CN108456227A - 一种1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯化合物及其合成方法和应用 - Google Patents
一种1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯化合物及其合成方法和应用 Download PDFInfo
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- 238000000034 method Methods 0.000 claims abstract description 16
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- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
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- PNFXCIIEGPPONE-UHFFFAOYSA-N CCC(CC)(C(C(OP(O)=O)(F)F)Cl)S(C(C=CC(C)=C1)C1=C1CCCC1)(=O)=O Chemical compound CCC(CC)(C(C(OP(O)=O)(F)F)Cl)S(C(C=CC(C)=C1)C1=C1CCCC1)(=O)=O PNFXCIIEGPPONE-UHFFFAOYSA-N 0.000 description 1
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
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Abstract
本发明公开了一种1,1‑二氟‑3‑磺酰基‑2‑氯‑3‑丁烯基膦酸酯类化合物,和采用光诱导的高位置选择性的磺酰基化反应合成方法,以及所述1,1‑二氟‑3‑磺酰基‑2‑氯‑3‑丁烯基膦酸酯类化合物作为酶抑制剂以及制备抗肿瘤药物中的应用。该化合物结构通式如下式(1)所示:其中:取代基R1,R2为烷基,或者R1R2相连形成C3‑C6环烷基,R3选自烷基、杂芳基和取代或未取代的芳基。相对于现有技术,本发明方法是一种绿色、高效、简单、高区域选择性合成1,1‑二氟‑3‑磺酰基‑2‑氯‑3‑丁烯基膦酸酯方法,该方法简便、条件温和、底物适用性好,区域选择性高,目标物的收率可达到45%‑84%,可见光诱导下选择性地在联烯2,3‑位双键上发生磺酰化反应。
Description
技术领域
本发明涉及一种1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物及其合成方法和应用,属于膦酸酯类化合物技术领域。
背景技术
砜类化合物有着独特的化学、生物和药物活性。砜骨架存在于多种天然产物中,它们在生物活性分子的合成中具有巨大的潜力,在医药、农药和材料化学中有着广泛的应用,因此C-S键的构建引起许多化学家的研究兴趣。另一方面磷酸酯是天然磷酸酯的活性基团,这类化合物在生物体内扮演着重要的角色,在细胞内代谢的调节和跨细胞膜信号传导中发挥十分重要的作用。但磷酸酯基团一般不用于在药物设计,这是由于磷酸酯易被磷酸酯酶水解,从而失去药效。因此寻找不易水解的磷酸酯模拟物和发掘新的酶抑制剂成为药物化学家们的研究热点。近年来,利用二氟亚甲基代替磷酸酯中的氧这一策略被人们所关注,如用来设计合成PTP抑制剂、神经鞘磷脂酶抑制剂等等。
虽然现有技术中已有含氟膦酸酯类化合物的研究,但是也存在生物活性不够理想,制备工艺复杂和区域选择性差等缺陷。
发明内容
发明目的:针对上述技术问题,本发明目的提供一种1,1-二氟3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物及其合成方法和应用。
技术方案:本发明公开了一种1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其结构通式如下式(1)所示:
其中:取代基R1,R2为烷基,或者R1R2相连形成C3-C6环烷基,R3选自烷基、杂芳基和取代或未取代的芳基。所述R1R2相连形成C3-C6环烷基,其中,C原子的数量包括R1和R2中间的C原子,例如R1R2相连形成C5环烷基时,化合物结构如下所示:
优选,所述的取代基R1为C1-C5的烷基,R2为C1-C5的烷基,或者R1R2相连形成C3-C6环烷基;R3为C3-C7链状烷基、C3-C6环烷基、萘基、苯基或邻、间、对取代的苯基、或为含N、O或S的五~十元环的杂芳基。
优选,所述的取代基R1,R2选自甲基,或者R1R2相连形成环戊基;R3选自丁烷基、环丙基、苯基、4-甲基苯基、4-三氟甲基苯基、萘基和2-噻吩基。
本发明还提供了所述1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物的合成方法,包括以下步骤:以化合物(2)α,α-二氟亚甲基-β-联烯膦酸酯为原料,加入磺酰氯化合物(3),在铱催化剂和蓝色可见光照射下发生磺酰化反应,制得所述1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其反应过程如下所示:
其中,化合物(2)中,取代基R1,R2为烷基,或者R1R2相连形成C3-C6环烷基;化合物(3)中,R3选自烷基、杂芳基和取代或未取代的芳基
其中化合物(2)α,α-二氟亚甲基-β-联烯膦酸酯的制备可参见文献。
所述铱催化剂为三价铱,优选fac-Ir(ppy)3。
