One-pot Synthesis of β-Carboline Derivatives Catalyzed by CuO Nanoparticles†

doi:10.7503/cjcu20180326

Abstract

Abstract:

Compounds containing β-carboline moiety have a variety of special biochemical and pharmacological activities. In order to explore the method for efficient synthesize β-carbolines, a novel method applied Pictet-Spengler cyclization and coupling oxidation in one-step was studied. Tryptophan esters and aromatic aldehydes were heated in N,N-Dimethylformamide via the promotion of nano CuO. Twenty-five compounds of 1,3-disubstituted-β-carbolines were obtained in moderate to excellent yield with subsequent isolation and purification. Attractive features of this method included simple operation, high efficiency and mild condition. Especially, nano CuO as catalyst and oxidant promoted cyclization and oxidation processes in creating β-carbolines motif.

Key words: Nano CuO, β-Carboline derivative;, Pictet-Spengler reaction, One-pot synthesis

CLC Number:

O626

TrendMD:

ZHANG Jin, SHI Tiancai, LUO Liwen, LIU Jia, LIU Rong, LIU Le, LIANG Ming, MA Yangmin. One-pot Synthesis of β-Carboline Derivatives Catalyzed by CuO Nanoparticles^†[J]. Chem. J. Chinese Universities, 2018, 39(11): 2411.

Figures/Tables 5

References 33

[1]	Domínguez G., Pérez-Castells J., Eur. J. Org. Chem, 2011, 2011(36), 7243—7253
[2]	Jiao W. H., Chen G. D., Gao H., Li J., Gu B. B., Xu T. T., Yu H. B., Shi G. H., Yang F., Yao X. S., Lin H. W., J. Nat. Prod., 2015, 78(1), 125—130
[3]	Ohishi K., Toume K., Arai M. A., Koyano T., Kowithayakorn T., Mizaguchi T., Itoh M., Ishibashi M., J. Nat. Prod., 2015, 78(5), 1139—1146
[4]	Furusato A., Kato H., Nehira T., Eguchi K., Kawabata T., Fujiwara Y., Lusong F., Mangindaan R. E. P., Voogd N. J. D., Takeya M., Org. Lett., 2014, 16(15), 3888—3891
[5]	Khokhar S., Feng Y. J., Carroll A. R., Campitelli M. R., Quinn R. J., Hooper J. N. A., Ekins M. G., Davis R. A., Tetrahedron, 2015, 71(36), 6204—6209
[6]	Vignoni M., Rasse-Suriani F. A. O., Butzbach K., Erra-Balsells R., Epe B., Cabrerizo F. M., Org. Biomol. Chem., 2013, 11(32), 5300—5309
[7]	Sakai R., Higa T., Jefford C. W., Bernardinelli G., J. Am. Chem. Soc., 1986, 108(20), 6404—6405
[8]	Ang K. H., Holmes M. J., Higa T., Hamann M. T., Kara U. A. K., Antimicrob. Agents. Ch., 2000, 44(6), 1645—1649
[9]	Bettarini F., Borgonovi G. E., Fiorani T., Gagliardi I., Caprioli V., Massardo P., Jij O., Hassanali A., Nyandat E., Chapya A., Insect Sci. Applic., 1993, 14(1), 93—99
[10]	Sun B., Morikawa T., Matsuda H., Tewtrakul S., Wu L. J., Harima S., Yoshikawa M., J. Nat. Prod., 2004, 67(9), 1464—1469
[11]	Duka T., Schutt B., Krause W., Dorow R., Mcdonald S., Fichte K., Brit. J. Clinical. Pharmaco., 2012, 35(4), 386—394
[12]	Ramesh S., Nagarajan R., J. Org. Chem., 2013, 78(2), 545—558
[13]	Mittal N., Sun D. X., Seidel D., Org. Lett., 2014, 16(3), 1012—1015
[14]	Zhu Y.P., Liu M. C., Cai Q., Jia F. C., Wu A. X., Chem. Eur. J., 2013, 19(31), 10132—10137
[15]	Condie G., Bergman G., Eur. J. Org. Chem, 2004, 2004(6), 1286—1297
[16]	Eagon S., Anderson M. O., Eur. J. Org. Chem., 2014, 2014(8), 1653—1665
[17]	Salehi P., Babanezhad-Harikandei K., Bararjanian M., Al-Harrasi A., Esmaeili M. A., Aliahmadi A., Med. Chem. Res., 2016, 25(9), 1895—1907
[18]	Dong J., Shi X. X., Yan J. J., Xing J., Zhang Q., Xiao S., Eur. J. Org. Chem., 2010, 2010(36), 6987—6992
[19]	Guo L., Fan W. X., Chen X. M., Ma Q., Chinese J. Org. Chem., 2013, 33(2), 332—338
	(郭亮, 范文玺, 陈雪梅, 马芹. 有机化学, 2013, 33(2), 332—338)
[20]	Hati S., Sen S., Tetrahedron Lett., 2016, 57(9), 1040—1043
[21]	Kamal A., Tangella Y., Manasa K. L., Sathish M., Srinivasulu V., Chetna J., Alarifi A., Org. Biomol. Chem., 2015, 13(32), 8652—8662
[22]	Ding S., Shi Z., Jiao N., Org. Lett., 2010, 12(7), 1540—1543
[23]	Tiruveedhula V. V. N. P. B., Methuku K., Deschamps J., Cook J. M., Org. Biomol. Chem., 2015, 13(43), 10705—10715
[24]	Yan Q., Gin E., Banwell M. G., Willis A. C., Carr P. D., Eur. J. Org. Chem., 2017, 82(8), 4328—4335
[25]	Wang T., Zhang D., Liao W., Chem. Commun., 2018, 54(16), 2048—2051
[26]	Joseph D. P., Stephen P. W., Org. Lett., 2010, 12(18), 4086—4089
[27]	Tang J. G., Liu H., Zhou Z. Y., Liu J. K., Syn. Comm., 2010, 40(10), 1411—1417
[28]	Zhang J., Liu J., Ma Y. M., Cheng P., Chinese J. Org. Chem., 2017, 37(3), 555—565
	(张金, 刘佳, 马养民, 程佩. 有机化学, 2017, 37(3), 555—565)
[29]	Liu L. L., Tai X. S., Yu G. L., Guo H. M., Meng Q. G., Chem. Res. Chinese Universities, 2016, 32(3), 443—450
[30]	Sang R., Cheng X., Li W. J., Luo P. F., Zhang Y., Nie R. F., Hai L., Wu Y., Chem. Res. Chinese Universities, 2017, 33(5), 811—815
[31]	Zhang J., Ren D. C., Ma Y. M., Wang W. F., Wu H., Tetrahedron., 2014, 70(34), 5274—5282
[32]	Zhang J., Liu J., Ma Y. M., Ren D. C., Cheng P., Zhao J., Zhang F., Yao Y., Bioorg. Med. Chem. Lett., 2016, 26(9), 2273—2277
[33]	Battini N., Padala A. K., Mupparapu N., Vishwakarma R. A., Ahmed Q. N., RSC Adv., 2014, 4(50), 26258—26263

