过真空条件出去多余的氨气后,剩余物用少量蒸馏水溶解并转移到预先处理好的离子交换树脂上。经过处理后得到目标化合物(2S,3S,4S,5S)-2-羟甲基-3,4-二羟基-5-苯基吡咯烷(72mg,产率85%),其核磁共振氢谱和碳谱分别如图11和图12所示,其二维核磁NOESY谱图如图13所示。
[α]D=-52°(c=0.65,H2O)
1H-NMR(D2O,300M):δ(ppm):7.41(m,5H),4.09(dd,1H,J=7.4 and 8.3Hz),3.93(broad t,2H),3.72(dd,1H,J=4.7 and 11.6Hz),3.65(dd,1H,J=6.3 and 11.6Hz),3.22(dd,1H,J=6.3 and 11.5Hz).
1H-NMR(D2O,600M):δ(ppm):7.36(broad d,4H,H-2’,H-3’,H-5’,H-6’),7.32-7.27(m,1H,H-4’),4.04(dd,1H,J=7.5 and 9.0Hz,H-4),3.88(d,1H,J=5.6Hz,H-3or H-5),3.87(d,1H,J=7.4Hz,H-5 or H-3),3.67(dd,1H,J=4.5 and 11.6Hz,H-1a),3.61(dd,1H,J=6.5 and 11.6Hz,H-1b),3.17(dd,1H,J=2.1 and 6.8Hz,H-2).
DEPT-135(D2O,75M):δ(ppm)positive:128.95,128.23,127.35,82.26,77.51,64.00,61.79.negative:62.46.
13C-NMR(D2O,75M):δ(ppm)139.73,128.96,128.23,127.36,82.27,77.53,64.01,62.47,61.81.
ESI-MS:m/z 210.2[M+H]+,232.2[M+Na]+.
FT-ICRMS:m/z 210.1126[M+H]+,(C11H16NO3requires 210.1125).
实施6:经过催化氢化脱保护得到亚氨基糖(2S,3S,4S,5S)-2-羟甲基-3,4-二羟基-5-十二烷基吡咯烷盐酸盐VII
往(2S,3S,4S,5S)-2-苄氧甲基-3,4-二苄氧基-5-(10-烯-十一烷基)-N-羟基吡咯烷(100mg,1.7mmol)的二氯甲烷(10mL)溶液中加入甲醇(10mL)和一滴浓盐酸和10%钯/碳(20mg)。利用氮气赶去反应体系中的氧气,然后用氢气充满该反应体系。室温搅拌直到TLC(EA/MeOH:5/1)表明原料已经完全消失,生成了大极性的物种。用氮气赶去反应体系中的氢气,将催化剂滤掉,滤液在真空条件下浓缩。粗产物重新溶解于甲醇和乙酸乙酯中,静置后得到白色固体(5mg),母液浓缩后得到棕色固体物(37mg),共计得到42mg目标化合物(2S,3S,4S,5S)-2-羟甲基-3,4-二羟基-5-十一烷基-吡咯烷,产率88%。
1H-NMR(D2O,600M):δ(ppm):3.90(t,1H,J=7.1and7.4Hz),3.80(t,1H,J=7.6and 7.1Hz),3.77(dd,1H,J=3.7,3.6 and 12.7,12.6Hz),3.70(dd,1H,J=6.1 and 12.7Hz),3.41-3.38(m,1H),3.26(dd,1H,J=8.3 and 14.4Hz),1.77-1.71(m,1H),1.63-1.56(m,1H),1.29-1.12(m,18H),0.70(t,3H,J=6.7 and 7.1Hz)
13C-NMR(D2O):δ(ppm):78.1(OCH),74.2(OCH),62.1(OCH2),61.5(NCH),57.9(NCH),31.2,30.1,28.7,28.6,28.5,28.3,28.2,25.1,22.0,13.4.
Claims (5)
2、根据权利要求1所述的方法,其特征在于:所述碱为有机碱或无机碱,所述有机碱为二乙胺、三乙胺、二异丙基胺、二异丙基乙基胺、吡啶、2,4,6-三甲基吡啶或四丁基氟化铵;所述无机碱为碳酸钠、碳酸氢钠、碳酸钾、碳酸氢钾、氢氧化钠、氢氧化钾或氟氢化钾。
3、根据权利要求1或2所述的方法,其特征在于:步骤1)所述式II结构的半缩醛由糖进行制备,所述糖为木糖、阿拉伯糖、核糖或来苏糖。
4、根据权利要求1或2所述的方法,其特征在于:步骤4)反应的溶剂为甲醇—水、乙醇—水、四氢呋喃、甲苯或者丙酮。
5、根据权利要求1或2所述的方法,其特征在于:步骤4)反应的温度为0—100℃,反应时间为5分钟—2周。
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