含稠杂环结构的化合物及其制备方法和应用以及杀菌剂转让专利
申请号 : CN202010760478.X
文献号 : CN111848612B
文献日 : 2021-09-14
发明人 : 杨光富 , 李建龙 , 周立明
申请人 : 华中师范大学
摘要 :
权利要求 :
1.一种式(1)所示结构的含稠杂环结构的化合物或其农业化学上可接受的盐,在式(1)中,
R选自‑CHO、‑CH2OH、‑CH(OH)CH3、‑CH2CH2OH、‑CH2OCH3、‑CH(CH3)OCH3、‑CH2CH2OCH3、‑CH=NOH、‑CH=NOCH3、‑CH2NHCH3、‑CH2N(CH3)2、 ‑CH3、‑CH2Cl、‑CHClCH3、‑CH2CH2Cl、‑CH2F、‑CHF2、‑CF3、‑CHFCH3、‑CH2CH2F、‑CHFCH2F、‑CF2CH3、‑CH2CHF2、‑CH2CF3、‑CF2CF3、‑CH2CH2CH3、‑C(CH3)3、‑COCH3、‑CH2COCH3、‑COCH2CH3、‑CH=CH2、‑CH=CF2、‑CH=CHCH3、‑C≡CH、‑C≡C‑I、‑C≡CCH3、‑OCH3、‑OH、‑NO2、‑NH2、‑NHCH3、‑N(CH3)2、‑N(CH2CH3)CH3、‑NHOH、‑NHOCH3、‑C≡N、‑Br或‑H;
R1、R2和R3均为H;
R4为2,6‑二氟苯基或2‑氯‑6‑[(甲基磺酰基)氧基]苯基。
2.权利要求1所述的含稠杂环结构的化合物或其农业化学上可接受的盐在防治植物卵菌病害中的应用。
3.根据权利要求2所述的应用,其中,所述植物卵菌病害选自致病疫霉、大豆疫霉、辣椒疫霉、荔枝霜疫霉和黄瓜霜霉病菌中的至少一种病菌导致的病害。
4.权利要求1所述的含稠杂环结构的化合物或其农业化学上可接受的盐作为农药杀菌剂的应用。
5.一种杀菌剂,该杀菌剂由活性成分和辅料组成,所述活性成分包括权利要求1所述的式(1)所示结构的含稠杂环结构的化合物或其农业化学上可接受的盐中的至少一种。
6.根据权利要求5所述的杀菌剂,其中,所述活性成分的含量为1‑99.9重量%。
7.根据权利要求6所述的杀菌剂,其中,该杀菌剂的剂型选自乳油、悬浮剂、粉剂、粒剂、水剂、毒饵、母液和母粉中的至少一种。
8.根据权利要求7所述的杀菌剂,其中,该杀菌剂的剂型为可湿性粉剂。
说明书 :
含稠杂环结构的化合物及其制备方法和应用以及杀菌剂
技术领域
为农药杀菌剂的应用以及一种杀菌剂。
背景技术
等。同时,其引起的病害也较难防治,因此给农业生产带来极大的损失。
历史上著名的爱尔兰大饥馑的发生。其它植物病原菌也能导致病害的严重发生,例如辣椒
疫霉容易引起辣椒、番茄、茄子和瓜类等作物的疫病,黄瓜霜霉病菌引起的瓜果类霜霉病
等。
着这些杀菌剂使用时间的延长和长期的不合理使用,使得很多病原菌出现了严重的抗药
性。
发明内容
氨基烷基、C3‑C8环烷氨基烷基、C2‑C4烷基羰基、醛基、醛肟基、硝基、氨基、氰基、氟、溴、C2‑C6
醛肟醚基、C2‑C6含氧环烷基、C3‑C6环烷基、C4‑C10环烷基烷基、C4‑C10烷基环烷基、C5‑C10烷基
环烷基烷基、C3‑C6卤代环烷基、羟基、C1‑C4烷氧基、C1‑C4卤代烷氧基、C1‑C4烷硫基、C1‑C4烷
基亚磺酰基、C1‑C4烷基磺酰基、C1‑C4卤代烷硫基、C1‑C4卤代烷基亚磺酰基、C1‑C4卤代烷基磺
酰基、C1‑C4烷基氨基、C2‑C8二烷基氨基、C3‑C6环烷基氨基、C2‑C4烷基羰基氨基、羟胺基、C1‑
C4烷氧氨基、C2‑C4卤代烷基羰基氨基、C2‑C4烷基羰基、C2‑C6烷氧羰基、C2‑C6烷基羰氧基、C2‑
C6烷基羰硫基、C2‑C6烷基氨基羰基、C3‑C8二烷基氨基羰基或C3‑C6三烷基甲硅烷基;
烷基氨基烷基、C3‑C8环烷氨基烷基、C2‑C4烷基羰基、醛基、醛肟基、硝基、氨基、氰基、卤素、
C2‑C6醛肟醚基、C2‑C6含氧环烷基、C3‑C6环烷基、C4‑C10环烷基烷基、C4‑C10烷基环烷基、C5‑C10
烷基环烷基烷基、C3‑C6卤代环烷基、羟基、C1‑C4烷氧基、C1‑C4卤代烷氧基、C1‑C4烷硫基、C1‑
C4烷基亚磺酰基、C1‑C4烷基磺酰基、C1‑C4卤代烷硫基、C1‑C4卤代烷基亚磺酰基、C1‑C4卤代烷
基磺酰基、C1‑C4烷基氨基、C2‑C8二烷基氨基、C3‑C6环烷基氨基、C2‑C4烷基羰基氨基、羟胺基、
C1‑C4烷氧氨基、C2‑C4卤代烷基羰基氨基、C2‑C4烷基羰基、C2‑C6烷氧羰基、C2‑C6烷基羰氧基、
C2‑C6烷基羰硫基、C2‑C6烷基氨基羰基、C3‑C8二烷基氨基羰基和C3‑C6三烷基甲硅烷基;
异戊基、正己基等。“C1‑C6卤代烷基”的定义与“C4‑C6烷基”的定义相似,不同的是,“C1‑C6卤
代烷基”上的至少一个H被卤素原子取代,且碳原子总数不同,例如可以有1、2、3、4、5或6个H
由选自氟、氯、溴、碘的至少一种卤素原子取代,且该C1‑C6卤代烷基的碳原子总数为1‑6。
“C1‑C4羟基烷基”的定义与“C4‑C6烷基”的定义相似,不同的是,“C1‑C4羟基烷基”上的至少一
个H被羟基取代,例如可以有1、2或3个H由羟基取代,且该C1‑C4羟基烷基的碳原子总数为1‑
4。“C2‑C4烷氧基烷基”的定义与“C4‑C6烷基”的定义相似,不同的是,“C2‑C4烷氧基烷基”上的
至少一个H被烷氧基取代,例如可以有1、2或3个H由烷氧基取代,且该C2‑C4烷氧基烷基的碳
1 2 1
原子总数为2‑4,该C2‑C4烷氧基烷基例如可以表示为R O‑R ‑,其中,RO即为该C2‑C4烷氧基
2
烷基中的烷氧基,R即为该C2‑C4烷氧基烷基中的烷基。
个H被卤素原子取代,例如可以有1、2、3、4、5或6个H由选自氟、氯、溴、碘的至少一种卤素原
子取代。
个H被卤素原子取代,例如可以有1、2、3、4、5或6个H由选自氟、氯、溴、碘的至少一种卤素原
子取代。
以表示为R‑NH‑R‑,且R和R的碳原子总数为2‑6。“C3‑C6二烷基氨基烷基”的定义与“C2‑C6
5 6 7 5
烷基氨基烷基”的定义相似,该C3‑C6二烷基氨基烷基例如可以表示为R‑N(R)‑R ‑,且R 、
6 7
R、R的碳原子总数为3‑6。
以表示为R‑R‑,其中,R为含有N原子的环基,以及该R中的N原子与R直接连接。
R ‑CO‑,R 即为C2‑C4烷基羰基中的烷基。
R ‑ON=CH‑,该R 表示烷基。
C6环烷基”的成环原子均为C原子,且该基团的碳原子总数为3‑6。“C4‑C10环烷基烷基”的定
义与“C2‑C6含氧环烷基”的定义类似,但“C4‑C10环烷基烷基”的成环原子均为C原子,该基团
12 13 12
的碳原子总数为4‑10,该“C4‑C10环烷基烷基”例如可以表示为R ‑R ‑,其中,R 为环烷基,
13
R 为连接环烷基和式(1)所示结构的化合物中的母核结构基团。“C4‑C10烷基环烷基”的定义
14 15 15
与“C4‑C10环烷基烷基”的定义类似,该C4‑C10烷基环烷基例如可以表示为R ‑R ‑,其中,R
14 15
为环烷基,且R 为取代该R 中的H的烷基。
R ‑R ‑R ‑,其中,R 为环烷基,该环烷基连接作为烷基的R 和R ,且R 直接与式(1)所示
结构的化合物中的母核结构连接。
基氨基烷基、C3‑C8环烷氨基烷基、C2‑C6烷基氨基、C3‑C6二烷基氨基、羟胺基、C1‑C4烷氧胺基、
C1‑C4烷氧基、C2‑C4烷基羰基、C1‑C4烷基磺酰基、醛基、C1‑C4醛肟基、羟基、硝基、氨基、氰基、
卤素、C2‑C6醛肟醚基、1,3‑二氧环戊基;
烷氧基烷基、C2‑C6烷基氨基烷基、C3‑C6二烷基氨基烷基、C3‑C8环烷氨基烷基、C2‑C6烷基氨
基、C3‑C6二烷基氨基、羟胺基、C1‑C4烷氧胺基、C1‑C4烷氧基、C2‑C4烷基羰基、C1‑C4烷基磺酰
基、醛基、醛肟基、羟基、硝基、氨基、氰基、氟、氯、溴、碘、C2‑C6醛肟醚基和1,3‑二氧环戊基;
2‑氯乙基、1‑氟乙基、2‑氟乙基、1,1‑二氟乙基、2,2‑二氟乙基、1,2‑二氟乙基、2,2,2‑三氟
乙基、1,1,2,2,2‑五氟乙基、乙酰基甲基、1‑氯‑乙烯基、2‑氯‑乙烯基、2,2‑二氯乙烯基、1,