Compd.	Appearance	Yield(%)	m. p./℃	HRMS, m/z[M+H]⁺(calcd.)
3a	White solid	87	243—244(242—245^[26])	348.0948(348.0979)
3b	Yellow solid	82	294—295(>260^[26])	348.0954(348.0979)
3c	Yellow solid	76	280—281	348.0962(348.0979)
3d	White solid	60	233—235(229—230^[26])	333.1248(333.1234)
3e	Yellow solid	78	235—237	304.1102(304.1081)
3f	Yellow solid	75	176—177(172—174^[27])	304.1095(304.1081)
3g	White solid	80	228—230	329.1276(329.1285)
3h	White solid	82	268—271	337.0735(337.0738)
Compd.	Appearance	Yield(%)	m. p./℃	HRMS, m/z[M+H]⁺(calcd.)
3i	White solid	83	262—265	381.0229(381.0233)
3j	White solid	62	229—230	345.1587(345.1598)
3k	White solid	57	231—218	331.1072(331.1077)
3l	Yellow solid	72	279—280	362.1128(362.1135)
3m	Yellow solid	79	275—278	376.1295(376.1292)
3n	Yellow solid	74	225—230	390.1441(390.1448)
3o	Yellow solid	76	225—226	404.1614(404.1605)
3p	Yellow solid	85	313—315	362.1129(362.1135)
3q	White solid	86	249—250	376.1286(376.1292)
3r	White solid	82	193—195	390.1443(390.1448)
3s	White solid	84	184—185	404.1601(404.1605)
3t	White solid	64	279—280	402.1448(402.1448)
3u	Yellow solid	77	272—273	362.1133(362.1135)
3v	Yellow solid	70	260—262	376.1288(376.1292)
3w	Yellow solid	63	220—221	390.1445(390.1448)
3x	Yellow solid	70	200—201	404.1601(404.1605)
3y	Yellow solid	60	261—262	402.1443(402.1448)

Compd.	Appearance	Yield(%)	m. p./℃	HRMS, m/z[M+H]⁺(calcd.)
3a	White solid	87	243—244(242—245^[26])	348.0948(348.0979)
3b	Yellow solid	82	294—295(>260^[26])	348.0954(348.0979)
3c	Yellow solid	76	280—281	348.0962(348.0979)
3d	White solid	60	233—235(229—230^[26])	333.1248(333.1234)
3e	Yellow solid	78	235—237	304.1102(304.1081)
3f	Yellow solid	75	176—177(172—174^[27])	304.1095(304.1081)
3g	White solid	80	228—230	329.1276(329.1285)
3h	White solid	82	268—271	337.0735(337.0738)
Compd.	Appearance	Yield(%)	m. p./℃	HRMS, m/z[M+H]⁺(calcd.)
3i	White solid	83	262—265	381.0229(381.0233)
3j	White solid	62	229—230	345.1587(345.1598)
3k	White solid	57	231—218	331.1072(331.1077)
3l	Yellow solid	72	279—280	362.1128(362.1135)
3m	Yellow solid	79	275—278	376.1295(376.1292)
3n	Yellow solid	74	225—230	390.1441(390.1448)
3o	Yellow solid	76	225—226	404.1614(404.1605)
3p	Yellow solid	85	313—315	362.1129(362.1135)
3q	White solid	86	249—250	376.1286(376.1292)
3r	White solid	82	193—195	390.1443(390.1448)
3s	White solid	84	184—185	404.1601(404.1605)
3t	White solid	64	279—280	402.1448(402.1448)
3u	Yellow solid	77	272—273	362.1133(362.1135)
3v	Yellow solid	70	260—262	376.1288(376.1292)
3w	Yellow solid	63	220—221	390.1445(390.1448)
3x	Yellow solid	70	200—201	404.1601(404.1605)
3y	Yellow solid	60	261—262	402.1443(402.1448)

