新型含吡唑基[1,2,4]噁二唑-[5,4-d][1,5]苯并硫氮杂卓衍生物的合成与表征

方庆华,费婷虹,周英雷,刘方明

(1. 杭州师范大学健康管理学院,浙江 杭州 310036;2. 杭州师范大学材料与化学化工学院，浙江 杭州 310036)

新型含吡唑基[1,2,4]噁二唑-[5,4-d][1,5]苯并硫氮杂卓衍生物的合成与表征

方庆华1,费婷虹2,周英雷2,刘方明2

(1. 杭州师范大学健康管理学院,浙江 杭州 310036;2. 杭州师范大学材料与化学化工学院，浙江 杭州 310036)

以[1,5]苯并硫氮杂卓衍生物1a-l和含吡唑基的氯代肟4为起始原料，通过1,3-偶极环加成的方法合成了一系列新型含吡唑基[1,2,4]噁二唑-[5,4-d][1,5]苯并硫氮杂卓衍生物.并通过元素分析、1H NMR，MS，IR对这类化合物进行了表征.

[1,5]苯并硫氮杂卓;1,3-偶极环加成;[1,2,4]噁二唑;吡唑

1,5-苯并硫氮杂卓是一类具有广谱活性的七元杂环化合物，具有很好的抗高血压[1]、抗抑郁[2]、抗凝血[3]、抗动脉硬化[4]、抗-HIV[5]、杀菌[6]等作用，近几十年来引起许多化学家的广泛关注，其中许多含有1,5-苯并硫氮杂卓杂环的药物已被用于临床.例如正在使用的药物地尔硫卓被作为钙通道阻断剂[7]、钙离子通道拮抗剂[8]、抗惊厥剂和安神剂[9].五元杂环吡唑及其衍生物也表现出广泛的药理活性，如抗高血糖[10-11]、抗细菌[12]、抗抑郁[13]、抗炎[14]和抗肿瘤[15].此外，[1,2,4]噁二唑也是一类具有各种药理活性的五元环[16].

在[1,5]苯并硫氮杂卓上引入其他的杂环将大大提高其药理活性[17-19]，此外，在[1,5]苯并硫氮杂卓环的2位或4位引入一个杂环，将产生比母体分子更多的活性[20].据此，笔者设计并通过1,3-偶极环合加成的方法合成了一系列新型的三环稠环化合物，其有望表现出更好的药理活性.合成路线如图1所示.

图1 目标产物的合成路线Fig. 1 The synthetic route of the target product

1 实验部分

1.1 仪器与试剂

合成所用的试剂均为分析纯或化学纯.北京泰克X-5显微熔点仪(温度计未校正)，Bruker Tensor27红外光谱仪(KBr)，Agilent-5975质谱仪，Varian Mercury-Plus400型核磁共振仪(内标TMS，溶剂为CDCl3)，Perkin-Elmer2400 CHN元素分析仪.2,4-二芳基-1,5-苯并硫氮杂卓1a-l的合成参照文献[21]，1-苯基-3-甲基-5-苯氧基-4-吡唑甲醛2 的合成参照文献[22].

1.2 1-苯基-3-甲基-5-苯氧基-吡唑甲醛肟3的合成

取20.0 mmol 1-苯基-3-甲基-5-苯氧基-4-吡唑甲醛2溶于50.0 mL乙醇中，室温搅拌下滴加316.0 mg盐酸羟胺和464.0 mg醋酸钠的水溶液.有大量固体析出后，再加热回流10 min.静置过夜，抽滤，水洗，所得固体用乙醇/水重结晶，得到产物3.

1.3 α-1-苯基-3-甲基-5-苯氧基-4-吡唑甲醛肟4的合成

取10.0 mmol1-苯基-3-甲基-5-苯氧基-4-吡唑甲醛肟3溶于12.5 mL DMF中，分次缓慢加入15.0 mmol NCS，反应控制在35 ℃以下，直到反应液可以使湿润的淀粉碘化钾试纸无色或弱色为止，将反应液倒入80.0 mL水中，用乙醚萃取2次，将萃取液用水洗3次，无水Na2SO4干燥，旋干，氯仿/石油醚重结晶，得到化合物4.浅黄色晶体.产率(%)：86，熔点：146～148 ℃; MS(EI)m/z(%)：327(M+)，291，274，143，77(100)，51.

