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Synthesis and biological evaluation of dehydroabietic acid- pyrimidine hybrids as antitumor agents

Lin Huanga, Rong Huanga，Fuhua Panga, Anke Lia, Guobao Huangb, Xiaoqun Zhoua*, Qian Lia*, Fangyao Lia,b,c*, Xianli Maa a School of Pharmacy, Guilin Medical University, Guilin, 541004, PR b Guangxi Key Lab of Agricultural Resources Chemistry and Biotechnology, College of Chemistry and Food Science, Yulin Normal University, Yulin, Guangxi 537000, PR China cState Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin, Gungxi 541006, PR China. 2 1

90 . 6 3 7 3 8 %T 4 0 9 . . 1 8 2 5 6 75 3 2 0 3 7 1 8 4 . 5 . 8 . 6 . 7 6 5 7 5 0 2 7 0 5 0 5 . 7 4 4 1 5 4 .

60 3 6 0 9 0 7 . 1 9 7 6 8 3 . . 0 9 4 45 3 1 9 8 5 4 . 0 3 8 5 3 1 . 2 9 1 8 7 7 . 9 8 1 1 2 1 1 5 . 7 1 5 . 30 6 0 . 2 1 6 9 . 7 4 2 2 1 1 5 4 1 7 1 2 8 1 6 . 3 9 . 2 4 9 8 2

15 2 2 7 . 1 2 7 6 1 0

4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S1. FTIR spectrum of the target compound (3a) 82 81 28 19 17 01 90 22 21 38 37 33 31 14 13 47 44 90 84 32 30 25 23 06 78 76 66 28 24 23 22 90 ...... 7 7 7 7 7 7 6 6 6 4 4 4 4 4 4 3 3 2 2 2 2 2 2 2 1 1 1 1 1 1 1 0 76 84 19 97 94 77 19 01 02 79 13 85 52 65 84 22 06 72 11 23 00 ...... 0 0 1 0 0 0 2 2 1 0 1 0 0 0 1 1 1 0 3 6 3

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 f1 (ppm) 1 Figure S2. H-NMR spectrum of the target compound (3a) in CDCl3 43 93 23 03 93 89 77 05 31 07 22 ...... 37 16 95 62 85 82 05 58 44 30 12 10 94 68 60 ...... 178 164 161 155 146 145 134 127 124 124 111 77 77 76 62 47 44 37 33 29 25 24 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S3. C-NMR spectrum of the target compound (3a) in CDCl3 Figure S4. HR-MS spectrum of the target compound (3a)

90 %T 75 4 2 . 6 2 3 . 5 9 7 0 5 9 2 5 . 1 60 7 . 2 4 . 8 8 7 1 2 4 7 7 6 . 0 6 0 4 5 2 . 3 9 3 . 2 8 0 3 8 8 4 5 6 0 . 3 5

45 . 7 1 3 . 6 2 7 6 8 3 9 0 1 0 0 . 4 1 4 30 2 3 8 . 7 6 7 8 0 8 . 8 0 3 5 0 7 . 1 . 2 8 1 . . 7 4 0 5 8 9 . 5 2 7 5 3 0 1 1 8 4 5 3 9 1 2 1 1 2 7

15 . 7 1 2 0 8 . 2 7 . 6 1 8 5 1 2 9 7 2 1 1 7 . 0

0 6 6 1

-15 4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S5. FTIR spectrum of the target compound (3b) 28 19 17 01 89 02 35 29 39 89 83 44 27 25 78 77 67 66 28 23 19 96 95 94 ...... 7 7 7 7 6 6 4 4 3 2 2 2 2 2 1 1 1 1 1 1 1 0 0 0 29 15 30 15 23 92 04 84 60 96 55 18 96 12 56 85 94 27 57 55 26 04 00 34 13 65 03 50 92 ...... 1 1 1 1 1 0 1 0 0 0 0 1 0 1 0 0 0 1 0 0 1 3 3 6 1 0 1 1 0

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 f1 (ppm) 1 Figure S6. H-NMR spectrum of the target compound (3b) in CDCl3 45 35 08 15 93 85 76 06 29 06 94 ...... 36 15 94 81 83 89 07 58 24 32 10 93 11 69 60 82 ...... 178 169 166 160 146 145 134 127 124 124 107 77 77 76 62 47 44 37 33 29 25 24 21 21 18 16 13

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S7. C-NMR spectrum of the target compound (3b) in CDCl3 Figure S8. HR-MS spectrum of the target compound (3b)

175 %T 0 3 4 2

150 . . 1 0 8 9 9 7 . 3 5 3 2 8 . 2 2 4 3 1 4 2 7 125 3 3 4 . 9 2 8 4 2 3 .