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3a	12.14(s, 1H), 9.00(s, 1H), 8.77(s, 1H), 8.44(dd, J=19.4, 7.5 Hz, 3H), 7.94(t, J=7.9 Hz, 1H), 7.70(d, J=8.0 Hz, 1H), 7.64(t, J=7.4 Hz, 1H), 7.36(t, J=7.3 Hz, 1H), 3.95(s, 3H)	165.79, 148.11, 141.52, 139.47, 138.87, 136.77, 135.03, 134.68, 130.43, 129.75, 129.02, 123.58, 123.32, 122.21, 121.04, 120.63, 117.48, 112.65, 52.14
3b	12.13(s, 1H), 9.01(s, 1H), 8.47(d, J=8.2 Hz, 3H), 8.30(d, J=8.3 Hz, 2H), 7.67(d, J=20.4 Hz, 2H), 7.36(s, 1H), 3.95(s, 3H)	165.77, 143.62, 141.56, 139.40, 136.85, 134.80, 129.91, 129.07, 123.87, 122.21, 120.97, 120.68, 117.64, 112.70, 52.15
3c	12.02(s, 1H), 12.02(s, 1H), 9.00(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.24(dd, J=31.2, 15.7 Hz, 1H), 8.07—7.79(m, 3H), 7.73—7.50(m, 2H), 7.50—7.24(m, 1H), 3.90(s, 3H)	165.72, 148.60, 141.32, 139.83, 136.20, 135.29, 133.78, 132.04, 132.03, 130.34, 128.91, 128.64, 124.86, 122.29, 121.07, 120.54, 117.44, 112.50, 52.05
3d	8.99(s, 1H), 8.85(s, 1H), 8.23(d, J=7.9 Hz, 1H), 7.87(d, J=8.6 Hz, 2H), 7.61(t, J=11.8 Hz, 2H), 7.43—7.33(m, 1H), 7.01(d, J=8.6 Hz, 2H), 4.07(s, 3H), 3.85(s, 3H)	166.50, 159.83, 142.34, 140.11, 137.51, 134.54, 129.71, 129.12, 128.36, 121.68, 121.44, 120.55, 116.01, 114.09, 113.98, 111.46, 54.89, 52.18
3e	9.74(s, 1H), 8.95(d, J=10.5 Hz, 1H), 8.72(d, J=5.5 Hz, 2H), 8.26(d, J=7.9 Hz, 1H), 7.87(d, J=5.8 Hz, 2H), 7.74—7.58(m, 2H), 7.47—7.39(m, 1H), 4.08(s, 3H)	166.04, 149.85, 145.12, 140.54, 139.19, 137.86, 134.81, 130.21, 129.02, 122.65, 121.60, 121.36, 121.01, 117.55, 111.68, 52.37
3f	11.67(s, 1H), 8.96—8.91(m, 2H), 8.83(d, J=4.8 Hz, 1H), 8.25(d, J=7.8 Hz, 1H), 8.00—7.95(m, 1H), 7.71(d, J=8.2 Hz, 1H), 7.65(t, J=7.3 Hz, 1H), 7.44—7.38(m, 2H), 4.12(s, 3H)	166.24, 156.53, 147.72, 140.50, 137.07, 136.69, 136.15, 135.66, 130.18, 128.51, 123.10, 121.62, 121.40, 120.98, 120.33, 117.81, 111.83, 52.18
3g	8.88(s, 1H), 8.81(s, 1H), 8.22(d, J=7.9 Hz, 1H), 7.94(d, J=7.1 Hz, 2H), 7.61(d, J=8.0 Hz, 1H), 7.55(dd, J=14.7, 7.6 Hz, 4H), 7.47(t, J=7.3 Hz, 1H), 7.38(t, J=7.9 Hz, 2H), 4.05(s, 3H)	166.92, 142.98, 140.58, 138.31, 137.79, 136.48, 135.15, 129.83, 129.26, 129.23, 129.02, 128.72, 128.38, 122.17, 122.04, 121.18, 116.95, 111.90, 52.70
3h	12.06(s, 1H), 8.97(s, 1H), 8.46(d, J=7.9 Hz, 1H), 8.06—7.94(m, 2H), 7.68(dt, J=13.4, 8.0 Hz, 4H), 7.35(t, J=7.5 Hz, 1H), 3.95(s, 3H)	165.89, 141.50, 140.34, 139.48, 136.63, 134.54, 133.51, 130.68, 129.51, 128.87, 128.26, 127.28, 122.11, 121.05, 120.53, 117.15, 112.73, 52.10
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3i	11.99(s, 1H), 8.95(s, 1H), 8.44(d, J=7.9 Hz, 1H), 7.98(d, J=8.3 Hz, 2H), 7.84(d, J=8.3 Hz, 2H), 7.69(d, J=8.2 Hz, 1H), 7.62(t, J=7.5 Hz, 1H), 7.34(t, J=7.4 Hz, 1H), 3.94(s, 3H)	165.93, 141.46, 140.79, 136.66, 136.60, 134.50, 131.71, 130.67, 129.38, 128.81, 122.44, 122.09, 121.05, 120.50, 116.98, 112.69, 52.08