2‑二氯乙烯基、1‑氟‑乙烯基、2‑氟‑乙烯基、2,2‑二氟乙烯基、1,2‑二氟乙烯基、氟代乙炔
基、氯代乙炔基、碘代乙炔基、羟基甲基、1‑羟基乙基、2‑羟基乙基、羟基正丙基、甲氧基甲
基、1‑甲氧基乙基、2‑甲氧基乙基、3‑甲氧基正丙基、乙氧基甲基、1‑乙氧基乙基、2‑乙氧基
乙基、3‑乙氧基正丙基、甲基氨基甲基、1‑甲基氨基乙基、2‑甲基氨基乙基、甲基氨基正丙
基、二甲基氨基甲基、1‑二甲基氨基乙基、2‑二甲基氨基乙基、二甲基氨基正丙基、
甲氨基、二甲氨基、甲基乙基氨基、羟胺基、甲氧胺基、甲氧基、乙氧
基、乙酰基、丙酰基、甲基磺酰基、醛基、‑CH=NOH、‑CH=NOCH3、羟基、硝基、氨基、氰基、氟、
溴或1,3‑二氧环戊基;
基、氟甲基、二氟甲基、三氟甲基、1‑氯乙基、2‑氯乙基、1‑氟乙基、2‑氟乙基、1,1‑二氟乙基、
2,2‑二氟乙基、1,2‑二氟乙基、2,2,2‑三氟乙基、1,1,2,2,2‑五氟乙基、乙酰基甲基、1‑氯‑
乙烯基、2‑氯‑乙烯基、2,2‑二氯乙烯基、1,2‑二氯乙烯基、1‑氟‑乙烯基、2‑氟‑乙烯基、2,2‑
二氟乙烯基、1,2‑二氟乙烯基、氟代乙炔基、氯代乙炔基、碘代乙炔基、羟基甲基、1‑羟基乙
基、2‑羟基乙基、羟基正丙基、甲氧基甲基、1‑甲氧基乙基、2‑甲氧基乙基、3‑甲氧基正丙基、
乙氧基甲基、1‑乙氧基乙基、2‑乙氧基乙基、3‑乙氧基正丙基、甲基氨基甲基、1‑甲基氨基乙
基、2‑甲基氨基乙基、甲基氨基正丙基、二甲基氨基甲基、1‑二甲基氨基乙基、2‑二甲基氨基
乙基、二甲基氨基正丙基、 甲氨基、二甲氨基、甲基乙基氨基、羟胺
基、甲氧胺基、甲氧基、乙氧基、乙酰基、丙酰基、甲基磺酰基、醛基、‑CH=NOH、‑CH=NOCH3、
羟基、硝基、氨基、氰基、氟、氯、溴、碘和1,3‑二氧环戊基;
CHClCH3、‑CH2CH2Cl、‑CH2F、‑CHF2、‑CF3、‑CHFCH3、‑CH2CH2F、‑CHFCH2F、‑CF2CH3、‑CH2CHF2、‑
CH2CF3、‑CF2CF3、‑CH2CH2CH3、‑C(CH3)3、‑COCH3、‑CH2COCH3、‑COCH2CH3、‑CH=CH2、‑CH=CF2、‑
CH=CHCH3、‑C≡CH、‑C≡C‑I、‑C≡CCH3、‑OCH3、‑OH、‑NO2、‑NH2、‑NHCH3、‑N(CH3)2、‑N(CH2CH3)
CH3、‑NHOH、‑NHOCH3、‑C≡N、‑Br或‑H;
CHClCH3、‑CH2CH2Cl、‑CH2F、‑CHF2、‑CF3、‑CHFCH3、‑CH2CH2F、‑CHFCH2F、‑CF2CH3、‑CH2CHF2、‑
CH2CF3、‑CF2CF3、‑CH2CH2CH3、‑C(CH3)3、‑COCH3、‑CH2COCH3、‑COCH2CH3、‑CH=CH2、‑CH=CF2、‑
CH=CHCH3、‑C≡CH、‑C≡C‑I、‑C≡CCH3、‑OCH3、‑OH、‑NO2、‑NH2、‑NHCH3、‑N(CH3)2、‑N(CH2CH3)
CH3、‑NHOH、‑NHOCH3、‑C≡N、‑Br或‑H;
CHClCH3、‑CH2CH2Cl、‑CH2F、‑CHF2、‑CF3、‑CHFCH3、‑CH2CH2F、‑CHFCH2F、‑CF2CH3、‑CH2CHF2、‑
CH2CF3、‑CF2CF3、‑CH2CH2CH3、‑C(CH3)3、‑COCH3、‑CH2COCH3、‑COCH2CH3、‑CH=CH2、‑CH=CF2、‑
CH=CHCH3、‑C≡CH、‑C≡C‑I、‑C≡CCH3、‑OCH3、‑OH、‑NO2、‑NH2、‑NHCH3、‑N(CH3)2、‑N(CH2CH3)
CH3、‑NHOH、‑NHOCH3、‑C≡N、‑Br或‑H;
方法。
选情况下,所述碱性试剂为氢化钠、碳酸钾和碳酸铯中的至少一种。
示的化合物的方法,本领域技术人员不应理解为对本发明的限制。
洗涤、旋转蒸发、柱层析、重结晶等,本发明对此没有特别的限制,只要能够获得本发明前述
含稠杂环结构的化合物即可。
的盐、水合物和溶剂化物中的至少一种。
治药剂烯酰吗啉,具有很好的市场开发前景。
具体实施方式
个范围的端点值和单独的点值之间,以及单独的点值之间可以彼此组合而得到一个或多个
新的数值范围,这些数值范围应被视为在本文中具体公开。
物的粗品,并且以1‑氯丁烷洗涤,过滤,收集滤饼;并且将滤液重结晶,过滤,滤饼干燥后也
获得式(2‑4)所示的化合物,合并两批后得到式(2‑4)所示的化合物的纯品。
溶剂,得到式(2‑5)所示的化合物,直接用于下一步反应。
完毕,除去丙酮,加入2L水,以500mL*3乙酸乙酯萃取,合并有机相,干燥浓缩后得到式(2‑6)
所示的化合物的粗品,进一步以硅胶与石油醚和乙酸乙酯形成的洗脱体系进行柱层析纯
化,最终得到式(2‑6)所示的化合物纯品;
500mL*5的乙酸乙酯萃取,合并有机相,干燥浓缩后得到式(2‑7)所示的化合物。
续保持温度在‑5~0℃,滴加完毕,升温至室温,反应完毕,分液除去水相,有机相以饱和食
盐水洗涤,无水硫酸钠干燥,并且减压浓缩后,得到式(2‑1)所示的化合物粗品,然后加入乙
酸乙酯,搅拌成均匀的浆液后过滤,滤饼干燥后,得到式(2‑1)所示的化合物纯品。
入饱和氯化铵淬灭,以乙酸乙酯萃取,有机相经干燥、浓缩后得到3‑氯‑2‑(1‑羟基乙基)‑苯
酚粗品,直接用于下一步反应;
机相以饱和碳酸氢钠洗涤,经过干燥浓缩后得到化合物3‑氯‑2‑乙烯基‑苯酚;
完毕后,继续搅拌反应30min,反应完毕,加入250mL 1N稀盐酸,并且以乙酸乙酯萃取,有机
相经过干燥、过滤和柱层析纯化后得到式(2‑8)所示的化合物。
液中的溶剂,得到式(2‑9)所示的化合物,直接用于下一步反应。
完毕,除去丙酮,加入2L水,以500mL*3乙酸乙酯萃取,合并有机相,干燥浓缩后得到式(2‑
10)所示的化合物的粗品,进一步以硅胶与石油醚和乙酸乙酯形成的洗脱体系进行柱层析
纯化,最终得到式(2‑10)所示的化合物纯品;
500mL*5的乙酸乙酯萃取,合并有机相,干燥浓缩后得到式(2‑11)所示的化合物。
继续保持温度在‑5~0℃,滴加完毕,升温至室温,反应完毕,分液除去水相,有机相以饱和
食盐水洗涤,无水硫酸钠干燥,并且减压浓缩后,得到式(2‑1)所示的化合物粗品,然后加入
乙酸乙酯,搅拌成均匀的浆液后过滤,滤饼干燥后,得到式(2‑1)所示的化合物纯品。
32)、式(3‑33)、式(3‑34)、式(3‑35)、式(3‑36)、式(3‑37)、式(3‑38)、式(3‑39)、式(3‑40)、
式(3‑41)、式(3‑42)、式(3‑43)、式(3‑44)、式(3‑45)、式(3‑46)、式(3‑47)、式(3‑48)、式(3‑
49)、式(3‑50)、式(3‑51)、式(3‑52)、式(3‑53)所示的化合物的制备方法。
反应6h。反应完毕后经过萃取、洗涤、浓缩,柱层析纯化得到式(3‑1)所示的化合物。
反应6h。反应完毕后经过萃取、洗涤、浓缩,柱层析纯化得到式(3‑36)所示的化合物。
(m,1H),5.56(s,2H),4.60(d,J=13.2Hz,1H),4.08(d,J=13.6Hz,1H),3.82(dd,J=17.2,
12.0Hz,1H),3.64(dd,J=17.2,9.2Hz,1H),3.46–3.32(m,2H),2.99–2.87(m,1H),2.32(d,J
13
=12.8Hz,1H),2.20(d,J=12.8Hz,1H),2.02–1.78(m,2H). C NMR(100MHz,CDCl3)δ
186.79,174.22,174.15,164.05,162.58(d,J=8.1Hz,1H),160.08(d,J=8.1Hz,1H),
152.22,150.01,145.18,142.59,131.62,130.62(t,J=10.1Hz,1H),120.07,117.97,
115.70(t,J=16.2Hz,1H),113.77,111.97(d,J=6.1Hz,1H),,111.78(d,J=6.1Hz,1H),
+
72.87,49.14,44.73,42.09,41.53,40.18,32.46,31.74.HRMS计算值C27H22F2N6O2S[M+Na]
559.13344.实测值559.13344.
