Synthesis and Anti-tumor Activity of Novel Amino Acid Glyceroglycolipid†

doi:10.7503/cjcu2015405

Abstract

Abstract:

Glyceroglycolipids have been identified as one of the most important anticancer drug. In this work, novel amino acid glyceroglycolipids were synthesized through the esterification of glycosylglycerol and N-acyl amino acid and characterized by means of ¹H NMR and ESI-MS. The anti-tumor activities against human breast cancer cell line, human liver cancer cell line and chronic myeloid leukemia cell line in vitro were tested by MTT method. The preliminary results demonstrated that compounds 27(IC₅₀=3.53, 4.71, 4.13 μmol/L), 28(IC₅₀=4.35, 4.57, 5.79 μmol/L), 31(IC₅₀=3.91, 3.73, 4.54 μmol/L) and 32(IC₅₀=5.17, 5.52, 5.93 μmol/L) exhibited significant anti-tumor activities. The preliminary studies on the structure-activity relationship showed that when the acyl was decanoyl or lauroyl, good activity was exhibited in all the eight different kinds of glycosyl diacylglycerols. The preliminary prediction of this type of compound had certain inhibitory effect on the growth of tumor cells, they are non-toxic to normal cells. Such novel amino acid glyceroglycolipids as antineoplastic drugs or excellent surfactants could be widely investigated in the future.

Key words: Glyceroglycolipid, Glucose, Amino acid, Antineoplastic

CLC Number:

O629

TrendMD:

AN Dong, YE Zhiwen, ZHOU Mi. Synthesis and Anti-tumor Activity of Novel Amino Acid Glyceroglycolipid^†[J]. Chem. J. Chinese Universities, 2015, 36(12): 2427.

Figures/Tables 9

Scheme 1 Synthetic routes of title compounds 27—34 7, 19, 27: R1=H, R2=C9H19; 8, 20, 28: R1=H, R2=C11H23; 9, 21, 29: R1=H, R2=C13H27; 10, 22, 30: R1=H, R2=C15H31; 11, 23, 31: R1=CH(CH3)2, R2=C9H19; 12, 24, 32: R1=CH(CH3)2, R2=C11H23; 13, 25, 33: R1=CH(CH3)2, R2=C13H27; 14, 26, 34: R1=CH(CH3)2, R2=C15H31

Table 1 Melting points for compounds 7—14

Compd.	m. p.(ref.)/℃	Compd.	m. p.(ref.)/℃
7	112.3—113.7(112.3—113.8^[17])	11	105.5—106.7(105.8—106.9^[18])
8	118.3—119.1(117.5—119.3^[18])	12	103.3—105.1(103.8—105.3^[17])
9	120.2—121.7(119.1—120.6^[19])	13	85.1—86.9(86.4—87.7^[17])
10	121.3—122.6(120.4—121.7^[19])	14	82.1—83.3(83.1—84.4^[19])

Table 2 Appearance, yields, melting points and optical rotation of compounds 19—34

Compd.	Appearance	Yield(%)	m. p./℃	[α $] D 20$ /(°)(c=1.0, CHCl₃)
19	White solid	81.2	93.5—95.3	+4.2
20	White solid	82.3	71.5—73.1	+3.9
21	Pale oil	73.9	—	+4.4
22	Pale oil	52.6	—	+5.1
23	Yellow liquid	77.3	—	+7.3
24	Pale liquid	68.1	—	+6.9
25	Oily liquid	61.3	—	+8.1
26	Oily liquid	47.7	—	+6.3
27	White solid	92.4	107.5—109.1	-33.7
28	White solid	93.1	82.7—83.5	-33.9
29	Yellow liquid	83.1	—	-52.7
30	Yellow liquid	71.9	—	-34.3
31	White solid	82.9	63.2—64.7	-43.3
32	White liquid	71.9	—	-24.9
33	White liquid	74.3	—	-32.7
34	Yellow liquid	51.7	—	-24.3

Table 2 Appearance, yields, melting points and optical rotation of compounds 19—34

Compd.	Appearance	Yield(%)	m. p./℃	[α $] D 20$ /(°)(c=1.0, CHCl₃)
19	White solid	81.2	93.5—95.3	+4.2
20	White solid	82.3	71.5—73.1	+3.9
21	Pale oil	73.9	—	+4.4
22	Pale oil	52.6	—	+5.1
23	Yellow liquid	77.3	—	+7.3
24	Pale liquid	68.1	—	+6.9
25	Oily liquid	61.3	—	+8.1
26	Oily liquid	47.7	—	+6.3
27	White solid	92.4	107.5—109.1	-33.7
28	White solid	93.1	82.7—83.5	-33.9
29	Yellow liquid	83.1	—	-52.7
30	Yellow liquid	71.9	—	-34.3
31	White solid	82.9	63.2—64.7	-43.3
32	White liquid	71.9	—	-24.9
33	White liquid	74.3	—	-32.7
34	Yellow liquid	51.7	—	-24.3

Table 3 ESI-MS and elemental analysis data of compounds 19—34

Compd.	ESI-MS, m/z, [M+Na]⁺	Elemental analysis(%, calcd.)
Compd.	ESI-MS, m/z, [M+Na]⁺	C	H	N
19	1059.73	71.02(70.63)	7.88(8.16)	2.79(2.70)
20	1115.72	71.85(71.40)	8.67(8.48)	2.37(2.56)
21	1171.79	72.47(72.09)	8.93(8.77)	2.29(2.44)
22	1227.92	72.87(72.72)	9.31(9.03)	2.11(2.32)
23	1143.76	71.93(71.75)	8.31(8.63)	2.37(2.50)
24	1199.89	72.66(72.42)	8.72(8.90)	2.41(2.38)
25	1255.61	73.25(73.02)	9.02(9.15)	2.47(2.27)
26	1311.73	73.73(73.57)	9.19(9.38)	2.35(2.17)
27	699.47	58.69(58.56)	9.11(8.94)	4.03(4.14)
28	755.51	60.89(60.63)	9.51(9.35)	3.63(3.82)
29	811.47	62.66(62.41)	9.53(9.71)	3.41(3.55)
30	867.66	63.67(63.95)	9.83(10.02)	3.52(3.31)
31	783.57	61.83(61.55)	9.61(9.54)	3.39(3.68)
32	839.63	63.47(63.21)	9.95(9.87)	3.23(3.43)
33	895.67	64.79(64.65)	10.39(10.16)	3.02(3.21)
34	951.78	66.27(65.91)	10.13(10.41)	3.27(3.01)