3j	8.96(s, 1H), 8.87(s, 1H), 8.24(d, J=7.9 Hz, 1H), 7.84(d, J=8.1 Hz, 2H), 7.71—7.49(m, 2H), 7.43—7.32(m, 3H), 4.07(s, 3H), 2.98(dt, J=13.8, 6.9 Hz, 1H), 1.30(s, 3H), 1.28(s, 3H)	166.50, 149.62, 142.66, 140.09, 137.59, 134.72, 134.62, 129.08, 128.38, 127.81, 126.72, 121.65, 121.47, 120.54, 116.21, 111.42, 52.16, 33.55, 23.42
3k	12.09(s, 1H), 12.09(s, 1H), 10.19(s, 1H), 10.19(s, 1H), 9.01(s, 1H), 9.01(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.27(d, J=8.2 Hz, 2H), 8.19(d, J=8.3 Hz, 2H), 7.72(d, J=8.2 Hz, 1H), 7.67—7.60(m, 1H), 7.41—7.33(m, 1H), 3.96(s, 3H)	193.01, 165.89, 142.95, 141.54, 140.52, 136.83, 136.14, 134.78, 129.89, 129.69, 129.34, 128.96, 122.15, 121.02, 120.61, 117.36, 112.75, 52.12
3l	12.13(s, 1H), 9.00(s, 1H), 8.48(d, J=8.5 Hz, 3H), 8.30(d, J=8.6 Hz, 2H), 7.79—7.58(m, 2H), 7.37(t, J=7.3 Hz, 1H), 4.43(d, J=7.1 Hz, 2H), 1.63—1.20(m, 3H)	165.24, 147.44, 143.67, 141.57, 139.43, 137.12, 134.78, 129.92, 129.87, 129.05, 123.88, 122.20, 120.98, 120.66, 117.57, 112.70, 60.77, 14.37
3m	11.97(s, 1H), 8.94(s, 1H), 8.46(d, J=7.9 Hz, 1H), 8.26(d, J=8.1 Hz, 1H), 8.01—7.80(m, 3H), 7.62(d, J=5.6 Hz, 2H), 7.36(ddd, J=7.9, 5.6, 2.3 Hz, 1H), 5.25—5.15(m, 1H), 1.37(d, J=6.2 Hz, 6H)	192.33, 164.69, 147.47, 143.72, 141.59, 139.46, 137.47, 134.76, 130.62, 129.92, 129.04, 124.26, 123.91, 122.19, 120.99, 120.65, 117.46, 112.72, 68.20, 21.80
3n	12.13(s, 1H), 8.99(s, 1H), 8.82(s, 1H), 8.49(d, J=7.8 Hz, 2H), 8.42(d, J=7.9 Hz, 1H), 7.95(t, J=8.0 Hz, 1H), 7.71(d, J=8.1 Hz, 1H), 7.65(t, J=7.5 Hz, 1H), 7.37(t, J=7.4 Hz, 1H), 4.39(t, J=6.6 Hz, 2H), 1.84—1.72(m, 2H), 1.56—1.44(m, 2H), 0.99(t, J=7.4 Hz, 3H)	148.18, 141.55, 139.41, 138.96, 137.08, 134.94, 134.66, 130.45, 129.82, 129.02, 123.56, 123.33, 122.21, 121.06, 120.62, 117.31, 112.67, 64.46, 30.42, 18.78, 13.66
3o	12.03(s, 1H), 8.96(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.26(dd, J=8.1, 0.9 Hz, 1H), 8.01—7.90(m, 2H), 7.86(s, 1H), 7.66—7.58(m, 2H), 7.36(s, 1H), 4.31(t, J=6.7 Hz, 2H), 1.80—1.69(m, 2H), 1.46—1.32(m, 4H), 0.91(t, J=7.1 Hz, 3H)	147.47, 143.69, 141.58, 139.44, 137.13, 134.80, 129.91, 129.08, 123.90, 122.24, 120.98, 120.67, 117.55, 112.72, 64.61, 28.03, 27.66, 21.83, 13.90
3p	12.15(s, 1H), 9.01(s, 1H), 8.79(s, 1H), 8.57—8.31(m, 3H), 7.95(s, 1H), 7.67(d, J=18.2 Hz, 2H), 7.38(d, J=7.2 Hz, 1H), 4.43(d, J=7.0 Hz, 2H), 1.40(t, J=6.9 Hz, 3H)	165.25, 148.15, 141.54, 139.51, 138.94, 137.09, 135.04, 134.68, 130.47, 129.75, 129.02, 123.58, 123.34, 122.21, 121.06, 120.63, 117.39, 112.66, 60.76, 14.37
3q	12.12(s, 1H), 8.97(s, 1H), 8.80(s, 1H), 8.46(dd, J=20.0, 8.1 Hz, 3H), 7.96(t, J=8.0 Hz, 1H), 7.74—7.61(m, 2H), 7.37(t, J=7. Hz, 1H), 5.26(s, 1H), 1.41(d, J=6.2 Hz, 6H)	164.68, 148.12, 141.53, 139.47, 138.95, 137.33, 135.02, 134.62, 130.45, 129.70, 128.99, 123.56, 123.34, 122.19, 121.05, 120.59, 117.30, 114.88, 112.65, 68.18, 21.80