100 5 4 6 1 8 8 2 . 5 1 75 . 9 8 6 7 7 0 7 1 . . 5 7 8 4 3 . 2 9 8 8 6 5 2 7 7 . 1 . 4 0 7 2 6 4 .

50 3 7 5 3 5 9 . 6 5 2 0 2 8 8 2 . . 4 8 8 7 3 . 3 0 8 3 9 6 . 1 8 0 6 8 0 . 1 3 7 8 1 8

25 9 2 4 3 1 8 . 0 0 5 7 4 . 2 2 4 4 . 7 7 . 1 2 7 8 2 1 3 . 0 3 7 0 1 5 9 2 1 . 3 1 2 0 . 1 0 6 9 7 5 4 3 . 2 . 6 2 9 4 2 1 7 2 1 5 7 1 -25 1 4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm Figure S9. FTIR spectrum of the target compound (3c) 28 19 17 03 90 69 40 34 42 85 39 26 79 71 67 65 47 29 25 24 22 ...... 7 7 7 7 6 6 4 4 3 2 2 2 1 1 1 1 1 1 1 1 1 04 03 02 03 09 06 14 72 27 06 04 04 84 59 21 04 11 10 00 05 ...... 1 1 1 1 1 1 2 0 1 6 1 1 0 1 1 1 2 3 6 3

7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 f1 (ppm)

1 Figure S10. H-NMR spectrum of the target compound (3c) in CDCl3 54 30 23 00 80 89 08 30 04 96 ...... 38 17 96 39 84 86 08 59 57 36 11 96 93 74 63 ...... 178 170 167 147 145 134 127 124 124 115 77 77 76 63 47 44 37 33 29 25 24 23 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S11. C-NMR spectrum of the target compound (3c) in CDCl3 Figure S12. HR-MS spectrum of the target compound (3c)

110 %T 9 7 100 . 8 1 2 0 6 . 3 1 6 . 4 3 4 4 3 4 5

90 8 . 8 9 8 3 . 2 1 . 8 5 1 4 6 7 5 1 2 8 2 9 . . 8

80 5 . 8 1 0 7 6 3 . 3 3 1 0 8 1 8 8 1 . 4 3 8 6 4 3 0 6 7 . 6 8 5 3 8 7 . . . 2 70 2 3 4 2 1 6 8 5 0 1 3 . 4 5 8 9 2 6 0 1 9 . 2 . 4 2 7 4 2 . 6 4 1 2 4 5 7 1 1 6 60 1 3 1 . 4 4 2 1 7 . 2 1 9 7 4 . 6 2 1 5

50 8 2 6 1 . 2 2

40 9 2

30 4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm Figure S13. FTIR spectrum of the target compound (3d) 28 19 18 01 89 07 37 33 46 45 91 89 85 84 82 33 31 28 27 25 79 77 67 29 24 23 23 ...... 7 7 7 7 6 6 4 4 3 3 2 2 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 10 09 09 15 16 19 26 99 55 14 97 05 48 72 97 50 61 50 55 24 16 34 00 ...... 1 1 1 1 1 1 1 0 0 1 0 2 3 0 0 0 0 0 0 1 3 6 3

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 f1 (ppm) 1 Figure S14. H-NMR spectrum of the target compound (3d) in CDCl3 42 05 44 66 94 85 79 06 30 06 59 ...... 37 16 95 71 85 87 07 58 36 33 26 12 09 94 69 60 ...... 178 166 165 159 146 145 134 127 124 124 108 77 77 76 62 47 44 37 33 29 25 24 24 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S15. C-NMR spectrum of the target compound (3d) in CDCl3 Figure S16. HR-MS spectrum of the target compound (3d)

120 %T 2 7 . 0

105 1 3 2 7 2 7 . 9 8 . 6 9 6 9 3 90 9 . 7 0 2 3 9 6 . 6 7 0 9 4 7 . . 3 6 9 5 8 6 3 3 0 1 75 1 2 7 9 . 8 3 2 . 2 7 . 5 2 4 1 1 4 1 0 1 . . 1 9 3 8 . 8 8 5 4 0 6 1 0 60 2 8 2 1 . 0 2 2 2 4 2 . 1 6 8 5 . 4 1 0 2 8 0 1 6 . 5 8 2 1 6 . 7 3 9 0 1 . 1 8 . 2 . 4 6 6 6