1.4 3a,5-二芳基-1-(1-苯基-3-甲基-5-苯氧基-吡唑-4-基)-3a,4,5,11-4H-[1,2,4]噁二唑[5,4-d]1,5-苯并硫氮杂卓的合成3a-1

将2,4-二芳基-1,5-苯并硫氮杂卓(1.0 mmol)、吡唑甲醛氯肟(2.0 mmol)溶于干燥的二氯甲烷中，在室温搅拌下滴加新蒸的三乙胺(2.0 mmol)，继续搅拌48 h，TLC检测，反应结束后滤去铵盐，减压浓缩，用V(乙酸乙酯)∶V(石油醚)=1∶8柱层析得到淡黄色或白色固体.

3a:浅黄色晶体; 产率(%): 23.1; m.p.: 192～194 ℃; IR(KBr)ν/cm-1: 3 076(Ar—H),1 635(C=N), 1 479(C=C), 1 357(C—N), 763(C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.72～6.43(m, 24H, Ar—H), 3.20 (dd, 1H, H5x,Jax=5.52 Hz,Jbx=10.32 Hz), 2.63 (dd, 1H, H4a,Jax=5.52 Hz,Jab=13.08 Hz), 2.55 (s, 3H, —CH3), 2.42 (dd, 1H, H4b,Jbx=10.32 Hz,Jab=13.08 Hz); MS(EI)m/z(%): 606 (M+), 502, 409, 304, 211, 105(100); Anal. calcd for C38H30N4O2S: C 75.22, H 4.98, N 9.23 ; Found: C 75.11, H 5.03, N 9.19.

3b: 浅黄色晶体; 产率(%): 25.5; m.p.: 241～243 ℃; IR(KBr)ν/cm-1: 3 058 (Ar—H), 1 634 (C=N), 1 479 (C=C), 1 355 (C—N), 764 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.68～6.51 (m, 23H, Ar—H), 3.30 (dd, 1H, H5x,Jax=5.64 Hz,Jbx=10.40 Hz), 2.69 (dd, 1H, H4a,Jax=5.64 Hz,Jab=13.12 Hz), 2.57 (s, 3H, -CH3), 2.48 (dd, 1H, H4b,Jbx=10.40 Hz,Jab=13.12 Hz); MS(EI)m/z(%): 640 (M+), 502, 409, 304, 211, 105(100); Anal. calcd for C38H29ClN4O2S: C 71.18, H 4.56, N 8.74 ; Found: C 71.13, H 4.61, N 8.69.

3c: 浅黄色晶体; 产率(%): 31.0; m.p.: 209～210 ℃; IR(KBr)ν/cm-1: 3 059 (Ar—H), 1 635 (C=N), 1 487 (C=C), 1 349 (C—N), 762 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.67～6.63 (m, 23H, Ar—H), 3.80 (s,3H,-OCH3), 3.27 (dd, 1H, H5x,Jax=5.48 Hz,Jbx=10.36 Hz), 2.67 (dd, 1H, H4a,Jax=5.48 Hz,Jab=13.08 Hz), 2.56 (s, 3H, -CH3), 2.48 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.08 Hz); MS(EI)m/z(%): 636 (M+), 502, 409, 304, 211, 105(100); Anal. calcd for C39H32N4O3S: C 73.56, H 5.07, N 8.80 ; Found: C 73.55, H 5.12, N 8.76.

3d: 浅黄色晶体; 产率(%): 27.3; m.p.: 172～174 ℃; IR(KBr)ν/cm-1: 3 055 (Ar—H), 1 631 (C=N), 1 480 (C=C), 1 347 (C—N), 763 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.69～6.58 (m, 23H, Ar—H), 3.27 (dd, 1H, H5x,Jax=5.44 Hz,Jbx=10.36 Hz), 2.68 (dd, 1H, H4a,Jax=5.44 Hz,Jab=13.16 Hz), 2.58 (s, 3H, -CH3), 2.47 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.16 Hz); MS(EI)m/z(%): 651 (M+), 502, 409, 304, 211, 105(100); Anal. calcd for C38H29N5O4S: C 70.03, H 4.49, N 10.75 ; Found: C 69.98, H 4.53, N 10.74.