所述α,α-二氟亚甲基-β-联烯膦酸酯与磺酰氯化合物的摩尔比为1:(1~3)。
所述铱催化剂与α,α-二氟亚甲基-β-联烯膦酸酯的摩尔比为(0.02~0.1):1,优选0.05:1。
所述磺酰化反应在惰性气体气氛中进行。
本发明方法合成的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物可进一步采用柱层析的方法纯化。
本发明最后还提供了所述1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物作为酶抑制剂以及制备抗肿瘤药物中的应用。
由于砜类化合物和含氟膦酸酯类化合物都具有生物活性,分子中不仅具有磺酰基而且具有二氟亚甲基膦酸酯的结构单元,使1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物具有更多样的生物活性,如酶抑制活性,以及更进一步的抗肿瘤活性。利用本发明方法合成的具有磺酰基的含氟膦酸酯有望成为一类重要的生物活性化合物。
本发明首先考虑到相对于其它分子间的磺酰化反应,磺酰氯作为磺酰基的提供者更简单易得,α,α-二氟亚甲基-β-联烯膦酸酯的可见光诱导的磺酰化反应更具有意义,并且此发明有着良好的选择性以及较高的产率,因此考察了fac-Ir(ppy)3催化,蓝光照射下磺酰氯与α,α-二氟亚甲基-β-联烯膦酸酯磺酰化反应。
本发明紧密围绕上述科学问题,通fac-Ir(ppy)3催化,可见光诱导含氟联烯的磺酰化反应高选择性合成一系列新型磷酸酯模拟物—1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯。
技术效果
相对于现有技术,本发明1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物具备多种的酶抑制活性以及抗肿瘤活性,并且合成方法是一种高效、简单、高区域选择性合成方法,该方法绿色简便、条件温和、产率优良,区域选择性高,磺酰化反应选择性地在联烯2,3位双键上发生。
具体实施方式
下面通过具体实施例对本发明所述的技术方案给予进一步详细的说明,但有必要指出以下实施例只用于对发明内容的描述,并不构成对本发明保护范围的限制。
根据本发明的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯的合成方法,以具有上述式(2)结构的联烯与磺酰氯在催化剂fac-Ir(ppy)3,可见光诱导下发生磺酰化反应,生成1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯。所述方法通常在惰性气体气氛中进行,如在N2或Ar气保护下,在反应瓶中加入联烯膦酸酯、金属铱催化(fac-Ir(ppy)3)、磺酰氯和溶剂(如乙腈),通常联烯膦酸酯与fac-Ir(ppy)3催化剂、磺酰氯摩尔比为1:0.05:3,反应室温蓝光照射下,薄层色谱(Thin Layer Chromatography,TLC)跟踪反应;反应结束后加溶剂稀释,洗涤,干燥,过滤,旋转蒸发除去溶剂后得粗品1,1-二氟3-磺酰基-2-氯-3-丁烯基膦酸酯,粗品可采用柱层析的方法精制得纯品。如采用柱层析,可用硅胶作为固定相,所采用的展开剂为非极性溶剂和极性溶剂的混合溶剂,如石油醚-乙酸乙酯,正己烷-乙酸乙酯,二氯甲烷-乙酸乙酯等混合溶剂。其体积比为非极性溶剂和极性(2-3.5):1,如:石油醚:乙酸乙酯=3:1。
实施例1:
Ar或N2保护下,在反应管中依次加入联烯(0.4mmol),苯磺酰氯(1.2mmol),fac-Ir(ppy)3(5%mmol),乙腈4mL,常温,5W蓝光照射下反应,TLC监测至反应结束,加入水淬灭,乙酸乙酯萃取,合并有机相,饱和食盐水洗涤,无水硫酸钠干燥,过滤浓缩,以二氯甲烷-乙酸乙酯为淋洗剂柱层析分离得到产物。反应
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率84%。
(2-chloro-1,1-difluoro-4-methyl-3-(phenylsulfonyl)pent-3-en-1-yl)phosphonate IR(neat):2984,2922,1612,1450,1304,1150,1080,1033,895,834,756,717,687,602cm-1;1H-NMR(400MHz,CDCl3):δ7.87-7.85(m,2H),7.58-7.49(m,3H),6.24(dd,JH-F=20.2,11.4Hz,1H),4.35-4.30(m,4H),2.17(s,3H),2.01(s,3H),1.39(t,J=7.0Hz,6H);13C-NMR(100MHz,CDCl3):δ162.5,142.2,133.0,131.0(t,JC-F=3.3Hz),128.9,126.6,117.3(ddd,JC-F=271.0Hz,JC-F=266.7Hz,JC-P=213.0Hz),65.1(d,JC-P=6.7Hz),65.0(d,JC-P=6.8Hz),52.5(td,JC-F=25.4Hz,JC-P=22.4Hz),25.9(t,JC-F=6.4Hz),24.9,16.2(d,JC-P=5.0Hz,),16.1(d,JC-P=5.4Hz);19F-NMR(376MHz,CDCl3):δ-104.6to-105.6(m,1F),-108.3to-109.4(m,1F);31P-NMR(162MHz,CDCl3):δ5.29-3.82(m);HRMS(DART)Calcd forC16H23O5ClF2PS[M+H]+requires 431.0655,Found:431.0648.