Table 4 1H NMR data of compounds 19—26

Compd.	¹H NMR(500 MHz, CDCl₃), δ
19	7.33—7.27(m, 18H, ArH), 7.15—7.14(m, 2H, ArH), 6.08—6.01(m, 2H, 2NH), 5.60—5.58(m, 1H, 1'-H), 4.93—4.91(m, 1H, 2-H), 4.86—4.84(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.73—4.72(m, 1H, 3'b-PhCH), 4.58—4.56(m, 1H, 6'a-PhCH), 4.32—4.31(m, 1H, 6'b-PhCH), 4.31—4.27(m, 2H, 1-H), 4.27—4.26(m, 1H, 3a-H), 3.97—3.95(m, 1H, 6'a-CH), 3.88—3.87(m, 1H, 3b-H), 3.74—3.72(m, 1H, 5'-H), 3.64—3.63(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.58—3.56(m, 1H, 4'-H), 3.52—3.50(m, 2H, 6'-H), 2.23—2.16(m, 4H, 2CH₂), 1.66—1.64(m, 2H, CH₂), 1.63—1.61(m, 4H, 2CH₂), 1.29—1.26[m, 24H, 2(CH₂)₆], 0.88—0.86(m, 6H, 2CH₃)
20	7.34—7.28(m, 18H, ArH), 7.16—7.14(m, 2H, ArH), 6.10—6.06(m, 2H, 2NH), 5.66—5.61(m, 1H, 1'-H), 4.95—4.92(m, 1H, 2-H), 4.88—4.86(m, 2H, 4'-PhCH₂), 4.81—4.80(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.80—4.78(m, 1H, 3'b-PhCH), 4.63—4.61(m, 1H, 6'a-PhCH), 4.40—4.37(m, 1H, 6'b-PhCH), 4.34—4.30(m, 2H, 1-H), 4.29—4.26(m, 1H, 3a-H), 4.02—3.97(m, 1H, 6'a-PhCH), 3.95—3.93(m, 1H, 3b-H), 3.77—3.75(m, 1H, 5'-H), 3.67—3.65(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.59—3.57(m, 1H, 4'-H), 3.56—3.52(m, 2H, 6'-H), 2.27—2.20(m, 4H, 2CH₂), 1.70—1.66(m, 2H, CH₂), 1.65—1.63(m, 4H, 2CH₂), 1.31—1.28[m, 32H, 2(CH₂)₈], 0.90—0.87(m, 6H, 2CH₃)
21	7.31—7.27(m, 18H, ArH), 7.14—7.12(m, 2H, ArH), 6.10—6.09(m, 2H, 2NH), 5.61—5.59(m, 1H, 1'-H), 4.93—4.91(m, 1H, 2-H), 4.86—4.84(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.73—4.72(m, 1H, 3'b-PhCH), 4.58—4.56(m, 1H, 6'a-PhCH), 4.32—4.31(m, 1H, 6'b-PhCH), 4.31—4.27(m, 2H, 1-H), 4.27—4. 26(m, 1H, 3a-H), 3.97—3.95(m, 1H, 6'a-PhCH), 3.88—3.87(m, 1H, 3b-H), 3.74—3.72(m, 1H, 5'-H), 3.64—3.63(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.58—3.56(m, 1H, 4'-H), 3.52—3.50(m, 2H, 6'-H), 2.23—2.16(m, 4H, 2CH₂), 1.66—1.64(m, 2H, CH₂), 1.63—1.61(m, 4H, 2CH₂), 1.29—1.26[m, 40H, 2(CH₂)₁₀], 0.88—0.86(m, 6H, 2CH₃)
22	7.32—7.28(m, 18H, ArH), 7.17—7.15(m, 2H, ArH), 6.08—6.01(m, 2H, 2NH), 5.60—5.58(m, 1H, 1'-H), 4.95—4.93(m, 1H, 2-H), 4.87—4.85(m, 2H, 4'-PhCH₂), 4.84—4.82(m, 1H, 3'a-PhCH), 4.78—4.76(m, 2H, 2'-PhCH₂), 4.75—4.73(m, 1H, 3'b-PhCH), 4.60—4.58(m, 1H, 6'a-PhCH), 4.35—4.32(m, 1H, 6'b-PhCH), 4.31—4.28(m, 2H, 1-H), 4.27—4.25(m, 1H, 3a-H), 3.98—3.96(m, 1H, 6'a-PhCH), 3.90—3.89(m, 1H, 3b-H), 3.77—3.74(m, 1H, 5'-H), 3.66—3.64(m, 1H, 3'-H), 3.63—3.61(m, 1H, 2'-H), 3.60—3.58(m, 1H, 4'-H), 3.57—3.54
22	(m, 2H, 6'-H), 2.22—2.19(m, 4H, 2CH₂), 1.68—1.65(m, 2H, CH₂), 1.64—1.61(m, 4H, 2CH₂), 1.30—1.27[m, 48H, 2(CH₂)₁₂], 0.89—0.85(m, 6H, 2CH₃)
23	7.35—7.26(m, 18H, ArH), 7.27—7.22(m, 2H, ArH), 6.08—6.00(m, 2H, 2NH), 5.61—5.60(m, 1H, 1'-H), 5.40—5.39(m, 1H, 2-H), 5.31—5.24(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 2H, 3'-PhCH), 4.81—4.80(m, 2H, 2'-PhCH₂), 4.64—4.61(m, 2H, 6'-PhCH₂), 4.60—4.59(m, 2H, 1-H), 4.56—4.55(m, 2H, 2COCHNH), 4.49—4.47(m, 1H, 3-H), 3.72—3.70(m, 1H, 5'-H), 3.56—3.54(m, 1H, 3'-H), 3.50—3.48(m, 1H, 2'-H), 3.47—3.45(m, 2H, 6'-H), 3.44—3.42(m, 1H, 4'-H), 2.31—2.27[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.67—1.65(m, 4H, 2CH₂), 1.29—1.27[m, 24H, 2(CH₂)₆], 0.90—0.87(m, 18H, 6CH₃)
24	7.36—7.27(m, 18H, ArH), 7.25—7.23(m, 2H, ArH), 6.12—6.07(m, 2H, 2NH), 5.65—5.62(m, 1H, 1'-H), 5.44—5.41(m, 1H, 2-H), 5.35—5.27(m, 2H, 4'-PhCH₂), 4.87—4.85(m, 2H, 3'-PhCH), 4.83—4.81(m, 2H, 2'-PhCH₂), 4.65—4.62(m, 2H, 6'-PhCH₂), 4.61—4.58(m, 2H, 1-H), 4.57—4.55(m, 2H, 2COCHNH), 4.51—4.49(m, 1H, 3-H), 3.75—3.73(m, 1H, 5'-H), 3.60—3.58(m, 1H, 3'-H), 3.53—3.50(m, 1H, 2'-H), 3.49—3.47(m, 2H, 6'-H), 3.45—3.43(m, 1H, 4'-H), 2.32—2.28[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.68—1.66(m, 4H, 2CH₂), 1.30—1.28[m, 32H, 2(CH₂)₈], 0.93—0.88(m, 18H, 6CH₃)
25	7.36—7.26(m, 18H, ArH), 7.28—7.24(m, 2H, ArH), 6.08—6.00(m, 2H, 2NH), 5.61—5.60(m, 1H, 1'-H), 5.40—5.39(m, 1H, 2-H), 5.31—5.24(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 2H, 3'-PhCH), 4.81—4.80(m, 2H, 2'-PhCH₂), 4.64—4.61(m, 2H, 6'-PhCH₂), 4.60—4.59(m, 2H, 1-H), 4.56—4.55(m, 2H, 2COCHNH), 4.49—4.47(m, 1H, 3-H), 3.72—3.70(m, 1H, 5'-H), 3.56—3.54(m, 1H, 3'-H), 3.50—3.48(m, 1H, 2'-H), 3.47—3.45(m, 2H, 6'-H), 3.53(m, 1H, 4'-H), 2.31—2.27[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.67—1.65(m, 4H, 2CH₂), 1.29—1.27[m, 40H, 2(CH₂)₁₀], 0.90—0.87(m, 18H, 6CH₃)
26	7.37—7.28(m, 18H, ArH), 7.28—7.20(m, 2H, ArH), 6.09—6.02(m, 2H, 2NH), 5.63—5.61(m, 1H, 1'-H), 5.54—5.51(m, 1H, 2-H), 5.38—5.34(m, 2H, 4'-PhCH₂), 4.89—4.85(m, 2H, 3'-PhCH), 4.83—4.80(m, 2H, 2'-PhCH₂), 4.70—4.67(m, 2H, 6'-PhCH₂), 4.65—4.62(m, 2H, 1-H), 4.58—4.56(m, 2H, 2COCHNH), 4.53—4.51(m, 1H, 3-H), 3.73—3.71(m, 1H, 5'-H), 3.60—3.56(m, 1H, 3'-H), 3.52—3.49(m, 1H, 2'-H), 3.48—3.46(m, 2H, 6'-H), 3.43—3.41(m, 1H, 4'-H), 2.32—2.28[m, 2H, 2CH(CH₃)₂], 2.27—2.23(m, 4H, 2NHCOCH₂), 1.69—1.65(m, 4H, 2CH₂), 1.31—1.28[m, 24H, 2(CH₂)₁₂], 0.92—0.88(m, 18H, 6CH₃)