45 9 5 7 1 4 5 2 9 8 2 3 3 9 . 2 . 1 4 2 5 . 6 0 2 1 3 2 6 1 9 7 1 0 1 30 . 7 4 5 3 3 4 7 8 . . 0 5 8 0 7 4 . 6

15 4 5 4 7 3 1 . 1 9 4 6 3 4 1 0 4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm Figure S17. FTIR spectrum of the target compound (3e) 03 62 61 28 14 01 99 90 85 26 19 67 20 97 90 81 28 26 20 56 44 31 ...... 8 7 7 7 7 7 6 6 6 4 4 3 3 2 2 2 2 2 2 1 1 1 38 36 12 15 08 35 26 51 34 51 93 14 26 02 15 62 60 07 19 05 00 ...... 2 2 1 1 1 1 1 0 2 0 0 3 1 1 1 0 0 1 3 6 3

8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 f1 (ppm) 1 Figure S18. H-NMR spectrum of the target compound (3e) in CDCl3 64 77 21 68 81 90 63 07 07 28 10 26 ...... 19 36 15 94 37 10 61 76 89 01 56 28 26 11 93 65 59 ...... 178 170 166 162 146 145 131 127 126 124 124 119 90 77 77 76 66 63 61 47 44 37 33 29 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S19. C-NMR spectrum of the target compound (3e) in CDCl3 Figure S20.HR-MS spectrum of the target compound (3e)

90 %T 0 8 80 9 . 8 . 4 9 3 9 0 8 2 0 1 8 .

70 2 6 3 2

60 4 5 . 6 0 9 4 9 .

50 0 4 6 4 7 2 . 8 2 6 2 . . 7 4 8 4 0 6 6 3 5 7 3 . 4 9 3 3 5 . 4 .

40 1 5 9 2 4 . 2 0 1 5 1 2 3 . 5 5 3 4 . 9 3 4 2 2 3 1 3 2 3 2 7 3 8 0 9 8 . . 2 0 3 . 30 0 4 1 . . 1 7 4 8 2 0 9 6 8 3 . 0 7 7 1 5 1 4 8 8 0 7 . 0 . 2 8 2 0 5 8 1 7 9 1 1 1 8 7 . . . 6 1 20 8 0 1 5 . 1 1 0 6 0 9 6 1 6 3 2 1 1 3 1 9 . 1 2 4 4 0 2 . 3 7 6 .

10 8 1 0 8 9 5 3 . 1 2 4 1 6 4 7 5 . 1 9

0 6 4 1 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S21. FTIR spectrum of the target compound (3f) 76 75 74 28 15 13 00 99 88 87 86 83 39 23 16 87 16 96 89 79 27 25 18 16 68 66 55 42 23 21 20 19 15 ...... 7 7 7 7 7 7 7 6 6 6 6 6 4 4 4 3 3 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 57 03 06 07 41 00 83 25 38 16 03 04 10 00 ...... 0 1 1 1 2 1 2 7 2 3 1 6 3 3

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) 1 Figure S22. H-NMR spectrum of the target compound (3f) in CDCl3 74 34 41 10 56 81 91 56 99 93 10 29 46 32 ...... 76 36 15 94 17 77 90 00 56 08 24 08 07 89 63 52 ...... 178 171 166 165 163 146 145 134 130 130 124 119 115 115 89 77 77 76 63 47 44 37 33 29 25 24 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S23. C-NMR spectrum of the target compound (3f) in CDCl3 Figure S24. HR-MS spectrum of the target compound (3f)

120

%T 0 9 . 1 4 7 3

105 2 6 . 4 1 3 2 2 2 . 0 3 . 6 9 1 4 2 5 2 7 3

90 4 . 0 2 0 1 1 4 6 8 . . . 8 3 6 3 8 7 2 7 4 6 8 7 8 4 7 . 8 7 0 8 . . 9 . 2 9 . 5 2 6 6 0 6 3 1 . 3 75 2 7 0 4 8 5 1 6 0 1 3 9 3 . 1 2 6 5 1 2 1 0 1 7 . 6 . 5 . 8 1 2 7 4 6 7 0 2 . 8 1 1 8 2 1 1 60 7 6 1 7 2 5 . 9 7 7 . 3 9 4 . 9 5 5 3 0 1 9 . 6 2 4 4 4