4.8Hz,1H),6.92(t,J=8.1Hz,2H),6.08(dd,J=12.0,9.0Hz,1H),5.37(s,2H),4.61(d,J=
13.8Hz,1H),4.06(d,J=13.8Hz,1H),3.81(dd,J=17.4,12.0Hz,1H),3.64(dd,J=17.4,
9.0Hz,1H),3.29‑3.34(m,2H),2.85(t,J=12.6Hz,1H),2.59(s,3H),2.24(d,J=13.8Hz,
13
1H),2.15(d,J=13.8Hz,1H),1.80‑1.75(m,2H);C NMR(150MHz,CDCl3)δ174.15,164.86,
161.65(d,J=4.5Hz),160.00(d,J=4.5Hz),151.86,151.15,148.24,144.58,141.25,
130.25(t,J=9.1Hz),129.32,117.76,115.77,115.25(t,J=16.2Hz),114.96,111.50(d,J
=3.0Hz),111.36(d,J=3.0Hz),72.37,47.64,44.12,41.45,41.03,39.80,32.00,31.38,
+
12.11.HRMS计算值C26H24F2N6O2S[M+H]523.17223.实测值523.17055.
=8.4Hz,2H),6.02(dd,J=12.0,8.4Hz,1H),5.70(q,J=16.8Hz,2H),4.34(d,J=13.2Hz,
1H),4.13(d,J=13.6Hz,1H),3.91(dd,J=17.2,12.0Hz,1H),3.55(dd,J=17.2,8.8Hz,
1H),3.45‑3.35(m,2H),2.85(t,J=11.6Hz,1H),2.17(d,J=12.0Hz,1H),2.09(d,J=
13
12.0Hz,1H),1.95‑1.83(m,1H),1.66‑1.53(m,1H). C NMR(100MHz,CDCl3)δ174.22,
163.96,162.55(d,J=8.1Hz),160.05(d,J=8.1Hz),152.25,151.06,150.17,145.11,
133.72(q,J=39.4Hz),130.58(t,J=10.1Hz),129.54,122.58,119.90,118.90,117.92,
115.68(t,J=16.2Hz),112.32,111.93(t,J=6.1Hz),111.74(t,J=6.1Hz),72.84,48.99,
+
44.62,41.98,41.51,40.16,32.41,31.74.HRMS计算值C26H21F5N6O2S[M+Na]599.12591.实测
值599.12602.
=8.0,4.8Hz,1H),6.92(t,J=8.4Hz,2H),6.08(dd,J=12.0,9.2Hz,1H),5.40(s,2H),4.61
(d,J=13.6Hz,1H),4.06(d,J=13.6Hz,1H),3.81(dd,J=17.2,12.0Hz,1H),3.64(dd,J=
17.2,9.2Hz,1H),3.38–3.25(m,2H),2.96(t,J=7.6Hz,2H),2.85(t,J=12.0Hz,1H),2.19
13
(dd,J=28.0,13.2Hz,2H),1.88–1.74(m,4H),1.00(t,J=7.6Hz,3H). C NMR(100MHz,
CDCl3)δ174.46,173.92,165.21,162.61(d,J=7.1Hz),160.11(d,J=7.1Hz),152.29,
151.44,148.44,146.04,145.13,130.59(d,J=10.1Hz),130.17,117.82,116.16,115.77
(d,J=16.2Hz),115.20,111.97(d,J=5.1Hz),111.78(d,J=6.1Hz),72.87(t,J=3.0Hz),
48.34,44.65,41.97,41.59,41.57,40.35,32.49,31.86,29.63,22.46,20.92,14.08.HRMS
+
计算值C28H28F2N6O2S[M+H]551.20353.实测值551.20533.
(t,J=10.8Hz,1H),5.36(d,J=15.6Hz,1H),5.32(d,J=16.8Hz,1H),4.58(d,J=13.8Hz,
1H),4.05(d,J=13.8Hz,1H),3.77(t,J=14.8Hz,1H),3.61(dd,J=17.4,9.0Hz,1H),3.32–
3.22(m,2H),2.81(t,J=13.2Hz,1H),2.14(dd,J=26.8,13.2Hz,2H),1.75(t,J=12.6Hz,
13
2H),1.48(s,9H). C NMR(150MHz,CDCl3)δ174.47,165.37,162.27,160.61,152.98,
152.36,151.98,148.22,145.21,131.37,130.61,117.77,115.82,113.42,111.99,111.84,
72.91,48.43,44.79,41.99,41.64,40.40,34.23,32.52,31.94,30.11.HRMS计算值
+
C29H30F2N6O2S[M+H]565.21918.实测值565.21901.
2H),6.08(dd,J=12.0,9.6Hz,1H),5.52(s,2H),4.60(d,J=13.6Hz,1H),4.07(d,J=
13.6Hz,1H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.50–3.28(m,
2H),2.98–2.80(m,1H),2.71(s,3H),2.31(d,J=12.4Hz,1H),2.19(d,J=12.4Hz,1H),
13
2.02–1.76(m,2H). C NMR(150MHz,CDCl3)δ194.39,174.10,164.09,161.95,160.28,
152.05,151.48,149.26,144.94,141.89,132.16,130.50(t,J=7.1Hz),119.48,117.93,
115.49(t,J=10.1Hz),114.29,111.78,111.63,72.67,48.92,44.52,41.84,41.32,40.01,
+
32.27,31.59,26.27.HRMS计算值C27H24F2N6O3S[M+Na]573.14909.实测值573.14878.
4.8Hz,1H),7.00(dd,J=18.0,11.6Hz,1H),6.92(t,J=8.4Hz,2H),6.13–6.01(m,2H),5.56
(d,J=11.6Hz,1H),5.40(s,2H),4.60(d,J=13.2Hz,1H),4.06(d,J=13.2Hz,1H),3.81
(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.32(t,J=11.6Hz,2H),2.86(t,
13
J=12.0Hz,1H),2.23(d,J=13.2,1H),2.16(d,J=13.2,1H),1.92–1.74(m,2H). C NMR
(100MHz,CDCl3)δ174.38,164.91,162.61(d,J=8.1Hz),160.12(d,J=8.1Hz),152.29,
151.77,148.86,145.15,142.67,130.60(t,J=10.1Hz),130.56,129.08,117.85,117.61,
117.30,115.76(t,J=16.2Hz),113.80,111.98(d,J=6.1Hz),111.79(t,J=6.1Hz),72.87
(t,J=3.0Hz),48.42,44.67,41.99,41.56,40.31,32.50,31.82.HRMS计算值C27H24F2N6O2S
+
[M+H]535.17223.实测值535.17301.
6.91(t,J=8.0Hz,2H),6.12–5.92(m,1H),5.44(s,2H),4.57(d,J=12.8Hz,1H),4.05(d,J
=13.2Hz,1H),3.87–3.71(dd,J=17.2,8.4Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.40(s,
13
1H),3.37–3.20(m,2H),2.87(t,J=11.6Hz,1H),2.26–2.11(m,2H),1.95–1.72(m,2H). C
NMR(100MHz,CDCl3)δ174.28,164.44,162.64(d,J=7.1Hz),160.14(d,J=7.1Hz),152.32,
150.76,149.65,145.20,130.58(t,J=11.1Hz),129.83,127.41,117.98,117.81,117.44,
115.79(t,J=16.2Hz),111.98(d,J=5.1Hz),111.78(d,J=5.1Hz),81.80,74.79,72.89,
+
48.81,44.69,42.01,41.59,40.25,32.48,31.80.HRMS计算值C27H22F2N6O2S[M+H]
533.15658.实测值533.15512.
1H),7.17(t,J=9.0Hz,2H),6.01(t,J=10.8Hz,1H),5.84(d,J=16.8Hz,1H),5.77(d,J=
16.8Hz,1H),4.33(d,J=13.8Hz,1H),4.12(d,J=13.8Hz,1H),3.91(dd,J=17.4,13.2Hz,
1H),3.55(dd,J=17.4,8.4Hz,1H),3.46–3.38(m,2H),2.87(t,J=12.6Hz,1H),2.18(d,J=
13
13.2Hz,1H),2.10(d,J=13.8Hz,1H),1.96–1.86(m,1H),1.64–1.56(m,1H). C NMR
(100MHz,DMSO‑d6)δ175.11,163.84,162.04(d,J=8.1Hz),159.56(d,J=8.1Hz),152.25,
151.41,150.87,145.61,144.42,131.53(t,J=10.1Hz),130.54,121.99,120.15,115.73
(t,J=16.2Hz),112.43(d,J=6.1Hz),112.24(d,J=6.1Hz),108.59,72.16,49.87,44.15,
+
41.49,41.26,39.46,32.29,31.86.HRMS计算值C25H21F2N7O4S[M+Na] 576.1236.实测值
576.12505.
=8.4Hz,2H),6.08(dd,J=12.0,9.0Hz,1H),5.46(s,2H),4.60(d,J=13.8Hz,1H),4.07(d,
J=13.8Hz,1H),3.88–3.73(m,2H),3.63(dd,J=17.4,9.0Hz,1H),3.39–3.35(m,1H),2.91
13
(t,J=12.0Hz,1H),2.27(d,J=13.2Hz,1H),2.18(d,J=13.2Hz,1H),1.98–1.86(m,2H). C
NMR(100MHz,CDCl3)δ174.28,164.46,162.49(d,J=8.1Hz),159.99(d,J=8.1Hz),152.15,
151.53,149.43,145.01,132.20,130.57(t,J=10.1Hz),118.97,118.05,115.59(t,J=
16.2Hz),114.79,111.93,111.69,72.79,48.80,44.70,41.99,41.41,40.09,32.36,
+
31.71.HRMS计算值C26H21F2N7O2S[M+H]566.21443.实测值566.21471.