Table 4 1H NMR data of compounds 19—26

Compd.	¹H NMR(500 MHz, CDCl₃), δ
19	7.33—7.27(m, 18H, ArH), 7.15—7.14(m, 2H, ArH), 6.08—6.01(m, 2H, 2NH), 5.60—5.58(m, 1H, 1'-H), 4.93—4.91(m, 1H, 2-H), 4.86—4.84(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.73—4.72(m, 1H, 3'b-PhCH), 4.58—4.56(m, 1H, 6'a-PhCH), 4.32—4.31(m, 1H, 6'b-PhCH), 4.31—4.27(m, 2H, 1-H), 4.27—4.26(m, 1H, 3a-H), 3.97—3.95(m, 1H, 6'a-CH), 3.88—3.87(m, 1H, 3b-H), 3.74—3.72(m, 1H, 5'-H), 3.64—3.63(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.58—3.56(m, 1H, 4'-H), 3.52—3.50(m, 2H, 6'-H), 2.23—2.16(m, 4H, 2CH₂), 1.66—1.64(m, 2H, CH₂), 1.63—1.61(m, 4H, 2CH₂), 1.29—1.26[m, 24H, 2(CH₂)₆], 0.88—0.86(m, 6H, 2CH₃)
20	7.34—7.28(m, 18H, ArH), 7.16—7.14(m, 2H, ArH), 6.10—6.06(m, 2H, 2NH), 5.66—5.61(m, 1H, 1'-H), 4.95—4.92(m, 1H, 2-H), 4.88—4.86(m, 2H, 4'-PhCH₂), 4.81—4.80(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.80—4.78(m, 1H, 3'b-PhCH), 4.63—4.61(m, 1H, 6'a-PhCH), 4.40—4.37(m, 1H, 6'b-PhCH), 4.34—4.30(m, 2H, 1-H), 4.29—4.26(m, 1H, 3a-H), 4.02—3.97(m, 1H, 6'a-PhCH), 3.95—3.93(m, 1H, 3b-H), 3.77—3.75(m, 1H, 5'-H), 3.67—3.65(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.59—3.57(m, 1H, 4'-H), 3.56—3.52(m, 2H, 6'-H), 2.27—2.20(m, 4H, 2CH₂), 1.70—1.66(m, 2H, CH₂), 1.65—1.63(m, 4H, 2CH₂), 1.31—1.28[m, 32H, 2(CH₂)₈], 0.90—0.87(m, 6H, 2CH₃)
21	7.31—7.27(m, 18H, ArH), 7.14—7.12(m, 2H, ArH), 6.10—6.09(m, 2H, 2NH), 5.61—5.59(m, 1H, 1'-H), 4.93—4.91(m, 1H, 2-H), 4.86—4.84(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 1H, 3'a-PhCH), 4.77—4.75(m, 2H, 2'-PhCH₂), 4.73—4.72(m, 1H, 3'b-PhCH), 4.58—4.56(m, 1H, 6'a-PhCH), 4.32—4.31(m, 1H, 6'b-PhCH), 4.31—4.27(m, 2H, 1-H), 4.27—4. 26(m, 1H, 3a-H), 3.97—3.95(m, 1H, 6'a-PhCH), 3.88—3.87(m, 1H, 3b-H), 3.74—3.72(m, 1H, 5'-H), 3.64—3.63(m, 1H, 3'-H), 3.63—3.59(m, 1H, 2'-H), 3.58—3.56(m, 1H, 4'-H), 3.52—3.50(m, 2H, 6'-H), 2.23—2.16(m, 4H, 2CH₂), 1.66—1.64(m, 2H, CH₂), 1.63—1.61(m, 4H, 2CH₂), 1.29—1.26[m, 40H, 2(CH₂)₁₀], 0.88—0.86(m, 6H, 2CH₃)
22	7.32—7.28(m, 18H, ArH), 7.17—7.15(m, 2H, ArH), 6.08—6.01(m, 2H, 2NH), 5.60—5.58(m, 1H, 1'-H), 4.95—4.93(m, 1H, 2-H), 4.87—4.85(m, 2H, 4'-PhCH₂), 4.84—4.82(m, 1H, 3'a-PhCH), 4.78—4.76(m, 2H, 2'-PhCH₂), 4.75—4.73(m, 1H, 3'b-PhCH), 4.60—4.58(m, 1H, 6'a-PhCH), 4.35—4.32(m, 1H, 6'b-PhCH), 4.31—4.28(m, 2H, 1-H), 4.27—4.25(m, 1H, 3a-H), 3.98—3.96(m, 1H, 6'a-PhCH), 3.90—3.89(m, 1H, 3b-H), 3.77—3.74(m, 1H, 5'-H), 3.66—3.64(m, 1H, 3'-H), 3.63—3.61(m, 1H, 2'-H), 3.60—3.58(m, 1H, 4'-H), 3.57—3.54
22	(m, 2H, 6'-H), 2.22—2.19(m, 4H, 2CH₂), 1.68—1.65(m, 2H, CH₂), 1.64—1.61(m, 4H, 2CH₂), 1.30—1.27[m, 48H, 2(CH₂)₁₂], 0.89—0.85(m, 6H, 2CH₃)
23	7.35—7.26(m, 18H, ArH), 7.27—7.22(m, 2H, ArH), 6.08—6.00(m, 2H, 2NH), 5.61—5.60(m, 1H, 1'-H), 5.40—5.39(m, 1H, 2-H), 5.31—5.24(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 2H, 3'-PhCH), 4.81—4.80(m, 2H, 2'-PhCH₂), 4.64—4.61(m, 2H, 6'-PhCH₂), 4.60—4.59(m, 2H, 1-H), 4.56—4.55(m, 2H, 2COCHNH), 4.49—4.47(m, 1H, 3-H), 3.72—3.70(m, 1H, 5'-H), 3.56—3.54(m, 1H, 3'-H), 3.50—3.48(m, 1H, 2'-H), 3.47—3.45(m, 2H, 6'-H), 3.44—3.42(m, 1H, 4'-H), 2.31—2.27[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.67—1.65(m, 4H, 2CH₂), 1.29—1.27[m, 24H, 2(CH₂)₆], 0.90—0.87(m, 18H, 6CH₃)
24	7.36—7.27(m, 18H, ArH), 7.25—7.23(m, 2H, ArH), 6.12—6.07(m, 2H, 2NH), 5.65—5.62(m, 1H, 1'-H), 5.44—5.41(m, 1H, 2-H), 5.35—5.27(m, 2H, 4'-PhCH₂), 4.87—4.85(m, 2H, 3'-PhCH), 4.83—4.81(m, 2H, 2'-PhCH₂), 4.65—4.62(m, 2H, 6'-PhCH₂), 4.61—4.58(m, 2H, 1-H), 4.57—4.55(m, 2H, 2COCHNH), 4.51—4.49(m, 1H, 3-H), 3.75—3.73(m, 1H, 5'-H), 3.60—3.58(m, 1H, 3'-H), 3.53—3.50(m, 1H, 2'-H), 3.49—3.47(m, 2H, 6'-H), 3.45—3.43(m, 1H, 4'-H), 2.32—2.28[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.68—1.66(m, 4H, 2CH₂), 1.30—1.28[m, 32H, 2(CH₂)₈], 0.93—0.88(m, 18H, 6CH₃)
25	7.36—7.26(m, 18H, ArH), 7.28—7.24(m, 2H, ArH), 6.08—6.00(m, 2H, 2NH), 5.61—5.60(m, 1H, 1'-H), 5.40—5.39(m, 1H, 2-H), 5.31—5.24(m, 2H, 4'-PhCH₂), 4.83—4.82(m, 2H, 3'-PhCH), 4.81—4.80(m, 2H, 2'-PhCH₂), 4.64—4.61(m, 2H, 6'-PhCH₂), 4.60—4.59(m, 2H, 1-H), 4.56—4.55(m, 2H, 2COCHNH), 4.49—4.47(m, 1H, 3-H), 3.72—3.70(m, 1H, 5'-H), 3.56—3.54(m, 1H, 3'-H), 3.50—3.48(m, 1H, 2'-H), 3.47—3.45(m, 2H, 6'-H), 3.53(m, 1H, 4'-H), 2.31—2.27[m, 2H, 2CH(CH₃)₂], 2.25—2.20(m, 4H, 2NHCOCH₂), 1.67—1.65(m, 4H, 2CH₂), 1.29—1.27[m, 40H, 2(CH₂)₁₀], 0.90—0.87(m, 18H, 6CH₃)
26	7.37—7.28(m, 18H, ArH), 7.28—7.20(m, 2H, ArH), 6.09—6.02(m, 2H, 2NH), 5.63—5.61(m, 1H, 1'-H), 5.54—5.51(m, 1H, 2-H), 5.38—5.34(m, 2H, 4'-PhCH₂), 4.89—4.85(m, 2H, 3'-PhCH), 4.83—4.80(m, 2H, 2'-PhCH₂), 4.70—4.67(m, 2H, 6'-PhCH₂), 4.65—4.62(m, 2H, 1-H), 4.58—4.56(m, 2H, 2COCHNH), 4.53—4.51(m, 1H, 3-H), 3.73—3.71(m, 1H, 5'-H), 3.60—3.56(m, 1H, 3'-H), 3.52—3.49(m, 1H, 2'-H), 3.48—3.46(m, 2H, 6'-H), 3.43—3.41(m, 1H, 4'-H), 2.32—2.28[m, 2H, 2CH(CH₃)₂], 2.27—2.23(m, 4H, 2NHCOCH₂), 1.69—1.65(m, 4H, 2CH₂), 1.31—1.28[m, 24H, 2(CH₂)₁₂], 0.92—0.88(m, 18H, 6CH₃)