45 1 2 1 6 3 . 4 2 7 30 1

3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S25. FTIR spectrum of the target compound (3g) 39 30 28 15 13 04 99 84 23 17 68 14 09 93 81 78 24 17 15 68 61 52 42 22 21 15 ...... 7 7 7 7 7 7 6 6 4 4 3 3 3 2 2 2 2 2 2 1 1 1 1 1 1 1 20 54 20 27 34 14 77 56 51 52 13 24 98 19 55 42 00 12 21 ...... 1 0 1 1 2 1 2 2 0 0 1 1 1 1 1 1 3 3 6

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 f1 (ppm) 1 Figure S26. H-NMR spectrum of the target compound (3g) in CDCl3 28 51 44 94 76 87 81 69 00 02 19 01 ...... 33 36 15 94 58 78 84 03 99 52 57 15 74 23 10 79 62 41 ...... 179 173 173 164 158 146 145 134 131 124 119 116 92 77 77 76 63 47 44 38 36 36 33 30 28 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S27. C-NMR spectrum of the target compound (3g) in CDCl3 Figure S28. HR-MS spectrum of the target compound (3g)

82.5 %T 8 7 6 4 .

75 . 1 1 2 8 8 8 0 4 8 2 . . 3 67.5 7 9 1 6 0 7 9 1 1 1 1 . . 2 0 6 7 5 2 . 8 5 8 4 1 3 2 . 3 7 . 2 0 7 5 3 2 5 . . 1 1 2 7 4 5 1 0 . 1 2 60 . 0 0 8 0 2 3 1 1 3 8 2 1 1 2 6 1

52.5 3 8 . 3 1 4 0 7 . 6 3 2 0 3 7 9 . . 8 4 5 45 2 2 6 4 7 1 4 9 . 7 1 4 1 . 7 8 . 3 4 1 9 3 2 2 2 5 . 1 9 1 4 2 37.5 7 6 1 8 5 . 30 9 9 7 . 7 9 4 1 3 4 22.5 3

4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S29. FTIR spectrum of the target compound (3h) 04 46 45 28 17 16 02 00 88 37 33 89 82 43 98 91 85 31 29 23 21 73 63 48 40 26 23 20 18 ...... 8 7 7 7 7 7 7 7 6 4 4 3 3 3 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 82 31 17 54 39 86 14 33 96 95 57 93 08 91 83 15 24 08 15 06 ...... 0 1 1 0 1 0 1 2 2 1 2 2 1 0 1 1 1 3 6 3

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 f1 (ppm) 1 Figure S30. H-NMR spectrum of the target compound (3h) in CDCl3 48 77 98 90 12 89 86 51 07 18 26 05 75 47 66 ...... 10 38 17 95 53 46 84 88 75 66 28 10 92 64 59 ...... 178 167 165 162 157 146 145 130 127 125 124 124 120 115 111 97 77 77 76 62 55 47 44 36 31 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S31. C-NMR spectrum of the target compound (3h) in CDCl3 Figure S32. HR-MS spectrum of the target compound (3h)

135 %T 120 0 6 3 . 8 . 6 6 7 5 0 3 5 3 2 . 2 1 8 5 0 7

105 . 3 0 7 8 4 2 6 . 4 0 2

90 2 5 0 9 8 . . 2 4 7 1 1 5 4 . 6 3 . 9 9 2 5 7 9 8 . 2 3 7 7 2 0 . 1 . 9 9 1 4 8 7 5 0 0 4 3 9 1 0 5

75 . 1 . 1 3 1 1 4 0 . 2 3 6 4 1 2 1 3 1 8 0 . 3 5 1 2 . 5 4 6 . . 5 8 3 2 4 4 7 7 2 7 . 7 60 6 7 1 1 8 1 . 6 1 1 1 6 1 7 . 2 4 2 6 1 4 . 2 5 1 6 0 5 7 7 7 . . 8 45 0 5 6 5 0 1 4 5 . 9 . 1 4 5 6 6 4 4 3 1 30 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S33. FTIR spectrum of the target compound (3i) 02 24 19 14 12 10 97 82 25 18 88 83 63 27 13 95 88 79 25 14 79 68 24 21 17 87 ...... 8 7 7 7 7 7 6 6 4 4 3 3 3 3 3 2 2 2 2 2 1 1 1 1 1 0 53 96 95 90 70 93 30 09 01 17 06 07 09 00 16 17 78 14 01 17 ...... 0 0 0 0 0 0 1 2 3 3 2 3 1 1 2 1 0 6 3 3