3r	12.03(s, 1H), 8.97(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.26(d, J=7.4 Hz, 1H), 8.00—7.89(m, 2H), 7.86(t, J=7.6 Hz, 1H), 7.62(s, 2H), 7.39—7.30(m, 1H), 4.32(t, J=6.6 Hz, 2H), 1.78—1.64(m, 2H), 1.45(dd, J=15.0, 7.4 Hz, 2H), 0.95(t, J=7.4 Hz, 3H)	165.24, 155.49, 148.81, 141.34, 139.56, 136.49, 135.19, 133.61, 131.96, 131.89, 130.29, 128.90, 128.73, 124.84, 122.28, 121.06, 120.51, 117.29, 112.51, 64.38, 30.38, 18.69, 13.65
3s	12.15(s, 1H), 8.99(s, 1H), 8.82(s, 1H), 8.55—8.37(m, 3H), 7.96(t, J=8.0 Hz, 1H), 7.75—7.60(m, 2H), 7.37(t, J=7.5 Hz, 1H), 4.38(t, J=6.7 Hz, 2H), 1.80(s, 2H), 1.54—1.31(m, 4H), 0.92(t, J = 7.1 Hz, 3H)	165.28, 148.14, 141.53, 139.36, 138.93, 137.02, 134.93, 134.63, 130.43, 129.79, 129.02, 123.56, 123.33, 122.21, 121.04, 120.61, 117.33, 112.66, 64.74, 28.03, 27.71, 21.85, 13.88
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3t	12.11(s, 1H), 8.94(s, 1H), 8.47(d, J=8.6 Hz, 3H), 8.30(d, J=8.6 Hz, 2H), 7.70(d, J=8.2 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 5.40(s, 1H), 1.99(s, 2H), 1.83(s, 4H), 1.65(s, 2H)	164.89, 147.40, 143.69, 141.56, 137.38, 134.70, 129.85, 129.01, 123.86, 122.20, 120.97, 120.59, 117.44, 112.70, 77.30, 32.34, 23.47
3u	12.01(s, 1H), 8.98(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.28(dd, J=8.1, 0.8 Hz, 1H), 8.00—7.84(m, 3H), 7.62(d, J=5.4 Hz, 2H), 7.36(ddd, J=8.0, 5.8, 2.3 Hz, 1H), 4.37(q, J=7.1 Hz, 2H), 1.36(t, J=7.1 Hz, 3H)	165.21, 148.66, 141.32, 139.74, 136.48, 135.24, 133.74, 132.04, 132.01, 130.32, 128.89, 128.64, 124.85, 122.26, 121.07, 120.52, 117.34, 112.50, 60.68, 14.31
3v	12.00(s, 1H), 8.95(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.27(d, J=8.1 Hz, 1H), 7.91(ddd, J=24.5, 15.1, 7.4 Hz, 3H), 7.62(d, J=5.4 Hz, 2H), 7.42—7.29(m, 1H), 5.20(dt, J=12.4, 6.2 Hz, 1H), 1.36(d, J=6.2 Hz, 6H)	164.66, 148.74, 141.33, 139.62, 136.80, 135.17, 133.67, 132.02, 131.97, 130.30, 128.86, 128.63, 124.95, 124.84, 122.24, 121.07, 120.49, 117.23, 112.50, 68.07, 21.77
3w	12.13(s, 1H), 8.98(s, 1H), 8.48(d, J=8.7 Hz, 3H), 8.31(d, J=8.8 Hz, 2H), 7.71(d, J=8.2 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 4.38(t, J=6.7 Hz, 2H), 1.82—1.72(m, 2H), 1.54—1.42(m, 2H), 0.97(t, J=7.4 Hz, 3H)	165.25, 147.44, 143.67, 141.57, 139.40, 137.11, 134.77, 129.88, 129.05, 123.88, 122.21, 120.97, 120.65, 117.52, 112.71, 64.47, 30.42, 18.76, 13.67
3x	12.15(s, 1H), 9.00(s, 1H), 8.54-8.44(m, 3H), 8.36—8.29(m, 2H), 7.76—7.60(m, 2H), 7.42—7.33(m, 1H), 4.38(s, 2H), 1.84—1.74(m, 2H), 1.48—1.35(m, 4H), 0.92(t, J=7.1 Hz, 3H)	165.26, 147.45, 143.68, 141.57, 139.41, 137.12, 134.78, 129.99, 129.07, 123.89, 122.21, 120.97, 120.65, 117.54, 112.71, 64.76, 55.98, 28.03, 27.66, 21.84, 18.53
3y	12.12(s, 1H), 7.93(td, J=7.9, 3.2 Hz, 1H), 7.70(d, J=8.1 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 5.44—5.36(m, 1H), 2.07—1.95(m, 2H), 1.84(t, J=11.9 Hz, 4H), 1.72—1.59(m, 2H)	164.89, 148.11, 141.52, 139.31, 138.94, 137.28, 134.90, 134.55, 130.42, 129.75, 128.97, 123.52, 123.31, 122.20, 121.04, 120.55, 117.25, 115.44, 112.64, 77.29, 32.35, 23.44

Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3a	12.14(s, 1H), 9.00(s, 1H), 8.77(s, 1H), 8.44(dd, J=19.4, 7.5 Hz, 3H), 7.94(t, J=7.9 Hz, 1H), 7.70(d, J=8.0 Hz, 1H), 7.64(t, J=7.4 Hz, 1H), 7.36(t, J=7.3 Hz, 1H), 3.95(s, 3H)	165.79, 148.11, 141.52, 139.47, 138.87, 136.77, 135.03, 134.68, 130.43, 129.75, 129.02, 123.58, 123.32, 122.21, 121.04, 120.63, 117.48, 112.65, 52.14
3b	12.13(s, 1H), 9.01(s, 1H), 8.47(d, J=8.2 Hz, 3H), 8.30(d, J=8.3 Hz, 2H), 7.67(d, J=20.4 Hz, 2H), 7.36(s, 1H), 3.95(s, 3H)	165.77, 143.62, 141.56, 139.40, 136.85, 134.80, 129.91, 129.07, 123.87, 122.21, 120.97, 120.68, 117.64, 112.70, 52.15
3c	12.02(s, 1H), 12.02(s, 1H), 9.00(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.24(dd, J=31.2, 15.7 Hz, 1H), 8.07—7.79(m, 3H), 7.73—7.50(m, 2H), 7.50—7.24(m, 1H), 3.90(s, 3H)	165.72, 148.60, 141.32, 139.83, 136.20, 135.29, 133.78, 132.04, 132.03, 130.34, 128.91, 128.64, 124.86, 122.29, 121.07, 120.54, 117.44, 112.50, 52.05
3d	8.99(s, 1H), 8.85(s, 1H), 8.23(d, J=7.9 Hz, 1H), 7.87(d, J=8.6 Hz, 2H), 7.61(t, J=11.8 Hz, 2H), 7.43—7.33(m, 1H), 7.01(d, J=8.6 Hz, 2H), 4.07(s, 3H), 3.85(s, 3H)	166.50, 159.83, 142.34, 140.11, 137.51, 134.54, 129.71, 129.12, 128.36, 121.68, 121.44, 120.55, 116.01, 114.09, 113.98, 111.46, 54.89, 52.18
3e	9.74(s, 1H), 8.95(d, J=10.5 Hz, 1H), 8.72(d, J=5.5 Hz, 2H), 8.26(d, J=7.9 Hz, 1H), 7.87(d, J=5.8 Hz, 2H), 7.74—7.58(m, 2H), 7.47—7.39(m, 1H), 4.08(s, 3H)	166.04, 149.85, 145.12, 140.54, 139.19, 137.86, 134.81, 130.21, 129.02, 122.65, 121.60, 121.36, 121.01, 117.55, 111.68, 52.37
3f	11.67(s, 1H), 8.96—8.91(m, 2H), 8.83(d, J=4.8 Hz, 1H), 8.25(d, J=7.8 Hz, 1H), 8.00—7.95(m, 1H), 7.71(d, J=8.2 Hz, 1H), 7.65(t, J=7.3 Hz, 1H), 7.44—7.38(m, 2H), 4.12(s, 3H)	166.24, 156.53, 147.72, 140.50, 137.07, 136.69, 136.15, 135.66, 130.18, 128.51, 123.10, 121.62, 121.40, 120.98, 120.33, 117.81, 111.83, 52.18
3g	8.88(s, 1H), 8.81(s, 1H), 8.22(d, J=7.9 Hz, 1H), 7.94(d, J=7.1 Hz, 2H), 7.61(d, J=8.0 Hz, 1H), 7.55(dd, J=14.7, 7.6 Hz, 4H), 7.47(t, J=7.3 Hz, 1H), 7.38(t, J=7.9 Hz, 2H), 4.05(s, 3H)	166.92, 142.98, 140.58, 138.31, 137.79, 136.48, 135.15, 129.83, 129.26, 129.23, 129.02, 128.72, 128.38, 122.17, 122.04, 121.18, 116.95, 111.90, 52.70
3h	12.06(s, 1H), 8.97(s, 1H), 8.46(d, J=7.9 Hz, 1H), 8.06—7.94(m, 2H), 7.68(dt, J=13.4, 8.0 Hz, 4H), 7.35(t, J=7.5 Hz, 1H), 3.95(s, 3H)	165.89, 141.50, 140.34, 139.48, 136.63, 134.54, 133.51, 130.68, 129.51, 128.87, 128.26, 127.28, 122.11, 121.05, 120.53, 117.15, 112.73, 52.10
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3i	11.99(s, 1H), 8.95(s, 1H), 8.44(d, J=7.9 Hz, 1H), 7.98(d, J=8.3 Hz, 2H), 7.84(d, J=8.3 Hz, 2H), 7.69(d, J=8.2 Hz, 1H), 7.62(t, J=7.5 Hz, 1H), 7.34(t, J=7.4 Hz, 1H), 3.94(s, 3H)	165.93, 141.46, 140.79, 136.66, 136.60, 134.50, 131.71, 130.67, 129.38, 128.81, 122.44, 122.09, 121.05, 120.50, 116.98, 112.69, 52.08