Table 5 1H NMR and 13C NMR data of compounds 27—34

Compd.	¹H NMR(500 MHz, DMSO), δ	¹³C NMR(125 MHz, DMSO), δ
27	8.21—8.23(m, 2H, 2NH), 5.12—5.05(m, 1H, 1'-H),5.04—4.88(m, 1H, 2-H), 4.88—4.78(m, 2H, 1-H), 4.69—4.62(m, 2H, 1COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.38—4.36(m, 1H, 2'-H), 4.25—4.06(m, 2H, 1COCH₂NH), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.16—3.07(m, 2H, 6'-H), 2.11—2.09(m, 4H, 2NHC=OCH₂), 1.48—1.46(m, 4H, CH₂), 1.23—1.21(m, 24H, 12CH₂), 0.85—0.82(m, 6H, 2CH₃)	173.22(NHC=O), 173.19(NHC=O),169.47(C=O), 169.45(C=O), 95.15(C1'), 79.26(C2'), 78.31(C2), 76.59(C3'), 72.83(C4'), 69.72(C5'), 67.74(C3), 64.95(C1), 60.80(C6'), 35.46, 31.67, 29.42, 29.33, 29.20, 29.08, 28.96, 25.56, 22.46, 14.30
28	8.23—8.21(m, 2H, 2NH), 5.72—5.71(m, 1H, 2-H), 5.36—5.34(m, 1H, 1'-H), 5.27—5.26(m, 1H, 3'-OH), 5.11—5.10(m, 1H, 4'-OH), 5.02—5.01(m, 1H, 2'-OH), 4.63—4.60(m, 1H, 6'-OH), 4.39—4.37(m, 2H, 1-H), 4.25—4.21(m, 2H, 1COCH₂NH), 4.20—4.18(m, 1H, 4'-H), 3.90—3.87(m, 2H, 1COCH₂NH), 3.85—3.83(m, lH, 3-H), 3.81—3.73(m, 1H, 2'-H), 3.65—3.62(m, 1H, 5'-H), 3.47—3.43(m, 1H, 3'-H), 3.22—3.21(m, 2H, 6'-H), 2.24—2.13(m, 4H, 2NHC=OCH₂), 1.67—1.59(m, 4H, NHC=OCH₂CH₂), 1.26—1.25(m, 32H, 16CH₂), 0.89—0.86(m, 6H, 2CH₃)	173.53(NHC=O), 173.42(NHC=O),171.53(C=O), 171.52(C=O), 95.67(C1'), 78.64(C2'), 78.59(C2), 76.94(C3'), 73.30(C4'), 73.19(C5'), 70.16(C3), 61.25(C1), 56.92(C6'), 39.48, 35.83, 35.76, 32.08, 29.82, 29.73, 29.60, 29.48, 29.36, 29.33, 25.97, 22.87(CH₂), 17.69, 14.68(CH₃)
29	8.25—8.24(m, 2H, 2NH), 5.12—5.05(m, 1H, 1'-H), 4.96—4.94(m, 1H, 2-H), 4.89—4.87(m, 2H, 1-H), 4.78—4.70(m, 2H, 1COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.44—4.39(m, 1H, 2'-H), 4.25—4.06(m, 1H, 1COCH₂NH), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.15—3.05(m, 2H, 6'-H), 2.09—2.06(m,	173.29(NHC=O), 173.24(NHC=O), 169.55(C=O), 169.50(C=O), 95.24(C1'),79.55(C2'), 78.41(C2), 76.70(C3'), 72.93(C4'), 70.25(C5'), 68.82(C3), 60.90(C1), 56.96(C6'), 35.55, 31.76,
29	4H, 2NHC=OCH₂), 1.46—1.45(m, 4H, CH₂), 1.28—1.25(m, 40H, 20CH₂), 0.84—0.82(m, 6H, 2CH₃)	29.52, 29.47, 29.41, 29.29, 29.16, 29.06, 25.65, 22.55, 14.41
30	8.21—8.23(m, 2H, 2NH), 5.11—5.03(m, 1H, 1'-H), 4.95—4.93(m, 1H, 2-H), 4.82—4.70(m, 2H, 1-H), 4.69—4.62(m, 4H, 2COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.38—4.36(m, 1H, 2'-H), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.16—3.07(m, 2H, 6'-H), 2.11—2.09(m, 4H, 2CH₂), 1.48—1.46(m, 4H, CH₂), 1.23—1.21(m, 48H, 24CH₂), 0.85—0.82(m, 6H, 2CH₃)	173.29(NHC=O), 173.24(NHC=O), 169.54(C=O), 169.22(C=O), 95.24(C1'),80.01(C2'), 78.40(C2), 76.68(C3'), 72.92(C4'), 69.82(C5'), 68.57(C3), 60.89(C1), 56.77(C6'), 35.55, 31.76, 29.52, 29.47, 29.41, 29.29, 29.16, 29.06, 25.65, 22.55, 14.41