实施例2:
所得到的3-磺酰基-2-氯二氟亚甲基烯丙基膦酸酯其结构如下式,收率83%。
Diethyl(2-chloro-1,1-difluoro-4-methyl-3-((4-(trifluoromethyl)phenyl)sulfonyl)pent-3-en-1-yl)phosphonate
IR(neat):3064,2983,2925,1617,1453,1371,1306,1151,1085,1036,889,831,758,692,603cm-1;1H-NMR(400MHz,CDCl3):δ8.01(d,J=8.0Hz,2H),7.78(d,J=8.0Hz,2H),6.19(dd,JH-F=19.4,11.8Hz,1H),4.34-4.29(m,4H),2.20(s,3H),2.03(s,3H),1.39(t,J=7.0Hz,6H);13C-NMR(100MHz,CDCl3):δ164.0,146.0,134.6(q,JC-F=33.1Hz),130.7,127.4,126.2(q,JC-F=3.6Hz),123.0(q,JC-F=271.3Hz),117.3(ddd,JC-F=271.4Hz,JC-F=266.4Hz,JC-P=212.9Hz),65.2(d,JC-P=6.6Hz),65.1(d,JC-P=6.8Hz),52.7(td,JC-F=JC-P=24.5Hz),26.1(t,JC-F=5.7Hz),25.1,16.2(d,JC-P=5.0Hz),16.2(d,JC-P=5.0Hz);19F-NMR(376MHz,CDCl3):δ-63.2(s,3F),-105.0to-106.1(m,1F),-107.9to-109.0(m,1F);31P-NMR(162MHz,CDCl3)δ:5.09-3.72(m);HRMS(DART)Calcd for C17H22O5ClF5PS[M+H]+requires499.0529,Found:499.0528.
实施例3:
操作同前,反应过程如下:
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率70%。
Diethyl(2-chloro-3-cyclopentylidene-1,1-difluoro-3-tosylpropyl)phosphonate IR(neat):2984,2930,1720,1604,1450,1288,1141,1018,887,810,656cm-1;1H-NMR(400MHz,CDCl3):δ7.74(d,J=8.4Hz,2H),7.29(d,J=8.0Hz,2H),6.09(ddd,JH-F=20.6,10.4Hz,JH-P=1.4Hz,1H),4.36-4.26(m,4H),3.04-2.90(m,2H),2.63-2.55(m,1H),2.40(s,3H),2.27-2.18(m,1H),1.76-1.69(m,1H),1.66-1.55(m,2H),1.51-1.44(m,1H),1.38(t,J=7.2Hz,6H);13C-NMR(100MHz,CDCl3):δ173.4,144.0,138.4,129.5,127.3,117.5(td,JC-F=271.2Hz,JC-F=266.1Hz,JC-P=212.8Hz),65.1(d,JC-P=6.6Hz),65.0(d,JC-P=6.9Hz),53.5(td,JC-F=25.6Hz,JC-P=22.0Hz),36.1(t,JC-P=5.8Hz),35.3,25.9,25.7,21.5,16.3(d,JC-P=5.3Hz),16.2(d,JC-P=4.4Hz);19F-NMR(376MHz,CDCl3)δ:-104.2to-105.3(m,1F),-108.4to-109.2(m,1F);31P-NMR(162MHz,CDCl3):δ5.31-3.94(m);HRMS(DART)Calcd for C19H27O5ClF2PS[M+H]+requires 471.0968,Found:471.0967.