4.8Hz,1H),6.92(t,J=8.4Hz,2H),6.09(dd,J=12.0,9.0Hz,1H),5.43(s,2H),4.59(d,J=
13.7Hz,1H),4.04(d,J=13.8Hz,1H),3.82(dd,J=17.4,12.0Hz,1H),3.64(dd,J=17.4,
9.0Hz,1H),3.34(t,J=12.0Hz,2H),2.87(t,J=12.6Hz,1H),2.28(d,J=12.8Hz,1H),2.17
13
(d,J=13.6Hz,1H),1.90(q,J=12.6Hz,1H),1.80(q,J=12.6Hz,1H);C NMR(150MHz,
CDCl3)δ174.14,164.21,161.82(d,J=7.6Hz),160.15(d,J=7.6Hz),152.00,151.07,
149.87(d,J=7.6Hz),144.74,130.38(d,J=10.6Hz),129.34,119.82,117.87,117.49,
115.79,115.38(d,J=15.2Hz),111.65(d,J=4.5Hz),111.51(d,J=4.5Hz),72.52,48.31,
+
44.28,41.64,41.20,39.88,32.13,31.48.HRMS计算值C25H21BrF2N6O2S[M+Na]609.04904.实
测值609.04743.
8.4,4.8Hz,1H),6.91(t,J=8.4Hz,2H),6.07(t,J=10.6Hz,1H),5.44(s,2H),4.60(d,J=
13.8Hz,1H),4.07(d,J=13.8Hz,1H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,
9.0Hz,1H),3.32(t,J=12.0Hz,2H),2.85(t,J=12.6Hz,1H),2.23(d,J=13.8Hz,1H),2.15
13
(d,J=13.8Hz,1H),1.90–1.81(m,2H). C NMR(100MHz,CDCl3)δ174.21,164.78,162.31(d,
J=8.1Hz),159.81(d,J=8.1Hz),152.05,150.59,148.56,144.83,132.85,130.40(t,J=
11.1Hz),130.20,117.81,116.81,115.48,115.47(t,J=16.2Hz),111.72(d,J=5.1Hz),
111.53(d,J=5.1Hz),72.59(t,J=3.0Hz),48.24,44.37,41.66,41.27,40.00,32.22,
+
31.56.HRMS计算值C25H22F2N6O2S[M+H]509.15658.实测值509.15668.
7.17(t,J=8.4Hz,2H),6.01(dd,J=12.0,8.4Hz,1H),5.58(d,J=16.8Hz,1H),5.50(d,J=
16.8Hz,1H),4.33(d,J=13.2Hz,1H),4.13(d,J=13.2Hz,1H),3.91(dd,J=17.2,12.0Hz,
1H),3.55(dd,J=17.2,8.4Hz,1H),3.45‑3.35(m,2H),2.83(t,J=12.6Hz,1H),2.15(d,J=
13
13.2Hz,1H),2.09(d,J=13.2Hz,1H),1.88‑1.80(m,1H),1.57(d,J=12.0Hz,1H). C NMR
(150MHz,CDCl3)δ174.16,164.58,162.13,160.51,152.21,151.11,148.95,145.16,
132.98,130.52,126.80,120.24,117.75,111.90,111.75,72.83,48.81,44.62,41.94,
+
41.52,40.21,32.44,31.73.HRMS计算值C25H21BrF2N6O2S[M+Na] 609.04904,实测值
609.04777.
6.02(dd,J=12.0,8.4Hz,1H),5.57(d,J=16.8,1H),5.47(d,J=16.8,1H),4.33(d,J=
13.2Hz,1H),4.13(d,J=13.2Hz,1H),3.91(dd,J=17.4,12.0Hz,1H),3.55(dd,J=17.4,
8.4Hz,1H),3.47‑3.35(m,1H),3.34‑3.26(m,1H),2.83(t,J=12.6Hz,1H),2.15(d,J=
13
13.2Hz,1H),2.09(d,J=13.2Hz,1H),1.90‑1.75(m,1H),1.65‑1.50(m,1H). C NMR
(100MHz,DMSO)δ175.12,164.77,162.03(d,J=8.0),159.56(d,J=8.0),152.25,149.07,
144.41,132.58,132.21,131.54(t,J=10.0),120.12,116.93,115.74(d,J=16.2),112.43
(d,J=5.0),112.25(d,J=5.0),112.00,72.16,48.72,44.05,41.36,41.27,32.37,
+
31.90.HRMS计算值C25H21BrF2N6O2S[M+Na]609.04904,实测值609.04935.
8.4Hz,1H),7.17(t,J=8.4Hz,2H),6.02(t,J=10.8Hz,1H),5.54(d,J=16.8Hz,1H),5.45
(d,J=16.8Hz,1H),4.35(d,J=13.2Hz,1H),4.14(d,J=13.2Hz,1H),4.06‑3.98(m,1H),
3.92(dd,J=17.4,12.0Hz,1H),3.55(dd,J=17.4,8.4Hz,1H),3.44‑3.39(m,1H),2.85(t,J
=13.2Hz,1H),2.16(d,J=13.2Hz,1H),2.10(d,J=13.2Hz,1H),1.94‑1.82(m,1H),1.68‑
13
1.57(m,1H). C NMR(100MHz,DMSO)δ175.05,164.70,161.99(d,J=8.0),159.51(d,J=
8.0),152.22,150.34,144.36,140.62,133.42,133.20,131.46(t,J=10.0),120.76,
119.96,115.68(t,J=16.2),114.39,112.37(d,J=5.0),112.17(d,J=5.0),72.11,
+
48.62,44.03,41.33,41.24,32.33,31.81.HRMS计算值C25H21BrF2N6O2S[M+Na]609.04904,实
测值609.04888.
(dd,J=12.0,9.6Hz,1H),5.46(s,2H),4.60(d,J=13.2Hz,1H),4.07(d,J=13.2Hz,1H),
3.88‑3.73(m,2H),3.66‑3.60(m,1H),3.39‑3.35(m,1H),2.93‑2.87(m,1H),2.27(d,J=
13
13.2Hz,1H),2.18(d,J=13.2Hz,1H),1.98‑1.86(m,2H). C NMR(100MHz,CDCl3)δ174.28,
164.46,162.52,162.45,160.02,159.95,152.15,151.53,149.43,145.01,132.20,130.68,
130.57,130.47,118.97,118.05,115.75,115.59,115.43,114.79,111.93,111.69,72.79,
+
48.80,44.70,41.99,41.41,40.09,32.36,31.71.HRMS计算值C26H21F5N6O2S[M+Na]
599.12591,实测值599.12602.
6.03(dd,J=12.0,8.4Hz,1H),5.67(d,J=16.8,1H),5.58(d,J=16.8,1H),4.35(d,J=
13.2Hz,1H),4.16(d,J=13.2Hz,1H),3.93(dd,J=17.2,12.0Hz,1H),3.46‑3.38(m,1H),
3.37‑3.33(t,J=12.6Hz,2H),2.84(t,J=12.0Hz,1H),2.17(d,J=13.2Hz,1H),2.10(d,J
13
=13.2Hz,1H),1.91‑1.85(m,1H),1.61‑1.55(m,1H). C NMR(100MHz,CDCl3)δ174.14,
164.46,162.59(d,J=8.0),160.09(d,J=8.0),152.21,151.81,145.93(t,J=3.0),
134.80,134.08,130.56(t,J=10.0),128.44(q,J=4.0),124.16(q,J=135.0),120.37(q,
J=33.0),117.80,115.72(t,J=16.2),114.45,111.94(d,J=6.0),111.75(d,J=6.0),
72.86(t,J=3.0),48.69,44.65,42.00,41.52,41.49,40.21,32.47,31.73.HRMS计算值
+
C26H21F5N6O2S[M+Na]599.12591,实测值599.12565.
7.17(t,J=8.4Hz,2H),6.01(t,J=10.8Hz,1H),5.65(d,J=16.8Hz,1H),5.55(d,J=
16.8Hz,1H),4.34(d,J=13.2Hz,1H),4.18(d,J=13.2Hz,1H),3.93‑3.88(m,1H),3.57‑
3.52(m,1H),3.45‑3.39(m,1H),3.34(s,1H),2.85(t,J=13.2Hz,1H),2.17(d,J=9.6Hz,
13
1H),2.11(d,J=9.6Hz,1H),1.65‑1.50(m,2H). C NMR(150MHz,CDCl3)δ174.20,164.69,
162.20,160.53,152.29,149.99,145.16,133.27,133.10,131.88,130.54,117.81,117.28,
113.25,111.92,111.76,72.85,48.24,44.76,42.00,41.54,40.24,36.80,32.47,31.75,
+
20.34.HRMS计算值C26H21F5N6O2S[M+Na]599.12591,实测值599.12762.
7.50–7.46(m,1H),7.38–7.30(m,2H),6.29(td,J=11.6,4.0Hz,1H),5.28(s,2H),4.60(d,J
=13.2Hz,1H),4.15(d,J=13.6Hz,1H),3.84(ddd,J=16.8,12.0,4.0Hz,1H),3.66(ddd,J
=16.4,10.4,4.0Hz,1H),3.37(q,J=12.4,11.2Hz,2H),3.25(d,J=4.0Hz,3H),2.91(t,J
=13.2Hz,1H),2.29(d,J=13.2Hz,1H),2.19–2.13(m,1H),1.95–1.85(m,1H),1.81–1.76
13
(m,1H). C NMR(100MHz,CDCl3)δ185.03,174.34,164.78,152.89,148.63,148.36,145.00,
144.76,140.09,135.25,130.94,130.29,129.73,129.14,121.26,119.10,118.45,117.44,
116.95,45.33,44.90,42.15,41.91,40.19,37.99,32.48,31.79.HRMS(ESI)计算值
+
C27H25ClN6O6S2[M+Na]:651.0858,实测值651.0832.
