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第 6 期 林 艳，等: 1-氯甲基磺酰胺类化合物的合成 ·1259·

是产率偏低（42%）；当采用位阻较大的二苯胺时， potential[J]. Bioorg Med Chem, 2015, 23(13): 3059-3080.
未监测到目标产物的生成，一方面可能因为二苯胺 [6] Srivastava N, Kumar A. Synthesis and study of 1-ethyl-3-
位阻较大，另一方面可能由于二苯胺为仲胺，氨基 carbohydrazide and 3-[1-oxo-2-hydrazino-3-{p-toluenesulfon}quinolone
derivatives against bacterial infections[J]. Eur J Med Chem, 2013,
碱性较弱的缘故。
67: 464-468.
2.3 1-氯-N-（4-甲氧基苯基）甲磺酰胺（üg）的 [7] Lal J, Gupta S K, Thavaselvam D, et al. Biological activity, design,
结构解析 synthesis and structure activity relationship of some novel derivatives
1
从化合物Ⅲg 的 HNMR 解析中可以看出，δ of curcumin containing sulfonamides[J]. Eur J Med Chem, 2013, 64:
7.28 的两组三重峰为苯环氨基邻位上的 H，δ 6.92 579-588.
[8] Nagarajan S R, De Crescenzo G A, Getman D P, et al. Discovery of
的两组三重峰为苯环甲氧基邻位上的 H，δ 6.83 的
novel benzothiazolesulfonamides as potent inhibitors of HIV-1
宽峰为磺酰胺上 N—H 的 H 峰，δ 4.45 和 3.83 的单 protease[J]. Bioorg Med Chem, 2003, 11(22): 4769-4777.
峰分别为—CH 2 —和—OCH 3 的 H 峰，其中—CH 2 — [9] Benmansour F, Trist I, Coutard B, et al. Discovery of novel dengue
由于氯原子和磺酰基共同的吸电子作用，其化学位 virus NS5 methyltransferase non-nucleoside inhibitors by fragment-
13
移显著增加。在 CNMR 解析中，δ 158.8、127.4、 based drug design[J]. Eur J Med Chem, 2016, 125: 865-880.
[10] Patel D, Jain M, Shah S R, et al. Discovery of potent, selective and
126.2、114.9 分别对应苯环上的 6 个 C，其中 δ 158.8
orally bioavailable triaryl-sulfonamide based PTP1B inhibitors[J].
为苯环上与甲氧基直接相连的 C，而 δ 127.4 为苯环 Bioorg Med Chem Lett, 2012, 22(2): 1111-1117.
上与氨基直接相连的 C，由于氨基邻位的两个碳、 [11] Frkic R L, He Y H, Rodriguez B B, et al. Structure-activity
甲氧基邻位的两个碳化学环境相同，故苯环 6 个碳 relationship of 2, 4-dichloro- N-(3,5-dichloro-4-(quinolin-3-yloxy)phenyl)
benzenesulfonamide(INT131) analogs for PPAR γ-targeted
在碳谱中只出现了 4 个峰。δ 55.6 和 52.7 分别为甲
antidiabetics[J]. J Med Chem, 2017, 60(11): 4584-4593.
氧基和亚甲基上的 C 峰。
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inhibitors: Inhibition of plasmodium falciparum carbonic anhydrase
3 结论 with aromatic/heterocyclic sulfonamides–in vitro and in vivo
studies[J]. Bioorg Med Chem Lett, 2008, 18(20): 5466-5471.
在 0 ℃至室温条件下，以吡啶为催化剂，实现
[13] Salahuddin A, Inam A, van Zyl R L, et al. Synthesis and evaluation
了氯甲基磺酰氯与取代芳香伯胺和苄胺的磺酰化反 of 7-chloro-4-(piperazin -1-yl)quinoline-sulfonamide as hybrid
应，合成了 9 个芳环上具有不同取代基的磺酰胺类 antiprotozoal agents[J]. Bioorg Med Chem, 2013, 21(11): 3080-
化合物，产率最高可达 95%。考察了不同催化剂、 3089.
[14] Wimum J Y, Dogn J M, Casin I A, et al. Carbonic anhydrase
溶剂、温度和物料比对磺酰化反应的影响，确定了
inhibitors: Synthesis andinhibition of cytosolic/membrane–associated
最优反应条件，通过不同胺的扩展实验验证了该反 carbonic anhydrase isozymes Ⅰ, Ⅱ, and Ⅸ with sulfonamides
应的底物适用性。该合成方法具有反应条件温和， incorporating hydrazino moieties[J]. J Med Chem, 2005, 48(6):
产率较高，底物适用范围较广等优点，为磺酰胺类 2121-2125.
化合物的合成提供了理论依据。此外，在磺酰胺的 [15] Sun L, Wu Y, Liu Y, et al. Novel carbazole sulfonamide derivatives
of antitumor agent: Synthesis, antiproliferative activity and aqueous
基础上进行衍生化研究，以 90%的产率合成了一种
solubility[J]. Bioorg Med Chem Lett, 2016, 27(2): 261-265.
磺酰亚胺——N-苄基-1-氯-N-（3-氯苯基）甲磺酰 [16] Chandak N, Ceruso M, Supuran C T, et al. Novel sulfonamide
亚胺。 bearing coumarin scaffolds as selective inhibitors of tumor associated
carbonic anhydrase isoforms Ⅸ and Ⅻ[J]. Bioorg Med Chem,
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