3e: 浅黄色晶体; 产率(%): 22.2; m.p.: 250～251 ℃; IR(KBr)ν/cm-1: 3 038 (Ar—H), 1 634 (C=N), 1 488 (C=C), 1 342 (C—N), 762 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.68～6.56 (m, 23H, Ar—H), 3.34 (dd, 1H, H5x,Jax=5.52 Hz,Jbx=10.28 Hz), 2.72 (dd, 1H, H4a,Jax=5.52 Hz,Jab=13.12 Hz), 2.57 (s, 3H, -CH3), 2.45 (dd, 1H, H4b,Jbx=10.28 Hz,Jab=13.12 Hz); MS(EI)m/z(%): 640 (M+), 536, 443, 304, 245, 139(100); Anal. calcd for C38H29ClN4O2S: C 71.18, H 4.56, N 8.74 ; Found: C 71.17, H 4.61, N 8.68.

3f: 浅黄色晶体; 产率(%): 24.1; m.p.: 196～198 ℃; IR(KBr)ν/cm-1: 3 039 (Ar—H), 1 631 (C=N), 1 482 (C=C), 1 337 (C—N), 763 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.63～6.55 (m, 22H, Ar—H), 3.29 (dd, 1H, H5x,Jax=5.60 Hz,Jbx=10.36 Hz), 2.71 (dd, 1H, H4a,Jax=5.60 Hz,Jab=13.20 Hz), 2.57 (s, 3H, -CH3), 2.44 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.20 Hz); MS(EI)m/z(%): 674 (M+), 536, 443, 304, 245, 139(100); Anal. calcd for C38H28Cl2N4O2S: C 67.55, H 4.18, N 8.29 ; Found: C 67.49, H 4.25, N 8.28.

3g: 浅黄色晶体; 产率(%): 30.4; m.p.: 181～183 ℃; IR(KBr)ν/cm-1: 3 033 (Ar—H), 1 640 (C=N), 1 481 (C=C), 1 352 (C—N), 761 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.64～6.57 (m, 22H, Ar—H), 3.81 (s,3H,-OCH3), 3.30 (dd, 1H, H5x,Jax=5.56 Hz,Jbx=10.36 Hz), 2.71 (dd, 1H, H4a,Jax=5.56 Hz,Jab=13.16 Hz), 2.57 (s, 3H, -CH3), 2.44 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.16 Hz); MS(EI)m/z(%): 670 (M+), 536, 443, 304, 245, 139(100); Anal. calcd for C39H31ClN4O3S: C 69.79, H 4.66, N 8.35 ; Found: C 69.77, H 4.69, N 8.37.

3h: 浅黄色晶体; 产率(%): 28.0; m.p.: 241～244 ℃; IR(KBr)ν/cm-1: 3 041 (Ar—H), 1 643 (C=N), 1 488 (C=C), 1 353 (C—N), 764 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.63～6.56 (m, 22H, Ar—H), 3.29 (dd, 1H, H5x,Jax=5.64 Hz,Jbx=10.40 Hz), 2.68 (dd, 1H, H4a,Jax=5.64 Hz,Jab=13.24 Hz), 2.58 (s, 3H, -CH3), 2.43 (dd, 1H, H4b,Jbx=10.40 Hz,Jab=13.24 Hz); MS(EI)m/z(%): 685 (M+), 536, 443, 304, 245, 139(100); Anal. calcd for C38H28ClN5O4S: C 66.51, H 4.11, N 10.21 ; Found: C 66.51, H 4.13, N 10.22.