(m,2H),7.12(dt,J=8.0,3.6Hz,1H),6.37–6.22(m,1H),5.39(d,J=3.2Hz,2H),4.63(d,J
=13.2Hz,1H),4.09(d,J=13.6Hz,1H),3.86(ddd,J=16.4,12.4,3.2Hz,1H),3.67(ddd,J
=17.2,11.2,3.2Hz,1H),3.40–3.30(m,2H),3.25(d,J=3.2Hz,3H),2.87(t,J=12.8Hz,
1H),2.61(d,J=3.2Hz,3H),2.22(q,J=14.0,13.2Hz,2H),1.82(dt,J=24.4,12.8Hz,2H)
13
. C NMR(100MHz,CDCl3)174.61,165.27,152.96,151.60,148.70,144.95,141.87,135.22,
130.19,129.82,128.99,121.24,118.22,116.19,115.57,48.17,44.64,42.00,41.95,
40.35,38.02,32.51,32.45,31.86,31.80,29.67,12.55.HRMS(ESI)计算值C27H27ClN6O5S2[M
+
+Na]:637.1065,实测值637.1062.
3H),6.31(t,J=11.6Hz,1H),5.54(s,2H),4.61(d,J=13.6Hz,1H),4.08(d,J=13.6Hz,
1H),3.88(dd,J=17.2,12.4Hz,1H),3.68(dd,J=17.2,10.8Hz,1H),3.40(td,J=12.4,
10.8,4.8Hz,2H),3.27(s,3H),2.92(t,J=12.8Hz,1H),2.32(d,J=13.2Hz,1H),2.21(d,J
13
=11.2Hz,1H),1.96(d,J=12.0Hz,1H),1.84(q,J=12.4,11.6Hz,1H). C NMR(100MHz,
CDCl3)174.36,163.99,152.96,151.15,150.20,148.71,145.01,135.24,133.87(q,J=
39.3Hz),130.21,129.74,129.61,129.02,125.29,122.61,121.24,119.93,118.91,
118.25,117.26,112.41,49.02,44.69,42.01,40.24,38.01,32.44(d,J=5.6Hz),31.78(d,
+
J=5.1Hz).HRMS(ESI)计算值C27H24ClF3N6O5S2[M+Na]:691.0782,实测值691.0794.
8.4Hz,1H),7.33(t,J=8.4Hz,1H),7.11(dd,J=7.8,4.8Hz,1H),6.28(t,J=11.4Hz,1H),
5.41(s,2H),4.60(d,J=14.4Hz,1H),4.06(d,J=14.4Hz,1H),3.83(dd,J=17.2,12.0Hz,
1H),3.64(dd,J=17.2,10.8Hz,1H),3.34–3.28(m,2H),3.22(s,3H),2.95(t,J=7.6Hz,
2H),2.85(t,J=12.6Hz,1H),2.22(d,J=12.6Hz,1H),2.15(d,J=15.0Hz,1H),1.84(q,J=
13
7.2Hz,4H),1.00(t,J=7.2Hz,3H). C NMR(100MHz,CDCl3)δ182.13,174.69,165.25,
152.99,151.56,148.70,148.53,146.04,144.93,135.25,130.23,129.73,129.02,121.27,
118.28,116.17,115.15,66.83,59.08,48.32,44.67,42.00,40.38,38.00,32.45,31.88,
+
29.66,22.46,14.08.HRMS(ESI)计算值C29H31ClN6O5S2[M+Na]:665.1378,实测值665.1383.
2H),7.09(m,1H),6.37–6.20(m,1H),5.39(t,J=4.8Hz,2H),4.64(d,J=13.6Hz,1H),4.11
(d,J=13.6Hz,1H),3.86–3.72(m,1H),3.67–3.51(m,1H),3.39–3.29(m,2H),3.25(d,J=
5.6Hz,3H),2.85–2.74(m,1H),2.20(q,J=13.2,9.6Hz,2H),1.83–1.71(m,2H),1.53(d,J=
13
5.6Hz,9H). C NMR(100MHz,CDCl3)δ174.72,165.33,160.00,152.99,151.82,148.69,
148.07,144.92,139.33,135.24,131.49,130.24,129.74,129.04,121.28,118.28,117.25,
115.79,113.49,59.40,48.45,44.75,42.00,41.28,40.39,38.01,34.20,32.43,31.90,
+
30.08.HRMS(ESI)计算值C30H33ClN6O5S2[M+Na]:679.1535,实测值679.1537.
2H),6.13(dd,J=12.4,9.2Hz,1H),5.64(s,2H),4.71(d,J=13.2Hz,1H),4.22(d,J=
13.2Hz,1H),3.83(dd,J=17.6,12.4Hz,1H),3.71(dd,J=17.6,9.2Hz,1H),3.61–3.32(m,
2H),3.27(s,3H),2.91–2.73(m,1H),2.67(s,3H),2.45(d,J=12.0Hz,1H),2.23(d,J=
13
12.0Hz,1H),2.14–1.80(m,2H). C NMR(100MHz,CDCl3)δ190.42,176.33,165.45,163.25,
161.81,154.25,153.60,150.24,146.11,142.07,134.37,131.16(t,J=7.2Hz),121.51,
118.56,116.35(t,J=10.7Hz),114.58,112.30,111.79,73.06,50.49,45.78,42.15,
41.87,40.83,37.50,34.59,32.57,28.38.
10.4Hz,1H),6.89(t,J=8.0Hz,2H),6.72(d,J=16.8Hz,1H),6.32(dd,J=12.0,9.2Hz,
1H),5.68(d,J=11.2Hz,1H),5.33(d,J=4.0Hz,2H),4.57(d,J=13.5Hz,1H),4.13(d,J=
13.9Hz,1H),3.72(dd,J=17.1,12.0Hz,1H),3.57(dd,J=17.1,9.2Hz,1H),3.41(td,J=
11.5,5.4Hz,2H),3.11–2.63(m,1H),2.18(t,J=15.7Hz,2H),1.81(pd,J=12.1,4.0Hz,
13
2H). C NMR(100MHz,CDCl3)δ175.44,166.75,163.70(d,J=8.4Hz),161.18(d,J=8.4Hz),
155.31,152.82,149.92,146.21,142.95,131.54(t,J=10.0Hz),130.67,129.48,117.91,
117.67,117.35,115.84(t,J=17.6Hz),114.02,111.26(d,J=7.2Hz),111.03(t,J=
7.2Hz),72.23(t,J=4.2Hz),50.39,46.72,42.87,42.60,40.64,38.09,33.89,31.99.
6.98(t,J=8.4Hz,2H),6.26–6.06(m,1H),5.50(s,2H),4.61(d,J=12.8Hz,1H),4.11(d,J
=12.8Hz,1H),3.90–3.75(dd,J=17.6,8.4Hz,1H),3.66(dd,J=17.6,8.8Hz,1H),3.60(s,
3H),3.49(s,1H),3.35–3.16(m,2H),2.92(t,J=12.0Hz,1H),2.34–2.19(m,2H),1.98–1.78
13
(m,2H). C NMR(100MHz,CDCl3)δ175.33,166.74,163.87(d,J=7.2Hz),161.25(d,J=
7.2Hz),155.42,151.69,150.13,146.15,131.69(t,J=11.9Hz),130.02,128.51,118.91,
118.80,117.65,116.31(t,J=15.8Hz),112.05(d,J=5.7Hz),111.84(d,J=5.7Hz),
83.48,75.80,72.97,50.15,46.82,43.21,41.87,40.47,38.11,33.02,32.19.
2H),7.45–7.34(m,2H),6.32(dd,J=12.0,10.4Hz,1H),5.62(d,J=2.0Hz,2H),4.64–4.56
(m,1H),4.08(d,J=13.6Hz,1H),3.89(dd,J=17.2,12.4Hz,1H),3.69(dd,J=17.2,
10.8Hz,1H),3.49–3.37(m,2H),3.28(s,3H),2.95(t,J=13.2Hz,1H),2.37(d,J=13.2Hz,
13
1H),2.22(d,J=12.8Hz,1H),2.04–1.98(m,1H),1.86(dd,J=13.6,9.6Hz,1H). C NMR
(100MHz,CDCl3)δ178.65,165.62,157.58,153.78,151.45,147.88,142.26,137.64,
135.57,134.25,133.79,132.08,128.06,127.52,124.36,122.97,118.88,115.72,106.51,
+
56.64,49.63,45.47,43.76,37.24,33.68,32.74.HRMS(ESI)计算值C26H24ClN7O7S2[M+Na] :
630.1779,实测值630.1792.
1H),7.43–7.31(m,3H),6.29(dd,J=12.2,10.6Hz,1H),5.52(s,2H),4.57(d,J=13.6Hz,
1H),4.04(d,J=13.8Hz,1H),3.85(dd,J=17.3,12.2Hz,1H),3.65(dd,J=17.3,10.6Hz,
1H),3.39(qd,J=11.7,11.2,3.3Hz,2H),3.23(s,3H),2.98–2.84(m,1H),2.37–2.29(m,
13
1H),2.24–2.16(m,1H),1.96(q,J=12.0Hz,1H),1.83(qd,J=12.0,4.1Hz,1H). C NMR
(100MHz,CDCl3)δ174.23,163.62,152.94,150.66,148.71,145.04,135.26,130.24,
129.73,129.15,129.05,121.25,119.69,118.30,117.93,117.04,112.78,49.35,44.73,
42.05(d,J=11.4Hz),40.19,37.99,32.45(d,J=5.0Hz),31.73(d,J=5.0Hz).
16.0,8.0Hz,2H),7.23(dd,J=8.0,4.4Hz,1H),6.30(t,J=11.2Hz,1H),5.43(s,2H),4.60
(d,J=13.2Hz,1H),4.06(d,J=13.6Hz,1H),3.86(dd,J=17.2,12.4Hz,1H),3.67(dd,J=
17.2,10.4Hz,1H),3.36(t,J=12.0Hz,2H),3.26(s,3H),2.89(t,J=12.4Hz,1H),2.29(d,J
13
=13.2Hz,1H),2.18(d,J=10.4Hz,1H),1.84(dt,J=38.8,13.2Hz,2H). C NMR(150MHz,
CDCl3)δ170.91,160.88,149.35,147.79,146.53,145.08,141.36,131.64,126.64,126.27,
126.14,125.45,117.66,116.79,114.75,114.18,112.71,45.11,41.22–40.88(m),38.41,
36.68,34.45,28.88(d,J=8.5Hz),28.21(d,J=7.4Hz).HRMS(ESI)计算值C26H24BrClN6O5S2
+
[M+Na]:701.0014,实测值701.0015.
