CN113185549A - 一种Wittig-Horner试剂的制备方法 - Google Patents
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Abstract
本发明提供的Wittig‑Horner试剂的制备方法通过将式(I)结构的化合物与特定浓度的乙醛酸水溶液在甲苯中加热反应。结果发现,本发明在比较低的温度下原料可完全转化,且其得到的产品纯度高,直接过滤、打浆即可进行后续反应,进一步得到关键中间体式(III)结构的化合物,反应条件温和,且总收率高达80%以上。
Description
技术领域
本发明涉及药物合成领域,尤其涉及一种在非天然氨基酸化合物合成中关键中间体Wittig-Horner试剂的制备方法。
背景技术
肽是α-氨基酸以肽键连接在一起而形成的化合物,是蛋白质水解的中间产物。由两个氨基酸分子脱水缩合而成的化合物叫做二肽,同理类推还有三肽、四肽、五肽等。由三个或三个以上氨基酸分子组成的肽叫多肽。该类化合物由于在生理条件下,它们抗水解(酶解)裂解,以序列特异性方式识别互补核酸系列,并能够高亲和性地结合这些序列,所以多肽类化合物被视为生物科技和/或医疗应用中具有吸引力的化合物:目前多肽类化合物主要有天然多肽和合成多肽两种。
在合成多肽或拟肽化合物时,含多官能团的Wjttig-Horner试剂(甘氨酸衍生物)可作为多肽类化合物或拟肽类化合物合成的关键中间体,对多肽或拟肽合成具有重要的意义,如式(A)所示的化合物,是合成多种多肽或拟肽类药物的关键中间体。
发明内容
有鉴于此,本发明所要解决的技术问题在于提供了一种Wittig-Horner试剂的制备方法,本发明提供的Wi仕ig-Homer试剂的制备方法处理过程方便,且产物收率高。
与现有技术相比,本发明提供的Wittig-Homer试剂制备方法通过将式(I)结构的化合物与特定浓度的乙醛酸水溶液在甲苯中加热反应。结果发现,本发明在比较低的温度下原料可完全转化,且其得到的产品纯度高,直接过滤、打浆即可进行后续反应,进一步得到关键中间体式(III)结构的化合物,反应条件温和,且总收率高达80%以上,且第一步反应高达86%以上。
附图说明
图1为实施例得到的产物3的氢谱图;
图2为实施例得到的产物4的氢谱图;
图3为实施例得到的产物5的氢谱图;
图4为实施例得到的产物6的氢谱图。
具体实施方式
本发明提供了一种Wittig-Horner试剂的制备方法,包括:
1)将式(I)结构的化合物和乙醛酸水溶液混合反应,得到式(II)结构的化合物,
其中,所述R为C6~C20的芳基,C1~C8的烷基或C3~C7的环烷基,
所述乙醛酸水溶液中乙醛酸的质量浓度为40~70%;
所述反应的溶剂为甲苯;
2)将式(II)结构的化合物转化为式(III)结构的化合物,
其中,R1为C6~C20的芳基、C1~C8的烷基或C3~C7的环烷基。
按照本发明,本发明将式(I)结构的化合物和乙醛酸水溶液混合反应,得到式(II)结构的化合物;其中,式(I)结构的化合物中,所述R优选为苯基、萘基、蒽基、菲基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙烷基、环戊基或环己基;所述R1优选为苯基、萘基、蒽基、菲基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙烷基、环戊基或环己基。所述乙醛酸水溶液中乙醛酸的质量浓度优选为50~60%,更优选为50%~55%;所述式(I)结构的化合物与甲苯的用量比优选为1mmol:(4~6)mL,更优选为1mmol:(5~5.5)mL;所述反应的温度优选为40~45℃;所述式(I)结构的化合物与所述乙醛酸的摩尔比优选为1∶(1~3),更优选为1∶(2~3)。
按照本发明,本发明所述步骤2)具体为:
将式(II)结构的化合物转化成式(IV)结构的化合物,然后将式(IV)结构的化合物转化成式(III)结构的化合物;其中,本发明对转化的方法没有特殊要求,本领域技术人员可以根据实际情况选择合适的反应条件。
其中,所述R为C6~C20的芳基,C1~C8的烷基或C3~C7的环烷基。
更进一步的,本发明优选还将式(IV)结构的化合物转化为式(V)结构的化合物,然后将式(V)结构的化合物转化为式(III)结构的化合物;其中,本发明对转化的方法亦没有特殊要求,本领域技术人员可以根据实际需要选择合适的反应条件。
其中,所述R为C6~C20的芳基,C1~C8的烷基或C3~C7的环烷基。
本发明提供的制备方法通过将式(I)的化合物与特定浓度的乙醛酸水溶液在甲苯中反应,结果意外发现,本发明在比较低的温度就可以反应,且其得到的产品纯度高,直接打浆即可进入后续反应,进一步得到关键中间体化合物3,该制备方法反应条件温和,且收率高,适于实现工业化生产。
下面将结合本发明实施例的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