实施例4:
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率70%。
Diethyl(2-chloro-1,1-difluoro-4-methyl-3-(naphthalen-1-ylsulfonyl)pent-3-en-1-yl)phosphonate
IR(neat);3054,2992,2922,1612,1450,1380,1311,1265,1141,1033,895,825,748,656cm-1;1H-NMR(400MHz,CDCl3):δ8.49(s,1H),7.99-7.90(m,3H),7.80(d,J=8.8Hz,1H),7.68-7.60(m,2H),6.19(dd,JH-F=19.8,11.0Hz,1H),4.38-4.30(m,4H),2.19(s,3H),2.07(s,3H),1.42(t,J=8.2Hz,6H);13C-NMR(100MHz,CDCl3):δ162.8,150.9,,131.9,131.3(dd,JC-F=JC-P=3.6Hz),129.5,129.4,129.1,128.4,128.0,127.7,121.9,1154(ddd,JC-F=271.5Hz,JC-F=266.1Hz,JC-P=213.2Hz),65.3(d,JC-P=6.7Hz,),65.2(d,JC-P=6.8Hz),52.7(td,JC-F=25.3Hz,JC-P=22.4Hz),26.2(t,JC-F=6.4Hz),25.1,16.4(d,JC-P=4.5Hz),16.3(d,JC-P=5.1Hz);19F-NMR(376MHz,CDCl3):δ-104.5to-105.6(m,1F),-108.1to-109.2(m,1F);31P-NMR(162MHz,CDCl3):δ5.30-3.92(m);HRMS(DART)Calcd for C20H25O5ClF2PS[M+H]+requires 481.0811,Found 481.0810.
实施例5:
操作同前,反应过程如下:
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率57%。
Diethyl(2-chloro-1,1-difluoro-4-methyl-3-(thiophen-2-ylsulfonyl)pent-3-en-1-yl)p hosphonate
IR(neat):3103,2990,2926,1607,1442,1403,1309,1277,1143,1089,1018,837,735,664,610cm-1;1H-NMR(400MHz,CDCl3):δ7.67(dd,J=3.8,1.4Hz,1H),7.65(dd,J=5.0,1.4Hz,1H),7.09(dd,J=5.0,3.8Hz,1H),6.16(ddd,JH-F=21.6,9.6Hz,JH-P=2.0Hz,1H),4.35-4.29(m,4H),2.24(s,3H),2.21(t,J=2.0Hz,3H),1.39(t,J=7.0Hz,6H);13C-NMR(100MHz,CDCl3)δ:163.1,143.5,133.0,131.8(dd,JC-F=5.4,2.0Hz),127.2,117.3(ddd,JC-F=270.7,265.3Hz,JC-P=212.9Hz),65.2(d,JC-P=6.7Hz),65.0(d,JC-P=6.8Hz),52.5(ddd,JC-F=27.0Hz,JC-F=24.3Hz,JC-P=21.9Hz),26.3(dd,JC-F=7.9,4.9Hz),25.1,16.2(d,JC-P=3.7Hz),16.1(d,JC-P=3.7Hz);19F-NMR(376MHz,CDCl3):δ-103.6to-104.7(m,1F),-109.6to-110.8(m,1F);31P-NMR(162MHz,CDCl3):δ5.23-3.86(m);HRMS(DART)Calcdfor C14H21O5ClF2PS2[M+H]+requires 437.0219,Found:437.0216.
实施例6:
操作同前,反应过程如下:
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率45%。
Diethyl(2-chloro-3-(cyclopropylsulfonyl)-1,1-difluoro-4-methylpent-3-en-1-yl)phosphonate.
IR(neat):2984,2930,1620,1442,1373,1288,1126,1095,1033,895,834,735cm-1;1H-NMR(400MHz,CDCl3)δ:5.81(ddd,JH-F=21.3,10.3Hz,JH-P=1.9Hz,1H),4.29-4.17(m,4H),2.58-2,52(m,1H),2.34(s,3H),2.18(s,3H),1.31(t,J=7.0Hz,7H),1.12-1.06(m,1H),1.02-0.92(m,2H);13C-NMR(100MHz,CDCl3)δ:161.1,131.3,117.2(ddd,JC-F=272.1,265.5Hz,JC-P=213.1Hz),65.0(d,JC-P=7.3Hz),64.9(d,JC-P=7.4Hz),52.5(td,JC-F=JC-P=24.2Hz),32.9,25.7(dd,JC-F=7.6,5.2Hz),25.2,16.1(d,JC-P=4.6Hz),16.0(d,JC-P=4.9Hz),5.5,5.3;19F-NMR(376MHz,CDCl3):δ-104.1to-105.2(m,1F),-109.2to-110.3(m,1F);31P-NMR(162MHz,CDCl3):δ5.24-3.82(m);HRMS(DART)Calcd.for C13H23O5ClF2PS[M+H]+requires 395.0655,Found:395.0650.