=8.0Hz,1H),7.33(t,J=8.2Hz,1H),7.15(dd,J=8.0,4.5Hz,1H),6.27(dd,J=12.2,
10.6Hz,1H),5.44(s,2H),4.60(d,J=13.6Hz,1H),4.06(d,J=13.8Hz,1H),3.83(dd,J=
17.2,12.2Hz,1H),3.63(dd,J=17.2,10.6Hz,1H),3.32(tt,J=11.1,3.4Hz,2H),3.22(s,
3H),2.89–2.82(m,1H),2.24(d,J=13.4Hz,1H),2.15(d,J=13.4Hz,1H),1.88–1.74(m,
13
2H). C NMR(150MHz,CDCl3)δ174.53,164.95,152.93,150.77,148.76,148.64,144.90,
135.20,133.17,130.49,130.17,129.67,128.97,121.21,118.22,117.04,115.78,48.49,
44.64,41.94,40.31,37.93,32.46(d,J=9.9Hz),31.78(d,J=9.8Hz).
7.33(dd,J=9.3,6.6Hz,2H),6.30–6.24(m,1H),5.41(s,2H),4.59(d,J=13.6Hz,1H),4.04
(d,J=13.8Hz,1H),3.83(dd,J=17.3,12.2Hz,1H),3.64(dd,J=17.2,10.6Hz,1H),3.36–
3.29(m,2H),3.22(s,3H),2.90–2.83(m,1H),2.26(d,J=13.6Hz,1H),2.16(d,J=13.6Hz,
13
1H),1.88(t,J=12.4Hz,1H),1.78(s,1H). C NMR(150MHz,CDCl3)δ174.38,164.57,
152.91,151.13,148.98,148.64,144.93,135.20,133.04,130.18,129.67,128.98,126.83,
121.21,120.27,118.23,117.77,48.82,44.63,41.94,40.25,37.93,32.48,32.41,31.78,
31.72.
7.38(d,J=8.1Hz,1H),7.32(t,J=8.2Hz,1H),6.29–6.23(m,1H),5.39(s,2H),4.57(d,J=
13.6Hz,1H),4.03(d,J=13.7Hz,1H),3.82(dd,J=17.3,12.2Hz,1H),3.63(dd,J=17.3,
10.6Hz,1H),3.32(tt,J=11.5,3.6Hz,2H),3.21(s,3H),2.89–2.81(m,1H),2.25(d,J=
13.4Hz,1H),2.15(d,J=13.4Hz,1H),1.86(dd,J=12.0,6.5Hz,1H),1.77(tt,J=12.5,
13
6.6Hz,1H). C NMR(150MHz,CDCl3)δ170.47,160.66,148.95,145.78,145.44,144.70,
140.97,131.26,128.43,128.15,126.24,125.72,125.05,117.26,114.30,113.18,108.80,
44.69,40.75,40.67,38.00,36.31,36.25,34.02,33.96.
7.35(dd,J=9.0,6.6Hz,2H),6.53–6.31(m,1H),5.54(s,2H),4.69(d,J=13.8Hz,1H),4.23
(d,J=13.8Hz,1H),3.61(dd,J=17.4,12.6Hz,1H),3.60(dd,J=17.4,10.8Hz,1H),3.42–
3.30(m,2H),3.31(s,3H),2.99–2.75(m,1H),2.33(d,J=13.8Hz,1H),2.21(d,J=13.7Hz,
13
1H),1.76(t,J=12.8Hz,1H),1.73(s,1H). C NMR(150MHz,CDCl3)δ176.44,166.37,
153.81,152.16,149.68,148.56,145.67,136.62,134.26,132.31,130.74,129.51,126.66,
123.31,121.19,118.57,118.03,50.62,45.33,42.48,41.37,38.06,33.62,33.32,32.19,
31.89.
7.31(dd,J=9.6,6.0Hz,2H),6.53–6.48(m,1H),5.62(s,2H),4.71(d,J=12.6Hz,1H),4.32
(d,J=12.8Hz,1H),4.03(dd,J=17.4,12.0Hz,1H),3.76(dd,J=17.4,10.4Hz,1H),3.40–
3.34(m,2H),3.25(s,3H),2.99–2.92(m,1H),2.38(d,J=13.8Hz,1H),2.20(d,J=13.8Hz,
13
1H),1.90(t,J=12.6Hz,1H),1.81(s,1H). C NMR(150MHz,CDCl3)δ174.40,166.62,
154.81,152.06,149.11,148.76,145.86,137.61,134.63,131.20,130.29,129.05,127.74,
122.38,121.37,119.64,118.58,50.31,46.52,43.71,41.52,39.26,34.27,34.20,32.59,
31.72.
8.0Hz,1H),7.32–7.23(m,2H),6.26–6.11(m,1H),5.40(d,J=2.4Hz,2H),4.50(d,J=
13.6Hz,1H),3.99(d,J=13.6Hz,1H),3.82–3.70(m,1H),3.57(ddd,J=17.2,10.8,2.4Hz,
1H),3.28(q,J=11.2,10.0Hz,2H),3.15(d,J=2.4Hz,3H),2.81(t,J=12.8Hz,1H),2.22
13
(d,J=13.2Hz,1H),2.13–2.04(m,1H),1.84(d,J=11.6Hz,1H),1.73(d,J=12.4Hz,1H). C
NMR(100MHz,CDCl3)δ205.86,174.43,164.52,152.95,151.85,148.69,145.99,145.00,
135.26,134.13,130.26,129.74,129.07,128.52,122.87,121.27,120.44(q,J=32.6Hz),
118.35,114.51,66.96,48.73,44.70,41.98,40.27,38.00,32.47,31.80.HRMS(ESI)计算值
+
C27H24ClF3N6O5S2[M+Na]:691.0782,实测值691.0781.
1H),5.52(d,J=3.6Hz,2H),4.63(d,J=13.2Hz,1H),4.14(d,J=13.6Hz,1H),3.89(ddd,J
=16.8,12.4,3.6Hz,1H),3.69(ddd,J=17.2,10.8,3.6Hz,1H),3.48–3.34(m,2H),3.28(d,
J=4.0Hz,3H),3.00–2.86(m,1H),2.34(d,J=13.2Hz,1H),2.27–2.18(m,1H),2.06–1.78
13
(m,2H). C NMR(100MHz,CDCl3)δ174.52,164.74,152.99,150.05,148.71,146.91,146.54,
144.99,135.27,133.36,131.96,130.26,129.74,129.06,121.28,120.32,118.35,117.36,
113.33,59.23,48.29,44.82,42.03,40.33,38.01,32.50,31.84.HRMS(ESI)计算值
+
C27H24ClF3N6O5S2[M+Na]:691.0782,实测值691.0780.
入20mL饱和氯化铵进行淬灭,加入10mL,反应体系以乙酸乙酯萃取,有机相经干燥,浓缩,柱
层析得到式(3‑2)所示的化合物。
6.4Hz,1H),7.22(dd,J=8.0,4.8Hz,1H),7.17(t,J=8.4Hz,2H),6.56(s,1H),6.07–5.96
(m,1H),5.54–5.34(m,3H),4.79(d,J=5.2Hz,2H),4.35(d,J=13.2Hz,1H),4.15(d,J=
13.2Hz,1H),3.92(dd,J=17.2,12.0Hz,1H),3.55(dd,J=17.2,8.4Hz,1H),3.45–3.36(m,
1H),2.82(t,J=11.6Hz,1H),2.12(dd,J=23.6,12.8Hz,2H),1.83(q,J=10.4,9.6Hz,1H),
13
1.64–1.48(m,1H). C NMR(100MHz,DMSO‑d6)δ175.11,165.09,162.01(d,J=8.1Hz),
159.53(d,J=8.1Hz),152.23,151.39,148.62,144.64,144.39,131.49(t,J=11.1Hz),
130.58,120.05,116.54,115.71(t,J=16.2Hz),113.97,112.40(d,J=6.1Hz),112.20(d,J
=6.1Hz),72.13,59.55,57.20,48.90,48.09,44.02,41.28(d,J=4.0Hz),32.39,
+
31.91.HRMS计算值C26H24F2N6O3S[M+H]539.16714.实测值539.17034.
完毕。升至室温,加入10mL水,体系以乙酸乙酯萃取,有机相经干燥,浓缩,柱层析得到式(3‑
3)所示的化合物。
6.4Hz,1H),7.25(dd,J=8.0,4.8Hz,1H),7.17(t,J=8.4Hz,2H),6.02(dd,J=12.0,8.4Hz,
1H),5.53(d,J=16.8Hz,1H),5.44(d,J=16.8Hz,1H),4.73(s,2H),4.34(d,J=13.2Hz,
1H),4.15(d,J=13.2Hz,1H),3.92(dd,J=17.2,12.0Hz,1H),3.55(dd,J=17.2,8.4Hz,
1H),3.45–3.36(m,1H),3.31(s,3H),3.27–3.37(m,1H),2.82(t,J=11.6Hz,1H),2.20–2.05
13
(m,2H),1.90–1.75(m,1H),1.64–1.50(m,1H). C NMR(100MHz,DMSO‑d6)δ175.11,165.08,
161.99(d,J=8.1Hz),159.51(d,J=8.1Hz),151.85,151.33,148.55,144.61,142.54,
131.44(t,J=11.6Hz),130.01,123.11,116.51,115.66(t,J=16.2Hz),114.00,112.38(d,
J=6.1Hz),112.17(d,J=6.1Hz),72.09,62.35,58.77,57.14,48.88,48.13,43.98,41.25
+
(d,J=4.0Hz),32.45,32.03.HRMS计算值C27H26F2N6O3S[M+H]553.18279.实测值553.18420.