实施例1
反应流程
a)在250mL甲苯溶剂中,加入化合物1(150mmol,1.0eq)和质量浓度为50%的乙醛酸水溶液2(300mmol,2.0eq),反应液在45℃反应8小时,有大量白色不溶物生成,TLC检测发现化合物1反应完全,过滤不溶物即得粗式(粗产品纯度大于90%),在4℃下用200mL乙醚打浆纯化,得到产物3质量28.7g,产率86%。
对得到的产物的结构进行鉴定,结果见图1,图1为实施例得到的产物3的氢谱图。
b)在4℃下,化合物3(127.5mmol,1.0eq)溶于500mL甲醇中,缓慢加入浓硫酸25mmol,将反应液升温到室温反应过夜,会有部分产物析出,TLC检测原料3完全消失,即得产物4。
后处理:在35-37℃下浓缩去除大部分甲醇,将反应液缓慢倒入预冷到4℃的饱和碳酸氢钠水溶液中,使水溶液呈碱性,用乙酸乙酯萃取,硫酸镁干燥,浓缩。在浓缩物中加入乙醚充分搅拌,有白色固体析出,放置于4℃使产物充分析出,得到30.0g化合物4,产率为93%。
对得到的产物的结构进行鉴定,结果见图2,图2为实施例得到的产物4的氢谱图。
c)化合物4(118.6mmol,1.0eq)和三氯化磷(130.5mmol,1.1eq)溶于250mL甲苯,反应液在70℃反应12h,TLC检测发现化合物4消失,转化为极性比化合物4大的氯代产物。将反应液冷却到室温,缓慢加入亚磷酸三甲酯(130.5mmol,1.1eq),反应液在70℃反应4h,TLC检测氯代产物完全转化,得产物5。
后处理:在45-50℃下,旋蒸去除溶剂甲苯和易挥发物,将浓缩液缓慢倒入饱和碳酸氢钠中,用乙酸乙酯萃取,用硫酸镁干燥后浓缩。浓缩物中加入异丙醚搅拌,得35.3g白色固体化合物5,产率90%。
对得到的产物的结构进行鉴定,结果见图3,图3为实施例得到的产物5的氢谱图。
d)将化合物5(106.7mmol,1.0eq)溶于甲醇中(如有部分不溶可稍微加热助溶),加入BOC酸酐(117.4mmol,1.1eq)和质量5%的钯碳,在氢气下还原16h,TLC检测发现原料完全转化,过滤掉不溶物,浓缩得产物为无色油状物。在油状物中加入100mL异丙醚快速搅拌,得为化合物6为白色固体27.6g,产率87%。
对得到的产物的结构进行鉴定,结果见图4,图4为实施例得到的产物6的氢谱图。
对比例1
将实施例1步骤1中的反应溶剂甲苯换成乙醚,其它原料和反应条件不变,进行实验,化合物3的收率小于20%。
以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也落入本发明权利要求的保护范围内。
Claims (9)
2.根据权利要求1所述的制备方法,其特征在于,所述R为苯基、萘基、蒽基、菲基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙烷基、环戊基或环己基。
3.根据权利要求1所述的制备方法,其特征在于,所述R1为苯基、萘基、蒽基、菲基、甲基、乙基、正丙基、异丙基、正丁基、异丁基、叔丁基、正戊基、异戊基、正己基、环丙烷基、环戊基或环己基。
4.根据权利要求1所述的制备方法,其特征在于,所述乙醛酸水溶液中乙醛酸的质量浓度为50~60%。
5.根据权利要求1所述的制备方法,其特征在于,所述步骤1)中,所述式(I)结构的化合物与甲苯的用量比为lmmol∶(4~6)mL。
6.根据权利要求1所述的制备方法,其特征在于,所述步骤1)反应的温度为40~45℃。
7.根据权利要求1所述的制备方法,其特征在于,所述步骤1)中,所述式(I)结构的化合物与所述乙醛酸的摩尔比为1∶(1.1~1.3)。
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Non-Patent Citations (3)
Title |
---|
BERWE, MATHIAS等: ""Scalable synthesis of the desoxy-biphenomycin B core"", 《ORGANIC PROCESS RESEARCH & DEVELOPMENT》 * |
HORENSTEIN, BENJAMIN A等: ""Synthesis of unprotected (±)-tunichrome An-1, a tunicate blood pigment"", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
LIU, TAO等: ""Part 1. Synthesis of a potent histone deacetylase inhibitor. Part 2. Studies towards a stabilized helix-turn peptide"", 《DISS. ABSTR. INT., B 》 * |
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