31	8.25—8.20(m, 2H, 2NH), 5.58—5.51(m, 1H, 1'-H), 5.34—5.30(m, 1H, 2-H), 5.25—5.22(m, 1H, 3'-OH), 5.21—5.12(m, 1H, 6'-OH), 5.03—5.02(m, 1H, 2'-OH), 4.68—4.66(m, 1H, 4'-OH), 4.58—4.41(m, 2H, 1-H), 3.91—4.06(m, 2H, 2COCHN), 3.65—3.63(m, 1H, 4'-H), 3.46—3.44(m, 1H, 2'-H), 3.19—3.17(m, 1H, 5'-H), 3.16—3.14(m, 1H, 3'-H), 3.12—3.09(m, 2H, 6'-H), 2.23—2.12(m, 6H, 2CH, 2CH₂), 1.60—1.61(m, 4H, CH), 1.28—1.21(m, 24H, 12CH₂), 0.91—0.86(m, 18H, 6CH₃)	173.71(NHC=O), 173.57(NHC=O), 172.93(C=O), 172.69(C=O), 96.08(C1'),80.08(C2'), 79.10(C2), 77.38(C3'), 73.65(C4'), 70.55(C5'), 61.67(C3), 57.26(C1), 48.38(C6'), 36.14, 32.44, 30.07, 29.98, 29.84, 29.74, 29.70, 26.53, 26.33, 23.27(CH₂),18.16, 18.13 15.10(CH₃)
32	8.29—8.24(m, 2H, 2NH), 5.63—5.62(m, 1H, 1'-H), 5.38—5.36(m, 1H, 2-H), 5.29—5.28(m, 1H, 3'-OH), 5.24(s, 1H, 6'-OH), 5.16(s, 1H, 2'-OH), 5.07(s, 1H, 4'-OH), 4.70—4.42(m, 2H,1-H), 4.20(s, 1H, 4'-H), 4.17—4.15(m, 1H, 3a-H), 4.11—4.09(m, 1H, 2'-H), 3.95—3.87(m, 1H, 3b-H), 3.80—3.75(m, 1H, 3'-H), 3.49—3.47(m, 2H, 2COCHNH), 3.29—3.25(m, 1H, 5'-H), 3.18—3.16(m, 2H, 6'-H), 2.26—2.15(m, 6H, 2CH, 2CH₂), 1.60—1.62(m, 4H, 2CH₂), 1.28—1.25(m, 32H, 16CH₂), 0.92—0.87(m, 18H, 6CH₃)	173.72(NHC=O), 173.58(NHC=O), 172.82(C=O), 172.59(C=O), 95.97(C1'),80.09(C2'), 78.92(C2), 77.25(C3'), 73.48(C4'), 70.51(C5'), 61.60(C3), 57.16(C1), 48.20(C6'), 36.10, 32.34, 30.07, 30.06, 29.98, 29.84, 29.76, 29.58, 26.24, 23.14, 19.50, 18.02, 14.99
33	8.24—8.19(m, 2H, 2NH), 5.81—5.62(m, 1H, 1'-H), 5.33—5.30(m, 1H, 2-H), 5.25—5.24(m, 1H, 3'-OH), 5.21—5.20(m, 1H, 6'-OH), 5.12—5.10(m, 1H, 2'-OH), 4.67—4.65(m, 1H, 4'-OH), 4.57—4.56(m, 2H, 1-H), 4.30—4.28(m, 1H, 1H, 4'-H), 4.10—4.04(m, 2H, 3-H), 4.01—3.83(m, 2H, 2COCHNH), 3.65—3.63(m, 1H, 2'-H), 3.45—3.43(m, 1H, 5'-H), 3.21—3.20(m, 1H, 3'-H), 3.12—3.11(m, 2H, 6'-H), 2.16—2.06(m, 6H, 2CH, 2CH₂), 1.54—1.56(m, 4H, 2CH₂), 1.25—1.22(m, 40H, 20CH₂), 0.84—0.79(m, 18H, 6CH₃)	173.62(NHC=O), 173.45(NHC=O), 173.05(C=O), 172.78(C=O), 96.23(C1'),81.25(C2'), 79.24(C2), 77.56(C3'), 73.89(C4'), 70.50(C5'), 61.84(C3), 57.33(C1), 48.55(C6'), 36.35, 36.26, 32.59, 30.33, 30.24, 30.11, 30.00, 29.87, 26.47, 23.38, 19.82, 18.36, 18.32, 14.73(CH₃)
34	8.23—8.20(m, 2H, 2NH), 5.57—5.49(m, 1H, 1'-H), 5.30—5.24(m, 1H, 2-H), 5.22—5.21(m, 1H, 3'-OH), 5.11—5.02(m, 1H, 6'-OH), 4.68—4.66(m, 1H, 2'-OH), 4.58—4.56(m, 1H, 4'-OH), 4.38—4.30(m, 1H, 2-H), 4.12—4.05(m, 2H, 1-H), 3.98—3.82(m, 2H, 2CH), 3.65—3.64(m, 1H, 4'-H), 3.46—3.44(m, 1H, 2'-H), 3.22—3.21(m, 1H, 5'-H), 3.19—3.16(m, 1H, 3'-H), 3.12—3.09(m, 2H, 6'-H), 2.23—2.19(m, 2H, 2CH, 2.19—2.12(m, 4H, 2CH₂), 1.61—1.60(m, 4H, 2CH₂), 1.28—1.20(m, 48H, 24CH₂), 0.82—0.93(m, 18H, 6CH₃)	173.56(NHC=O), 173.45(NHC=O), 172.58(C=O), 172.36(C=O), 95.70(C1'),81.32(C2'), 78.62(C2), 76.96(C3'), 73.27(C4'), 70.24(C5'), 61.84(C3), 56.95(C1), 48.08(C6'), 35.85, 35.78, 32.10, 29.85, 29.76, 29.62, 29.51, 29.39, 29.35, 25.99, 22.90, 19.19, 17.71 14.70