实施例7:
操作同前,反应过程如下:
所得到的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯其结构如下式,收率31%。
Diethyl(3-(butylsulfonyl)-2-chloro-1,1-difluoro-4-methylpent-3-en-1-yl)phosphonate IR(neat):2968,2930,2877,1612,1453,1277,1171,1125,1102,1034,889,836,798cm-1;1H-NMR(400MHz,CDCl3):δ5.91(ddd,JH-F=21.2Hz,JH-F=10.4Hz,JH-P=1.6Hz,1H),4.31-4.22(m,4H),3.07-3.02(m,2H),2.32(s,3H),2.22(t,J=2.0Hz,3H),1.77-1.67(m,2H),1.46-1.39(m,2H),1.35(t,J=7.2Hz,6H),0.9(t,J=7.2Hz,3H);13C-NMR(100MHz,CDCl3):δ162.0,130.3(d,JC-F=3.5Hz),128.2,124.3,117.4(ddd,JC-F=272.3Hz,JC-F=265.6 Hz,JC-P=213.2 Hz),65.2(d,JC-P=7.3 Hz),65.1(d,JC-P=7.4 Hz),55.4,52.5(td,JC-F=JC-P=24.3 Hz),25.9(t,JC-P=6.2Hz),25.3,23.7,21.6,16.3(d,JC-P=5.0Hz),16.1(d,JC-P=5.1 Hz),13.5;19F-NMR(376 MHz,CDCl3):δ-104.2 to-105.3(m,1F),-109.3 to-110.4(m,1F);31P-NMR(162 MHz,CDCl3):δ5.05-3.67(m);HRMS(DART)Calcd.ForC14H27O5ClF2PS[M+H]+requires 411.0968,Found:411.0967。
Claims (9)
1.一种1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其结构通式如下式(1)所示:
其中:取代基R1,R2为烷基,或者R1R2相连形成C3-C6环烷基,R3选自烷基、杂芳基和取代或未取代的芳基。
2.根据权利要求1所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其特征在于,所述的取代基R1为C1-C5的烷基,R2为C1-C5的烷基,或者R1R2相连形成C3-C6环烷基;R3为C3-C7链状烷基、C3-C6环烷基、萘基、苯基或邻、间、对取代的苯基、或为含N、O或S的五~十元环的杂芳基。
3.根据权利要求1所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其特征在于,所述的取代基R1,R2选自甲基,或者R1R2相连形成环戊基;R3选自丁烷基、环丙基、苯基、4-甲基苯基、4-三氟甲基苯基、萘基和2-噻吩基。
4.权利要求1-3任一项所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物的合成方法,其特征在于,包括以下步骤:以化合物(2)α,α-二氟亚甲基-β-联烯膦酸酯为原料,加入磺酰氯化合物(3),在铱催化剂和蓝色可见光照射下发生磺酰化反应,制得所述1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物,其反应过程如下所示:
其中,化合物(2)中,取代基R1,R2为烷基,或者R1R2相连形成C3-C6环烷基;化合物(3)中,R3选自烷基、杂芳基和取代或未取代的芳基。
5.根据权利要求4所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物的合成方法,其特征在于,所述铱催化剂为三价铱。
6.根据权利要求4所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物的合成方法,其特征在于,所述α,α-二氟亚甲基-β-联烯膦酸酯与磺酰氯化合物的摩尔比为1:(1~3)。
7.根据权利要求4所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物的合成方法,其特征在于,所述铱催化剂与α,α-二氟亚甲基-β-联烯膦酸酯的摩尔比为(0.02~0.1):1,优选0.05:1。
8.根据权利要求4所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯的合成方法,其特征在于,所述磺酰化反应在惰性气体气氛中进行。
9.权利要求1-3任一项所述的1,1-二氟-3-磺酰基-2-氯-3-丁烯基膦酸酯类化合物作为酶抑制剂以及制备抗肿瘤药物中的应用。
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CN108383872A (zh) * | 2018-04-18 | 2018-08-10 | 南京师范大学 | 一种-1,1-二氟-3-磺酰基-2,4-戊二烯膦酸酯类化合物及其合成方法和应用 |
CN109503658A (zh) * | 2019-01-03 | 2019-03-22 | 南京师范大学 | 一种(e)-3-芳基-1-氟-1,3-丁二烯膦酸酯类化合物及其合成方法和应用 |
CN112552342A (zh) * | 2020-12-07 | 2021-03-26 | 新乡医学院 | 一类包含二氟烷基的四取代烯基氧化膦化合物及其制备方法 |
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