3j	8.96(s, 1H), 8.87(s, 1H), 8.24(d, J=7.9 Hz, 1H), 7.84(d, J=8.1 Hz, 2H), 7.71—7.49(m, 2H), 7.43—7.32(m, 3H), 4.07(s, 3H), 2.98(dt, J=13.8, 6.9 Hz, 1H), 1.30(s, 3H), 1.28(s, 3H)	166.50, 149.62, 142.66, 140.09, 137.59, 134.72, 134.62, 129.08, 128.38, 127.81, 126.72, 121.65, 121.47, 120.54, 116.21, 111.42, 52.16, 33.55, 23.42
3k	12.09(s, 1H), 12.09(s, 1H), 10.19(s, 1H), 10.19(s, 1H), 9.01(s, 1H), 9.01(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.27(d, J=8.2 Hz, 2H), 8.19(d, J=8.3 Hz, 2H), 7.72(d, J=8.2 Hz, 1H), 7.67—7.60(m, 1H), 7.41—7.33(m, 1H), 3.96(s, 3H)	193.01, 165.89, 142.95, 141.54, 140.52, 136.83, 136.14, 134.78, 129.89, 129.69, 129.34, 128.96, 122.15, 121.02, 120.61, 117.36, 112.75, 52.12
3l	12.13(s, 1H), 9.00(s, 1H), 8.48(d, J=8.5 Hz, 3H), 8.30(d, J=8.6 Hz, 2H), 7.79—7.58(m, 2H), 7.37(t, J=7.3 Hz, 1H), 4.43(d, J=7.1 Hz, 2H), 1.63—1.20(m, 3H)	165.24, 147.44, 143.67, 141.57, 139.43, 137.12, 134.78, 129.92, 129.87, 129.05, 123.88, 122.20, 120.98, 120.66, 117.57, 112.70, 60.77, 14.37
3m	11.97(s, 1H), 8.94(s, 1H), 8.46(d, J=7.9 Hz, 1H), 8.26(d, J=8.1 Hz, 1H), 8.01—7.80(m, 3H), 7.62(d, J=5.6 Hz, 2H), 7.36(ddd, J=7.9, 5.6, 2.3 Hz, 1H), 5.25—5.15(m, 1H), 1.37(d, J=6.2 Hz, 6H)	192.33, 164.69, 147.47, 143.72, 141.59, 139.46, 137.47, 134.76, 130.62, 129.92, 129.04, 124.26, 123.91, 122.19, 120.99, 120.65, 117.46, 112.72, 68.20, 21.80
3n	12.13(s, 1H), 8.99(s, 1H), 8.82(s, 1H), 8.49(d, J=7.8 Hz, 2H), 8.42(d, J=7.9 Hz, 1H), 7.95(t, J=8.0 Hz, 1H), 7.71(d, J=8.1 Hz, 1H), 7.65(t, J=7.5 Hz, 1H), 7.37(t, J=7.4 Hz, 1H), 4.39(t, J=6.6 Hz, 2H), 1.84—1.72(m, 2H), 1.56—1.44(m, 2H), 0.99(t, J=7.4 Hz, 3H)	148.18, 141.55, 139.41, 138.96, 137.08, 134.94, 134.66, 130.45, 129.82, 129.02, 123.56, 123.33, 122.21, 121.06, 120.62, 117.31, 112.67, 64.46, 30.42, 18.78, 13.66
3o	12.03(s, 1H), 8.96(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.26(dd, J=8.1, 0.9 Hz, 1H), 8.01—7.90(m, 2H), 7.86(s, 1H), 7.66—7.58(m, 2H), 7.36(s, 1H), 4.31(t, J=6.7 Hz, 2H), 1.80—1.69(m, 2H), 1.46—1.32(m, 4H), 0.91(t, J=7.1 Hz, 3H)	147.47, 143.69, 141.58, 139.44, 137.13, 134.80, 129.91, 129.08, 123.90, 122.24, 120.98, 120.67, 117.55, 112.72, 64.61, 28.03, 27.66, 21.83, 13.90
3p	12.15(s, 1H), 9.01(s, 1H), 8.79(s, 1H), 8.57—8.31(m, 3H), 7.95(s, 1H), 7.67(d, J=18.2 Hz, 2H), 7.38(d, J=7.2 Hz, 1H), 4.43(d, J=7.0 Hz, 2H), 1.40(t, J=6.9 Hz, 3H)	165.25, 148.15, 141.54, 139.51, 138.94, 137.09, 135.04, 134.68, 130.47, 129.75, 129.02, 123.58, 123.34, 122.21, 121.06, 120.63, 117.39, 112.66, 60.76, 14.37
3q	12.12(s, 1H), 8.97(s, 1H), 8.80(s, 1H), 8.46(dd, J=20.0, 8.1 Hz, 3H), 7.96(t, J=8.0 Hz, 1H), 7.74—7.61(m, 2H), 7.37(t, J=7. Hz, 1H), 5.26(s, 1H), 1.41(d, J=6.2 Hz, 6H)	164.68, 148.12, 141.53, 139.47, 138.95, 137.33, 135.02, 134.62, 130.45, 129.70, 128.99, 123.56, 123.34, 122.19, 121.05, 120.59, 117.30, 114.88, 112.65, 68.18, 21.80