Table 5 1H NMR and 13C NMR data of compounds 27—34

Compd.	¹H NMR(500 MHz, DMSO), δ	¹³C NMR(125 MHz, DMSO), δ
27	8.21—8.23(m, 2H, 2NH), 5.12—5.05(m, 1H, 1'-H),5.04—4.88(m, 1H, 2-H), 4.88—4.78(m, 2H, 1-H), 4.69—4.62(m, 2H, 1COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.38—4.36(m, 1H, 2'-H), 4.25—4.06(m, 2H, 1COCH₂NH), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.16—3.07(m, 2H, 6'-H), 2.11—2.09(m, 4H, 2NHC=OCH₂), 1.48—1.46(m, 4H, CH₂), 1.23—1.21(m, 24H, 12CH₂), 0.85—0.82(m, 6H, 2CH₃)	173.22(NHC=O), 173.19(NHC=O),169.47(C=O), 169.45(C=O), 95.15(C1'), 79.26(C2'), 78.31(C2), 76.59(C3'), 72.83(C4'), 69.72(C5'), 67.74(C3), 64.95(C1), 60.80(C6'), 35.46, 31.67, 29.42, 29.33, 29.20, 29.08, 28.96, 25.56, 22.46, 14.30
28	8.23—8.21(m, 2H, 2NH), 5.72—5.71(m, 1H, 2-H), 5.36—5.34(m, 1H, 1'-H), 5.27—5.26(m, 1H, 3'-OH), 5.11—5.10(m, 1H, 4'-OH), 5.02—5.01(m, 1H, 2'-OH), 4.63—4.60(m, 1H, 6'-OH), 4.39—4.37(m, 2H, 1-H), 4.25—4.21(m, 2H, 1COCH₂NH), 4.20—4.18(m, 1H, 4'-H), 3.90—3.87(m, 2H, 1COCH₂NH), 3.85—3.83(m, lH, 3-H), 3.81—3.73(m, 1H, 2'-H), 3.65—3.62(m, 1H, 5'-H), 3.47—3.43(m, 1H, 3'-H), 3.22—3.21(m, 2H, 6'-H), 2.24—2.13(m, 4H, 2NHC=OCH₂), 1.67—1.59(m, 4H, NHC=OCH₂CH₂), 1.26—1.25(m, 32H, 16CH₂), 0.89—0.86(m, 6H, 2CH₃)	173.53(NHC=O), 173.42(NHC=O),171.53(C=O), 171.52(C=O), 95.67(C1'), 78.64(C2'), 78.59(C2), 76.94(C3'), 73.30(C4'), 73.19(C5'), 70.16(C3), 61.25(C1), 56.92(C6'), 39.48, 35.83, 35.76, 32.08, 29.82, 29.73, 29.60, 29.48, 29.36, 29.33, 25.97, 22.87(CH₂), 17.69, 14.68(CH₃)
29	8.25—8.24(m, 2H, 2NH), 5.12—5.05(m, 1H, 1'-H), 4.96—4.94(m, 1H, 2-H), 4.89—4.87(m, 2H, 1-H), 4.78—4.70(m, 2H, 1COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.44—4.39(m, 1H, 2'-H), 4.25—4.06(m, 1H, 1COCH₂NH), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.15—3.05(m, 2H, 6'-H), 2.09—2.06(m,	173.29(NHC=O), 173.24(NHC=O), 169.55(C=O), 169.50(C=O), 95.24(C1'),79.55(C2'), 78.41(C2), 76.70(C3'), 72.93(C4'), 70.25(C5'), 68.82(C3), 60.90(C1), 56.96(C6'), 35.55, 31.76,
29	4H, 2NHC=OCH₂), 1.46—1.45(m, 4H, CH₂), 1.28—1.25(m, 40H, 20CH₂), 0.84—0.82(m, 6H, 2CH₃)	29.52, 29.47, 29.41, 29.29, 29.16, 29.06, 25.65, 22.55, 14.41
30	8.21—8.23(m, 2H, 2NH), 5.11—5.03(m, 1H, 1'-H), 4.95—4.93(m, 1H, 2-H), 4.82—4.70(m, 2H, 1-H), 4.69—4.62(m, 4H, 2COCH₂NH), 4.60—4.51(m, 1H, 4'-H), 4.50—4.47(m, lH, 3-H), 4.38—4.36(m, 1H, 2'-H), 3.81—3.80(m, 1H, 5'-H), 3.59—3.58(m, 1H, 3'-H), 3.16—3.07(m, 2H, 6'-H), 2.11—2.09(m, 4H, 2CH₂), 1.48—1.46(m, 4H, CH₂), 1.23—1.21(m, 48H, 24CH₂), 0.85—0.82(m, 6H, 2CH₃)	173.29(NHC=O), 173.24(NHC=O), 169.54(C=O), 169.22(C=O), 95.24(C1'),80.01(C2'), 78.40(C2), 76.68(C3'), 72.92(C4'), 69.82(C5'), 68.57(C3), 60.89(C1), 56.77(C6'), 35.55, 31.76, 29.52, 29.47, 29.41, 29.29, 29.16, 29.06, 25.65, 22.55, 14.41