3i: 浅黄色晶体; 产率(%): 29.7; m.p.: 212～216 ℃; IR(KBr)ν/cm-1: 3 029 (Ar—H), 1 647 (C=N), 1 477 (C=C), 1 342 (C—N), 761 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.62～6.57 (m, 23H, Ar—H), 3.79 (s,3H,-OCH3), 3.35 (dd, 1H, H5x,Jax=5.52 Hz,Jbx=10.28 Hz), 2.68 (dd, 1H, H4a,Jax=5.52 Hz,Jab=13.12 Hz), 2.57 (s, 3H, -CH3), 2.43 (dd, 1H, H4b,Jbx=10.28 Hz,Jab=13.12 Hz); MS(EI)m/z(%): 636 (M+), 532, 439, 306, 241, 135(100); Anal. calcd for C39H32N4O3S: C 73.56, H 5.07, N 8.80 ; Found: C 73.55, H 5.06, N 8.83.

3j: 浅黄色晶体; 产率(%): 28.5; m.p.: 182～184 ℃; IR(KBr)ν/cm-1: 3 031 (Ar—H), 1 650 (C=N), 1 483 (C=C), 1 350 (C—N), 761 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.64～6.58 (m, 22H, Ar—H), 3.78 (s,3H,-OCH3), 3.31 (dd, 1H, H5x,Jax=5.60 Hz,Jbx=10.36 Hz), 2.70 (dd, 1H, H4a,Jax=5.60 Hz,Jab=13.16 Hz), 2.58 (s, 3H, -CH3), 2.45 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.16 Hz); MS(EI)m/z(%): 670 (M+), 532, 439, 306, 241, 135(100); Anal. calcd for C39H31ClN4O3S: C 69.79, H 4.66, N 8.35 ; Found: C 69.77, H 4.63, N 8.37.

3k:浅黄色晶体; 产率(%): 30.2; m.p.: 172～174 ℃; IR(KBr)ν/cm-1: 3 035 (Ar—H), 1 633 (C=N), 1 478 (C=C), 1 337 (C—N), 761 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.63～6.57 (m, 22H, Ar—H), 3.79 (s,3H,-OCH3), 3.73 (s,3H,-OCH3), 3.35 (dd, 1H, H5x,Jax= 5.64 Hz,Jbx= 10.20 Hz), 2.72 (dd, 1H, H4a,Jax=5.64 Hz,Jab=13.12 Hz), 2.57 (s, 3H, -CH3), 2.43 (dd, 1H, H4b,Jbx=10.20 Hz,Jab=13.12 Hz); MS(EI)m/z(%): 666 (M+), 532, 439, 306, 241, 135(100); Anal. calcd for C40H34N4O4S: C 72.05, H 5.14, N 8.40 ; Found: C 72.09, H 5.17, N 8.39.

3l: 浅黄色晶体; 产率(%): 33.5; m.p.: 225～227 ℃; IR(KBr)ν/cm-1: 3 032 (Ar—H), 1 635 (C=N), 1 481 (C=C), 1 332 (C—N), 764 (C—S—C);1H NMR (CDCl3, 400 MHz)δ: 7.64～6.55 (m, 22H, Ar—H), 3.80 (s,3H,-OCH3), 3.29 (dd, 1H, H5x,Jax=5.60 Hz,Jbx=10.36 Hz), 2.70 (dd, 1H, H4a,Jax=5.60 Hz,Jab=13.16 Hz), 2.58 (s, 3H, -CH3), 2.43 (dd, 1H, H4b,Jbx=10.36 Hz,Jab=13.16 Hz); MS(EI)m/z(%): 681 (M+), 532, 439, 306, 241, 135(100); Anal. Calcd for C39H31N5O5S: C 68.71, H 4.58, N 10.27 ; Found: C 68.68, H 4.59, N 10.27.

2 结果与讨论

2.1 化合物的合成

根据文献 [21]，α,β-不饱和酮(查尔酮)是由芳香醛和苯乙酮通过Claisen-Schmidt缩合反应得到的，查尔酮与和等量的邻氨基硫酚在酸化的乙醇中回流得到起始原料[1,5]苯并硫杂卓衍生物1a-l.