3r	12.03(s, 1H), 8.97(s, 1H), 8.48(d, J=7.9 Hz, 1H), 8.26(d, J=7.4 Hz, 1H), 8.00—7.89(m, 2H), 7.86(t, J=7.6 Hz, 1H), 7.62(s, 2H), 7.39—7.30(m, 1H), 4.32(t, J=6.6 Hz, 2H), 1.78—1.64(m, 2H), 1.45(dd, J=15.0, 7.4 Hz, 2H), 0.95(t, J=7.4 Hz, 3H)	165.24, 155.49, 148.81, 141.34, 139.56, 136.49, 135.19, 133.61, 131.96, 131.89, 130.29, 128.90, 128.73, 124.84, 122.28, 121.06, 120.51, 117.29, 112.51, 64.38, 30.38, 18.69, 13.65
3s	12.15(s, 1H), 8.99(s, 1H), 8.82(s, 1H), 8.55—8.37(m, 3H), 7.96(t, J=8.0 Hz, 1H), 7.75—7.60(m, 2H), 7.37(t, J=7.5 Hz, 1H), 4.38(t, J=6.7 Hz, 2H), 1.80(s, 2H), 1.54—1.31(m, 4H), 0.92(t, J = 7.1 Hz, 3H)	165.28, 148.14, 141.53, 139.36, 138.93, 137.02, 134.93, 134.63, 130.43, 129.79, 129.02, 123.56, 123.33, 122.21, 121.04, 120.61, 117.33, 112.66, 64.74, 28.03, 27.71, 21.85, 13.88
Compd.	¹H NMR(400 MHz), δ	¹³C NMR(100 MHz), δ
3t	12.11(s, 1H), 8.94(s, 1H), 8.47(d, J=8.6 Hz, 3H), 8.30(d, J=8.6 Hz, 2H), 7.70(d, J=8.2 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 5.40(s, 1H), 1.99(s, 2H), 1.83(s, 4H), 1.65(s, 2H)	164.89, 147.40, 143.69, 141.56, 137.38, 134.70, 129.85, 129.01, 123.86, 122.20, 120.97, 120.59, 117.44, 112.70, 77.30, 32.34, 23.47
3u	12.01(s, 1H), 8.98(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.28(dd, J=8.1, 0.8 Hz, 1H), 8.00—7.84(m, 3H), 7.62(d, J=5.4 Hz, 2H), 7.36(ddd, J=8.0, 5.8, 2.3 Hz, 1H), 4.37(q, J=7.1 Hz, 2H), 1.36(t, J=7.1 Hz, 3H)	165.21, 148.66, 141.32, 139.74, 136.48, 135.24, 133.74, 132.04, 132.01, 130.32, 128.89, 128.64, 124.85, 122.26, 121.07, 120.52, 117.34, 112.50, 60.68, 14.31
3v	12.00(s, 1H), 8.95(s, 1H), 8.47(d, J=7.9 Hz, 1H), 8.27(d, J=8.1 Hz, 1H), 7.91(ddd, J=24.5, 15.1, 7.4 Hz, 3H), 7.62(d, J=5.4 Hz, 2H), 7.42—7.29(m, 1H), 5.20(dt, J=12.4, 6.2 Hz, 1H), 1.36(d, J=6.2 Hz, 6H)	164.66, 148.74, 141.33, 139.62, 136.80, 135.17, 133.67, 132.02, 131.97, 130.30, 128.86, 128.63, 124.95, 124.84, 122.24, 121.07, 120.49, 117.23, 112.50, 68.07, 21.77
3w	12.13(s, 1H), 8.98(s, 1H), 8.48(d, J=8.7 Hz, 3H), 8.31(d, J=8.8 Hz, 2H), 7.71(d, J=8.2 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 4.38(t, J=6.7 Hz, 2H), 1.82—1.72(m, 2H), 1.54—1.42(m, 2H), 0.97(t, J=7.4 Hz, 3H)	165.25, 147.44, 143.67, 141.57, 139.40, 137.11, 134.77, 129.88, 129.05, 123.88, 122.21, 120.97, 120.65, 117.52, 112.71, 64.47, 30.42, 18.76, 13.67
3x	12.15(s, 1H), 9.00(s, 1H), 8.54-8.44(m, 3H), 8.36—8.29(m, 2H), 7.76—7.60(m, 2H), 7.42—7.33(m, 1H), 4.38(s, 2H), 1.84—1.74(m, 2H), 1.48—1.35(m, 4H), 0.92(t, J=7.1 Hz, 3H)	165.26, 147.45, 143.68, 141.57, 139.41, 137.12, 134.78, 129.99, 129.07, 123.89, 122.21, 120.97, 120.65, 117.54, 112.71, 64.76, 55.98, 28.03, 27.66, 21.84, 18.53
3y	12.12(s, 1H), 7.93(td, J=7.9, 3.2 Hz, 1H), 7.70(d, J=8.1 Hz, 1H), 7.64(t, J=7.6 Hz, 1H), 7.36(t, J=7.4 Hz, 1H), 5.44—5.36(m, 1H), 2.07—1.95(m, 2H), 1.84(t, J=11.9 Hz, 4H), 1.72—1.59(m, 2H)	164.89, 148.11, 141.52, 139.31, 138.94, 137.28, 134.90, 134.55, 130.42, 129.75, 128.97, 123.52, 123.31, 122.20, 121.04, 120.55, 117.25, 115.44, 112.64, 77.29, 32.35, 23.44