31	8.25—8.20(m, 2H, 2NH), 5.58—5.51(m, 1H, 1'-H), 5.34—5.30(m, 1H, 2-H), 5.25—5.22(m, 1H, 3'-OH), 5.21—5.12(m, 1H, 6'-OH), 5.03—5.02(m, 1H, 2'-OH), 4.68—4.66(m, 1H, 4'-OH), 4.58—4.41(m, 2H, 1-H), 3.91—4.06(m, 2H, 2COCHN), 3.65—3.63(m, 1H, 4'-H), 3.46—3.44(m, 1H, 2'-H), 3.19—3.17(m, 1H, 5'-H), 3.16—3.14(m, 1H, 3'-H), 3.12—3.09(m, 2H, 6'-H), 2.23—2.12(m, 6H, 2CH, 2CH₂), 1.60—1.61(m, 4H, CH), 1.28—1.21(m, 24H, 12CH₂), 0.91—0.86(m, 18H, 6CH₃)	173.71(NHC=O), 173.57(NHC=O), 172.93(C=O), 172.69(C=O), 96.08(C1'),80.08(C2'), 79.10(C2), 77.38(C3'), 73.65(C4'), 70.55(C5'), 61.67(C3), 57.26(C1), 48.38(C6'), 36.14, 32.44, 30.07, 29.98, 29.84, 29.74, 29.70, 26.53, 26.33, 23.27(CH₂),18.16, 18.13 15.10(CH₃)
32	8.29—8.24(m, 2H, 2NH), 5.63—5.62(m, 1H, 1'-H), 5.38—5.36(m, 1H, 2-H), 5.29—5.28(m, 1H, 3'-OH), 5.24(s, 1H, 6'-OH), 5.16(s, 1H, 2'-OH), 5.07(s, 1H, 4'-OH), 4.70—4.42(m, 2H,1-H), 4.20(s, 1H, 4'-H), 4.17—4.15(m, 1H, 3a-H), 4.11—4.09(m, 1H, 2'-H), 3.95—3.87(m, 1H, 3b-H), 3.80—3.75(m, 1H, 3'-H), 3.49—3.47(m, 2H, 2COCHNH), 3.29—3.25(m, 1H, 5'-H), 3.18—3.16(m, 2H, 6'-H), 2.26—2.15(m, 6H, 2CH, 2CH₂), 1.60—1.62(m, 4H, 2CH₂), 1.28—1.25(m, 32H, 16CH₂), 0.92—0.87(m, 18H, 6CH₃)	173.72(NHC=O), 173.58(NHC=O), 172.82(C=O), 172.59(C=O), 95.97(C1'),80.09(C2'), 78.92(C2), 77.25(C3'), 73.48(C4'), 70.51(C5'), 61.60(C3), 57.16(C1), 48.20(C6'), 36.10, 32.34, 30.07, 30.06, 29.98, 29.84, 29.76, 29.58, 26.24, 23.14, 19.50, 18.02, 14.99
33	8.24—8.19(m, 2H, 2NH), 5.81—5.62(m, 1H, 1'-H), 5.33—5.30(m, 1H, 2-H), 5.25—5.24(m, 1H, 3'-OH), 5.21—5.20(m, 1H, 6'-OH), 5.12—5.10(m, 1H, 2'-OH), 4.67—4.65(m, 1H, 4'-OH), 4.57—4.56(m, 2H, 1-H), 4.30—4.28(m, 1H, 1H, 4'-H), 4.10—4.04(m, 2H, 3-H), 4.01—3.83(m, 2H, 2COCHNH), 3.65—3.63(m, 1H, 2'-H), 3.45—3.43(m, 1H, 5'-H), 3.21—3.20(m, 1H, 3'-H), 3.12—3.11(m, 2H, 6'-H), 2.16—2.06(m, 6H, 2CH, 2CH₂), 1.54—1.56(m, 4H, 2CH₂), 1.25—1.22(m, 40H, 20CH₂), 0.84—0.79(m, 18H, 6CH₃)	173.62(NHC=O), 173.45(NHC=O), 173.05(C=O), 172.78(C=O), 96.23(C1'),81.25(C2'), 79.24(C2), 77.56(C3'), 73.89(C4'), 70.50(C5'), 61.84(C3), 57.33(C1), 48.55(C6'), 36.35, 36.26, 32.59, 30.33, 30.24, 30.11, 30.00, 29.87, 26.47, 23.38, 19.82, 18.36, 18.32, 14.73(CH₃)
34	8.23—8.20(m, 2H, 2NH), 5.57—5.49(m, 1H, 1'-H), 5.30—5.24(m, 1H, 2-H), 5.22—5.21(m, 1H, 3'-OH), 5.11—5.02(m, 1H, 6'-OH), 4.68—4.66(m, 1H, 2'-OH), 4.58—4.56(m, 1H, 4'-OH), 4.38—4.30(m, 1H, 2-H), 4.12—4.05(m, 2H, 1-H), 3.98—3.82(m, 2H, 2CH), 3.65—3.64(m, 1H, 4'-H), 3.46—3.44(m, 1H, 2'-H), 3.22—3.21(m, 1H, 5'-H), 3.19—3.16(m, 1H, 3'-H), 3.12—3.09(m, 2H, 6'-H), 2.23—2.19(m, 2H, 2CH, 2.19—2.12(m, 4H, 2CH₂), 1.61—1.60(m, 4H, 2CH₂), 1.28—1.20(m, 48H, 24CH₂), 0.82—0.93(m, 18H, 6CH₃)	173.56(NHC=O), 173.45(NHC=O), 172.58(C=O), 172.36(C=O), 95.70(C1'),81.32(C2'), 78.62(C2), 76.96(C3'), 73.27(C4'), 70.24(C5'), 61.84(C3), 56.95(C1), 48.08(C6'), 35.85, 35.78, 32.10, 29.85, 29.76, 29.62, 29.51, 29.39, 29.35, 25.99, 22.90, 19.19, 17.71 14.70