行淬灭,以二氯甲烷萃取,有机相经干燥,浓缩,柱层析得到式(3‑4)所示的化合物。
8.4Hz,2H),6.08(t,J=10.2Hz,1H),5.43(s,2H),4.95(s,2H),4.59(d,J=12.6Hz,1H),
4.05(d,J=10.8Hz,1H),3.81(dd,J=16.8,12.0Hz,1H),3.63(dd,J=16.8,9.6Hz,1H),
13
3.45–3.20(m,2H),2.87(t,J=12.0Hz,1H),2.34–2.12(m,2H),1.97–1.75(m,2H). C NMR
(150MHz,CDCl3)δ174.21,164.61,161.97,160.30,152.06,151.39,149.05,144.90,
140.86,130.51,130.09,117.94,117.22,115.52,114.07,111.80,111.66,72.68,48.40,
+
44.57,41.85,41.41,40.08,38.24,32.32,31.63.HRMS计算值C26H23ClF2N6O2S[M+H]
557.13326.实测值557.13158.
系倒入20mL水中,以乙酸乙酯萃取,有机相依次以1N稀盐酸和饱和碳酸氢钠洗涤,硫酸钠干
燥,浓缩,柱层析得到式(3‑5)所示的化合物。
1H),7.20–7.10(m,1H),6.90(t,J=7.8Hz,2H),6.07(t,J=10.8Hz,1H),5.44(s,2H),4.59
(d,J=13.8Hz,1H),4.03(d,J=11.4Hz,1H),3.80(dd,J=16.8,9.0Hz,1H),3.63(dd,J=
16.8,9.0Hz,1H),3.32(t,J=11.4Hz,2H),2.88–2.81(m,1H),2.24(d,J=13.2Hz,1H),2.14
13
(d,J=13.2Hz,1H),1.89–1.77(m,2H). C NMR(100MHz,CDCl3)δ174.37,164.80,162.58(d,
J=8.1Hz),160.08(d,J=8.1Hz),152.29,151.72,149.35,145.09,141.04,130.60(t,J=
10.1Hz),130.10,117.92,117.35,115.72(t,J=16.2Hz),114.20,111.97(t,J=6.1Hz),
111.78(t,J=6.1Hz),72.87(t,J=3.0Hz),48.39,44.65,41.99,41.54,40.22,38.33,
+
32.45,31.78.HRMS计算值C26H23F2N7O3S[M+Na]574.14434.实测值574.14738.
毕。升至室温,加入10mL水,体系以乙酸乙酯萃取,有机相经干燥,浓缩,柱层析得到式(3‑6)
所示的化合物。
7.19(m,1H),6.92(t,J=8.4Hz,2H),6.08(t,J=10.8Hz,1H),5.43(s,2H),4.60(d,J=
13.2Hz,1H),4.17–4.01(m,4H),3.81(dd,J=16.8,12.6Hz,1H),3.63(dd,J=16.8,9.0Hz,
1H),3.34(t,J=10.2Hz,2H),2.88(t,J=12.6Hz,1H),2.25(d,J=12.0Hz,1H),2.17(d,J=
13
13.2Hz,1H),1.92–1.77(m,2H). C NMR(100MHz,CDCl3)δ174.30,164.72,162.69(d,J=
8.1Hz),160.19(d,J=8.1Hz),152.34,151.83,149.65,145.26,143.90,138.50,132.65,
130.65(t,J=10.1Hz),118.24,117.86,115.83(t,J=16.2Hz),113.64,112.05(d,J=
6.1Hz),111.85(d,J=6.1Hz),72.94(t,J=3.0Hz),62.60,48.61,44.75,42.08,41.63,
+
40.34,32.57,31.86.HRMS计算值C27H25F2N7O3S[M+Na]588.15999.实测值588.16178.
氯乙烷中,搅拌反应5h,反应完毕,加入20mL水,以二氯甲烷萃取,有机相以饱和碳酸氢钠洗
涤,硫酸钠干燥后,浓缩,并进一步以硅胶柱层析纯化,得到式(3‑7)所示的化合物。
4.8Hz,1H),6.91(t,J=8.4Hz,2H),6.07(dd,J=12.0,9.6Hz,1H),5.41(s,2H),4.57(d,J=
13.2Hz,1H),4.19(s,2H),4.06(d,J=13.2Hz,1H),3.90(s,1H),3.80(dd,J=17.2,12.0Hz,
1H),3.62(dd,J=17.2,9.2Hz,1H),3.40–3.25(m,2H),2.84(t,J=12.4Hz,1H),2.53(s,
13
3H),2.25(d,J=12.4Hz,1H),2.15(d,J=12.4Hz,1H),1.94–1.73(m,2H). C NMR(150MHz,
CDCl3)δ174.37,165.07,162.10(d,J=5.1Hz),160.43(d,J=5.1Hz),152.20,151.54,
149.06,145.04,141.61,130.57(t,J=7.1Hz),130.22,117.93,116.85,115.66,114.53,
111.91,111.75,72.80,48.20,47.24,44.58,41.89,41.46,40.21,35.27,32.42,
+
31.76.HRMS计算值C27H27F2N7O2S[M+H]552.19878.实测值552.19872.
4.8Hz,1H),6.85(t,J=8.4Hz,2H),6.00(d,J=9.6Hz,1H),5.34(s,2H),4.52(d,J=
13.2Hz,1H),4.00(d,J=13.2Hz,1H),3.90(s,2H),3.74(dd,J=17.2,9.6Hz,1H),3.56(dd,
J=13.2,8.4Hz,1H),3.27–3.23(m,2H),2.78(t,J=11.2Hz,1H),2.33(s,6H),2.18(d,J=
13
14.4Hz,1H),2.09(d,J=13.2Hz,1H),1.83–1.70(m,2H). C NMR(150MHz,CDCl3)δ174.25,
164.81,161.95(d,J=5.1Hz),160.28(d,J=5.1Hz),152.09,151.54,148.85,144.89,
141.36,130.46(t,J=7.1Hz),130.39,117.87,116.74,115.51(t,J=10.1Hz),115.09,
111.78,111.63,72.65,55.70,48.13,44.94,44.42,41.75,41.34,40.07,32.29,
+
31.64.HRMS计算值C28H29F2N7O2S[M+H]566.21443.实测值566.21471.
5.16(s,2H),4.50(d,J=13.2Hz,1H),4.23–3.71(m,4H),3.61(dq,J=17.6,9.2Hz,1H),
13
3.34–3.08(m,2H),3.00–2.53(m,2H),2.47–2.04(m,5H),1.91–1.39(m,4H). C NMR
(100MHz,CDCl3)δ174.31,174.06,164.37,162.54(d,J=8.1Hz),160.04(d,J=8.1Hz),
152.24,150.65,149.61,145.07,130.57(t,J=11.1Hz),129.80,127.31,117.95,117.90,
117.37,115.69(t,J=16.2Hz),111.93(d,J=6.1Hz),111.74(d,J=6.1Hz),81.84,74.72,
+
72.81,48.77,44.62,41.96,41.50,40.20,32.44,31.75.HRMS计算值C29H29F2N7O2S[M+H]
578.21443.实测值578.21619.
4.8Hz,1H),6.91(t,J=8.4Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),5.39(s,2H),4.59(d,J=
13.6Hz,1H),4.11–4.00(m,3H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,
1H),3.37–3.24(m,2H),2.84(t,J=11.8Hz,1H),2.73–2.55(m,4H),2.23(d,J=12.8Hz,
13
1H),2.15(d,J=12.8Hz,1H),1.90–1.70(m,6H). C NMR(150MHz,CDCl3)δ174.21,164.80,
161.89(d,J=6.1Hz),160.23(d,J=6.1Hz),152.04,151.40,148.70,144.83,142.15,
130.41(t,J=7.1Hz),130.35,117.81,116.55,115.47(t,J=10.1Hz),114.93,111.71,
111.57,72.59,53.91,52.00,48.06,44.37,41.69,41.28,40.03,32.23,31.59,23.31.HRMS
+
计算值C30H31F2N7O2S[M+H]592.23008.实测值592.23083.
入20mL水,以二氯甲烷萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓缩,并进一步以硅
胶柱层析纯化,得到式(3‑11)所示的化合物。
1H),6.91(t,J=7.8Hz,2H),6.07(dd,J=14.4,6.6Hz,1H),5.64–5.24(m,3H),4.59(d,J=
12.0Hz,1H),4.09–4.03(m,1H),3.82–3.76(m,1H),3.62(dd,J=16.8,9.6Hz,1H),3.33(dd,
J=19.2,8.4Hz,2H),2.88–2.80(m,1H),2.30–2.26(m,1H),2.14–2.09(m,1H),1.87–1.76
13
(m,2H),1.27–1.17(m,4H). C NMR(100MHz,CDCl3)δ174.20,164.11,162.63(d,J=8.1Hz),
160.13(d,J=8.1Hz),152.26,150.06,149.13,145.21,142.66,131.73,130.66(d,J=
10.1Hz),120.13,118.00,115.73(d,J=16.2Hz),113.85,112.01(d,J=6.1Hz),111.82(d,
J=6.1Hz),100.22,72.93(t,J=3.0Hz),65.51,63.71,49.16,44.78,42.14,41.55,40.22,
+
32.49,31.77.HRMS计算值C28H26F2N6O4S[M+H]581.17771.实测值581.17399.
烷萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓缩,并进一步以硅胶柱层析纯化,得到
式(3‑13)所示的化合物。
4.8Hz,1H),6.85(t,J=8.4Hz,2H),6.01(dd,J=11.6,9.6Hz,1H),5.66(d,J=48.0Hz,2H),
5.38(s,2H),4.53(d,J=13.6Hz,1H),3.99(d,J=12.4Hz,1H),3.74(dd,J=17.2,12.0Hz,
1H),3.56(dd,J=17.2,9.0Hz,1H),3.33–3.22(m,2H),2.80(t,J=11.6Hz,1H),2.25–2.05
13
(m,2H),1.87–1.67(m,2H). C NMR(150MHz,CDCl3)δ174.22,164.57,161.92,160.28,
152.06,151.35,149.08,144.86,139.83(t,J=14.2Hz),130.46(t,J=7.1Hz),129.74,
117.90,117.37,115.48(t,J=11.1Hz),114.37,111.75,111.60,78.20,72.63,48.24,
+
44.41,41.74,41.29,40.02,32.24,31.58.HRMS计算值C26H23F3N6O2S[M+H] 541.16281.实测
值541.16508.