在合成1a-l的的过程中，反应分两步进行:第一步,由于—SH的亲核性大于—NH2，邻氨基硫酚中的—SH负电子进攻查尔酮类似物共轭双键中得β碳原子发生1,4-迈克尔加成;第二步,—NH2与C=O脱水缩合得到[1,5]苯并硫氮杂卓衍生物1a-l.

[1,5]苯并硫氮杂卓衍生物1a-1是以二氯甲烷为溶剂在室温下搅拌48 h以上得到的，但是吡唑甲醛氯肟4和三乙胺都应稍微过量.最终产物的结构是由IR，1H NMR，MS和元素分析确证的.

2.2 目标化合物的谱图表征

IR：最终产物3a-l在1 650～1 631 cm-1、1 488～1 477cm-1及764～761 cm-1范围内分别出现了C=N，C=C和C—S—C的振动吸收峰.在3 076～3 029 cm-1范围内表现出Ar—H伸缩振动吸收峰.

1HNMR：最终产物3a-l在δ:7.72～6.43 ppm处出现的多重峰为芳环上的氢质子峰，在δ:2.58～2.55 ppm处出现的单峰为甲基上的氢质子峰，杂卓七元环上的3个饱和氢质子Hx、Hb、Ha出现在δ:3.33～2.37 ppm.例如在化合物3c中，在δ:3.78 ppm和δ:2.58 ppm处出现的单峰分别为甲氧基和甲基上的氢质子峰.杂卓七元环上的3个饱和氢质子中的Hx在δ:3.27处出现三重峰，杂卓七元环上的3个饱和氢质子中的Ha和Hb分别在δ:2.67和δ:2.48处出现双重峰，这样的分裂是由于卓环3位上的两个不等价的氢质子邻位耦合造成的.同时在δ:7.67～6.63 ppm处出现芳环上氢质子的多重峰.

MS： 此类化合物的分子离子峰都相对较弱，以化合物3e为例，MS(EI)m/z(%): 640 (M+), 536, 443, 304, 245, 139(100).

[1] Levai A. Optically active 1,5-benzothiazepines[J]. Pharmazie,1999,54(10):719-726.

[2] Darias V, Sanchez-Mateo C C. Exposito-Orta M A,etal. New thieno and pyrazolo[2,1]benzothiazepine derivatives with antidepressant activity[J]. Pharmazie,1999,54(10):783-784.

[3] Weiss K, Fitscha P, Gazso A. Calcium blockers: antiatherogenic action by influencing the prostaglandin-system[J]. Prog Clin Biol Res,1989,301:353-357.

[4]Etingin O R， Hajjar D P. Calcium channel blockers enhance cholesteryl ester hydrolysis and decrease total cholesterol accumulation in human aortic tissue[J]. Circ Res,1990,66(1):185-190.

[5] Grandolimi G, Perioli L, Ambrogi V. Synthesis of some new 1,4-benzothiazine and 1,5-benzothiazepine tricyclic derivatives with structural analogy with TIBO and their screening for anti-HIV activity[J]. Eur J Med Chem,1999,34(9):701-709.

[6] Naik V R, Naik H B. Synthesis and antibacterial activity of 2,3-dihydro-4-(2′-hydroxy-3′-bromo-5′-ethylphen-1′-yl)-2-substitutedphenyl-1,5-benzothiazepine derivatives[J]. Asian J Chem,1999,11(2):661-662.

[7] Chaffman M, Brogden R N. Diltiazem: A review of its pharmacological properties and therapeutic efficacy[J]. Drugs,1985,29(5):387-454.

[8] Itoh K, Kori M, Indada Y,etal. Synthesis and angiotensin converting enzyme inhibitory activity of 1,5-benzothiazepine and 1,5-benzoxazepine derivatives. II[J]. Chem Pharm Bull,1986,34(5):2078-2089.

[9] Bock M G, Dipardo R M, Evans B E,etal. Benzodiazepine gastrin and brain cholecystokinin receptor ligands: L-365, 260[J]. J Med Chem,1989,32(1):13-16.

[10] Iijima I, Ozeki M, Okumura K,etal. Benzoxazole derivatives and preparation thereof: EP 283035[P].1988-09-21.