Table 6 Yield of compound 18 in the solvent H2O/DMF at different temperatures

m(H₂O)/m(DMF)	Yield(%)
m(H₂O)/m(DMF)	90 ℃	110 ℃	120 ℃	130 ℃
0.01	58.9	64.5	61.7	54.4
0.02	69.8	71.3	64.2	63.1
0.03	70.3	73.7	67.6	66.2
0.04	68.3	73.2	63.2	62.9
0.05	63.1	70.9	61.8	55.5
0.06	60.8	70.3	61.5	58.7

Fig.1 Stability of compound 29 in aqueous buffer solutions(pH=3—10) and rat plasma in vitro

Table 7 Anti-tumor activities of compounds 27—34 against cancer and normal cell lines*

Compd.	IC₅₀/(μmol·L^-1)
Compd.	MCF-7	HcpG-2	K562	HL7702	H9C2	EVC304
27	3.53	4.71	4.13	>100	>100	>100
28	4.35	4.57	5.79	>100	NT	>100
29	12.98	25.17	28.93	NT	>100	>100
30	27.81	34.73	41.32	>100	>100	NT
31	3.91	3.73	4.54	>100	NT	>100
32	5.17	5.52	5.93	NT	>100	NT
33	17.79	41.39	58.31	NT	>100	NT
34	37.57	>60	>60	>100	NT	NT

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