烷萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓缩,并进一步以硅胶柱层析纯化,得到
式(3‑14)所示的化合物。
4.8Hz,1H),6.94(t,J=54.0Hz,1H),6.90(t,J=8.4Hz,2H),6.07(dd,J=12.0,9.0Hz,1H),
5.43(s,2H),4.57(d,J=13.8Hz,1H),4.04(d,J=13.8Hz,1H),3.79(dd,J=17.4,12.0Hz,
1H),3.62(dd,J=17.4,9.0Hz,1H),3.37–3.28(m,2H),2.88(t,J=12.6Hz,1H),2.25(d,J=
13
13.8Hz,1H),2.16(d,J=10.8Hz,1H),1.93–1.85(m,1H),1.85–1.73(m,1H). C NMR
(150MHz,CDCl3)δ174.18,164.44,162.29,160.63,152.32,151.47,149.91,145.31,138.43
(t,J=30.2Hz),130.62(t,J=7.1Hz),130.41,118.37,117.81,115.83(t,J=10.1Hz),
112.50,112.19,112.01,111.86,72.94,48.67,44.75,42.07,41.62,40.30,32.54,
+
31.83.HRMS计算值C26H22F4N6O2S[M+H]559.17858.实测值559.17683.
1h,然后再加入四丁基氟化铵(3mL,3.00mmol,3eq,1M四氢呋喃溶液),继续搅拌反应30min,
反应完毕,加入60mL水,以乙酸乙酯萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓缩,
并进一步以硅胶柱层析纯化,得到式(3‑16)所示的化合物。
6.91(t,J=8.4Hz,2H),6.07(t,J=10.8Hz,1H),5.43(s,2H),4.58(d,J=13.8Hz,1H),4.05
(d,J=13.8Hz,1H),3.95–3.70(m,3H),3.63(dd,J=17.4,9.0Hz,1H),3.33(t,J=12.6Hz,
2H),2.87(t,J=12.6Hz,1H),2.24(d,J=13.2Hz,1H),2.15(d,J=13.2Hz,1H),1.90–1.75
13
(m,2H). C NMR(150MHz,CDCl3)δ174.35,164.92,162.32(d,J=6.1Hz),160.66(d,J=
6.1Hz),152.38,151.66,149.36,145.31,134.90,130.66(t,J=10.6Hz),130.07,125.37
(q,J=277.8Hz),117.84,117.53,115.88(t,J=16.2Hz),115.22,112.06,111.89,72.99,
48.58,44.78,42.11,41.68,40.38,33.74(d,J=31.7Hz),32.57,31.90.HRMS计算值
+
C27H23F5N6O2S[M+H]591.15961.实测值591.15960.
2h,反应完毕,加入60mL水,以乙酸乙酯萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓
缩,并进一步以硅胶柱层析纯化,得到式(3‑21)所示的化合物。
8.4,4.8Hz,1H),7.15(t,J=8.4Hz,2H),6.23(d,J=28.8Hz,1H),6.02(dd,J=12.6,9.0Hz,
1H),5.57(d,J=17.2Hz,1H),5.48(d,J=17.2Hz,1H),4.34(d,J=13.2Hz,1H),4.14(d,J=
13.2Hz,1H),3.91(dd,J=17.2,12.0Hz,1H),3.57–3.53(m,1H),3.39(t,J=11.6Hz,1H),
3.32(t,J=12.6Hz,1H),2.81(t,J=12.6Hz,1H),2.11(dd,J=39.0,13.2Hz,2H),1.84(q,J
13
=12.6Hz,1H),1.56(q,J=12.6,1H). C NMR(100MHz,DMSO‑d6)δ175.06,164.82,162.01
(d,J=8.1Hz),159.53(d,J=8.1Hz),152.22,151.00,149.19,144.41,133.77(d,J=
6.1Hz),133.67(d,J=6.1Hz),131.46(t,J=10.1Hz),130.15(d,J=6.1Hz),120.02,
117.25,115.70(t,J=16.2Hz),113.58(d,J=3.0Hz),112.37(d,J=6.1Hz),112.18(d,J=
6.1Hz),75.11(d,J=14.2Hz),74.78(d,J=14.2Hz),72.14(t,J=3.0Hz),48.46,44.00,
+
41.28(d,J=6.1Hz),32.34,31.88.HRMS计算值C27H22F4N6O2S[M+H] 571.15338.实测值
571.15289.
锂(1.5mL,1.5eq,1M四氢呋喃溶液),升至室温,继续反应2h,反应完毕,加入10mL饱和氯化
铵淬灭和10mL水,以乙酸乙酯萃取,有机相以饱和食盐水洗涤,硫酸钠干燥后,浓缩,并进一
步以硅胶柱层析纯化,得到式(3‑22)所示的化合物。
1H),6.92(t,J=8.4Hz,2H),6.74–6.56(m,1H),6.15–5.96(m,2H),5.41(d,J=19.2Hz,2H),
4.61(d,J=12.4Hz,1H),4.07(t,J=12.0Hz,1H),3.81(dd,J=16.8,12.0Hz,1H),3.64(dd,
J=17.2,9.2Hz,1H),3.32(t,J=11.2Hz,2H),2.87(t,J=11.6Hz,1H),2.27–2.15(m,2H),
13
2.15–2.10(m,2H),1.97(d,J=6.0Hz,1H),1.90–1.75(m,2H). C NMR(100MHz,CDCl3)δ
174.45,165.05,165.03,162.68(d,J=8.1Hz),160.18(d,J=8.1Hz),152.34,148.43,
145.22,142.20,131.52,130.63(t,J=10.1Hz),123.12,118.25,117.84,116.94,116.70,
115.83(t,J=16.2Hz),112.03(t,J=6.1Hz),111.84(t,J=6.1Hz),72.93(t,J=3.0Hz),
+
48.90,44.80,42.05,41.63,40.42,32.57,31.91,19.07.HRMS计算值C28H26F2N6O2S[M+H]
549.18788.实测值549.18675.
10mL乙酸乙酯,依次以20mL水和饱和食盐水洗涤,硫酸钠干燥后,浓缩,并进一步以硅胶柱
层析纯化,得到式(3‑24)所示的化合物。
7.8Hz,2H),6.13–6.05(m,1H),5.43(s,2H),4.59(d,J=14.4Hz,1H),4.04(d,J=13.2Hz,
1H),3.87–3.77(dd,J=17.2,13.2Hz,1H),3.64(dd,J=17.2,9.0Hz,1H),3.34(t,J=
12.0Hz,2H),2.87(t,J=12.0Hz,1H),2.27(d,J=15.6Hz,1H),2.17(d,J=14.4Hz,1H),
13
1.90–1.78(m,2H). C NMR(100MHz,DMSO‑d6)δ175.43,164.49,161.95(d,J=8.1Hz),
159.47(d,J=8.1Hz),152.26,150.06,149.63,144.10,131.48(t,J=10.1Hz),129.47,
126.91,120.34,118.29,116.63,115.55(t,J=16.2Hz),112.34(d,J=5.1Hz),112.16(d,J
=6.1Hz),84.12,72.27,48.72,43.99,41.29,41.01,32.30,31.81,23.73.HRMS计算值
+
C27H21F2IN6O2S[M+H]659.05322.实测值659.04904.
体系经过滤,浓缩得到式(3‑26)所示的化合物。
6.98(s,1H),6.01(t,J=10.8Hz,1H),5.70(s,2H),5.20–5.00(m,2H),4.33(d,J=13.2Hz,
1H),4.10(d,J=13.2Hz,1H),3.90(t,J=15.0Hz,1H),3.54(dd,J=17.2,8.6Hz,1H),3.35–
3.20(m,2H),2.78(t,J=13.2Hz,1H),2.08(t,J=13.8Hz,2H),1.76–1.65(m,1H),1.57–
13
1.48(m,1H). C NMR(100MHz,DMSO‑d6)δ175.17,165.68,162.03(d,J=7.1Hz),159.54(d,J
=7.1Hz),152.25,151.49,148.52,147.67,144.39,131.53(t,J=10.1Hz),130.03,
120.09,115.73(t,J=16.2Hz),114.08,112.42(d,J=5.1Hz),112.23(d,J=5.1Hz),
+
107.27,72.14,47.42,44.05,41.28,32.44,31.95.HRMS计算值C25H23F2N7O2S[M+H]
524.16748.实测值524.16795.
式(3‑29)所示化合物在给药浓度为20mg/L时,对黄瓜霜霉病的防效均在A级,达到90%以
上。
把菌丝体捣碎成小菌丝段,制成菌丝段悬浮液,置于4℃下备用。
5
放。待游动孢子充分释放后,配置孢子浓度为10个孢子/mL的孢子悬浮液,置于4℃下备用。
3‑4天(致病疫霉7天)后用酶标仪检测各处理的OD595(595nm处的吸光值)值。计算药剂对靶
标菌的室内毒力。测试结果如表2所示。
大的开发潜力。
(3‑20)、式(3‑25)、式(3‑28)等5个所示化合物对辣椒疫霉的菌丝生长抑制作用为A级,抑制
率大于95%;式(3‑1)、式(3‑3)、式(3‑4)、式(3‑12)、式(3‑13)、式(3‑15)、式(3‑16)、式(3‑
19)、式(3‑20)、式(3‑25)、式(3‑28)和式(3‑29)等所示的12个化合物对致病疫霉的菌丝生
长抑制作用为C级及以上,大于85%的抑制率;式(3‑1)、式(3‑3)、式(3‑4)、式(3‑12)、式(3‑
13)、式(3‑14)、式(3‑16)、式(3‑19)、式(3‑20)和式(3‑28)等所示的10化合物对荔枝霜疫霉
的菌丝生长抑制作用为C级及以上,大于85%的抑制率。
它的合适方式进行组合,这些简单变型和组合同样应当视为本发明所公开的内容,均属于
本发明的保护范围。