[11] Clark A D, Goldstein St W，Hulin B. Thiazolidinedione derivatives as hypoglycemic agents: EP 389699[P].1990-10-03.

[12] Genin M J, Biles C, Keiser B J,etal. Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: lead identification and SAR of 3- and 4-substituted derivatives[J]. J Med Chem,2000,43(5):1034-1040.

[13] Bailey D M, Hansen P E, Hlavac A G,etal. 3,4-Diphenyl-1H-pyrazole-1-propanamine antidepressants[J]. J Med Chem,1985,28(2):256-260.

[14] Szabo G, Fischer J, Kis-Varga A,etal. New celecoxib derivatives as anti-inflammatory agents[J]. J Med Chem,2008,51(1):142-147.

[15] Farag A M, Mayhoub A S, Barakat S E,etal. Regioselective synthesis and antitumor screening of some novel N-phenylpyrazole derivatives[J]. Bioorg Med Chem,2008,16(2):881-889.

[16] Srivastava R M, de Almeida Lima A, Viana O S,etal. Antiinflammatory property of 3-aryl-5-(n-propyl)-1,2,4-oxadiazoles and antimicrobial property of 3-aryl-5-(n-propyl)-4,5-dihydro-1,2,4-oxadiazoles: their syntheses and spectroscopic studies[J]. Bioorg Med Chem,2003,11(8):1821-1827.

[17] Ambrogi V, Grandolini G, Perioli L,etal. Studies on annulated 1,4-benzothiazines and l,5-benzothiazepines. IX. Imidazo[2,1-d][1,5]benzothiazepines: synthesis and in vitro benzodiazepine receptor affinity[J]. Eur J Med Chem,1995,30(5):429-437.

[18] Sarro G D, Chimirri A, Sarro A D,etal. 5H-[1,2,4]Oxadiazolo[5,4-d][1,5]benzothiazepines as anticonvulsant agents in DBA/2 mice[J]. Eur J Med Chem,1995,30(12):925-929.

[19] Ambrogi V, Giampietri A, Grandolini G,etal. Studies on annelated [1,4]benzothiazines and [1,5]benzothiazepines, V. Synthesis and biological activity of N-2 alkylamino derivatives of 4,5-dihydro-s-triazolo[3,4-d]-1,5-benzothiazepine[J]. Arc Pharm,1992,325(9):569-577.

[20] Mane R A, Ingle D B. Synthesis and biological activity of some new 1,5-benzothiazepines containing thiazole moiety: 2-aryl-4-(4-methyl-2-substituted-aminothiazol-5-yl)-2,3-dihydro-1,5-benzothiazepines[J]. Indian J Chem, Sect B,1982，21B:973-974.

[21] Stephens W D, Field L. A seven-membered heterocycle fromo-aminobenzenethiol and chalcone[J]. J Org Chem,1959,24(10):1576.

[22] 李在国.有机中间体制备[M].2版.北京:化学工业出版社,2000:147-154.

SynthesisandCharacterizationofNovel[1,2,4]Oxadiazolo-[5,4-d][1,5]benzothiazepineDerivativesContainingPyrazoleMoietyby1,3-DipolarCycloaddition

FANG Qinghua1, FEI Tinghong2, ZHOU Yinglei2, LIU Fangming2

(1. School of Health Management, Hangzhou Normal University, Hangzhou 310036, China;2. College of Materials，Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou 310036, China)

A series of new substituted-[1,2,4]oxadiazolo-[5,4-d][1,5]benzothiazepine derivatives containing a pyrazole ring 3a-lwere synthesized from substituted-[1,5]benzothiazepines 1a-land pyrazolohydroximinoyl chloride 4 through the 1,3-dipolar cycloaddition reaction. The structures of the compounds were represented by1H NMR, MS, IR and elemental analysis.

[1,5]benzothiazepine; 1,3-dipolar cycloaddition; [1,2,4]oxadiazole; pyrazole

2012-10-19

刘方明(1966—)，男，教授，博士，主要从事杂环化学研究.E-mail：fmliu859@sohu.com

10.3969/j.issn.1674-232X.2013.01.006

O626.5

A

1674-232X(2013)01-0030-05