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) 1 Figure S34. H-NMR spectrum of the target compound (3i) in CDCl3 81 35 42 74 26 86 81 68 67 04 01 99 86 42 ...... 59 37 16 94 58 24 71 87 61 56 09 23 10 85 64 51 ...... 178 172 167 162 159 146 145 137 134 127 124 120 116 113 89 77 77 76 63 55 47 44 36 31 29 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S35. C-NMR spectrum of the target compound (3i) in CDCl3 Figure S36. HR-MS spectrum of the target compound (3i)

175 %T 1 0 1 5 4 . . 4 . 0 3 1 7 150 6 8 7 3 5 3 6 2 2 . 2 6 8 8 9 1 6 . 0

125 4 0 2 3 5 . 4 7

100 0 3 2

75 2 . 6 6 8 2 4 6 . 4 0 8 50 0 8 4 2 . . 6 2 1 8 9 3 8 3 . 9 1 2 2 . 2 3 8 2 2 3 8 9 6 . 6 2 1 9 8 3 . 0 5 7 . 3

25 . 1 9 2 5 1 4 3 . 4 2 . 3 8 0 2 . 1 2 1 0 2 2 0 1 0 0 9 4 3 2 . 1 2 . 2 5 1 4 0 1 1 2 . 7 . 4 7 9 . 3 8 1 7 9 5 8 9 1 4 2 7 . . . 6 3 6 3 7 5 1 0 4 9 3 5 7 1 5 1 3 6 0 . . 8 2 6 5 1 1 1 . 0 2 5 5

0 6 2 . 1 7 7 1 4 7 4 4 1 4 3 4 1 3

3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S37. FTIR spectrum of the target compound (3j) 00 72 28 13 11 98 97 82 67 66 22 15 66 10 06 94 87 79 78 22 16 14 66 52 51 41 25 21 19 15 12 ...... 8 7 7 7 7 6 6 6 6 6 4 4 3 3 3 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 28 04 10 05 24 14 14 11 01 98 27 33 09 59 97 04 80 86 99 21 28 57 08 11 09 00 ...... 2 1 1 1 2 1 1 3 1 0 1 1 1 0 0 1 0 0 0 1 1 0 3 3 3 3

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 f1 (ppm) 1 Figure S38. H-NMR spectrum of the target compound (3j) in CDCl3 94 75 92 77 51 86 78 69 30 05 23 97 51 ...... 02 36 14 93 66 20 71 89 61 56 81 23 08 83 64 45 ...... 178 174 166 162 161 146 145 134 130 127 124 123 113 88 77 77 76 63 55 47 44 36 31 28 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S39. C-NMR spectrum of the target compound (3j) in CDCl3 Figure S40. HR-MS spectrum of the target compound (3j)

90 %T 8 6 . 6

75 8 9 1 1 5 . 6 1 3 60 2 2 9 . 2 6 4

45 1 0 . 3 1 9 3 4 . 8 4 9 7 . 3 0 9 8 . 5 9 5 8 7 5 7 6 9 30 7 . . 9 8 8 9 2 8 . 3 6 4 1 2 1 5 4 8 2 5 . 8 8 6 . 15 . 6 0 9 7 3 1 0 8 1 3 . . 1 7 8 0 9 4 6 1 6 8 . 2 3 7 1 1 6 5 8 7 3 1 8 3 6 . 9 . 0 7 4 . 5 8 . . 4 0 7 0 7 6 . 9 6 8 6 9 8 1 . 0 6 . . 6 8 5 2 4 4 9 0 1 1 7 4 0 2 6 1 . 1 5 2 1 0 2 2 6 1 1 2 . . 9 9 2 1 9 9 1 2 2 1 4 3 6 1 5 7 1 -15 1

3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S41. FTIR spectrum of the target compound (3k) 06 94 77 34 29 18 09 01 88 55 43 84 49 43 98 92 83 33 31 25 23 79 68 31 23 22 97 88 ...... 8 7 7 7 7 7 7 7 6 4 4 3 3 3 2 2 2 2 2 2 2 1 1 1 1 1 0 0 84 06 21 21 35 31 30 31 38 19 17 38 42 52 09 98 21 11 19 18 19 20 23 00 ...... 0 1 1 1 1 1 1 1 1 1 1 2 2 0 1 0 1 1 1 2 1 3 3 6

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 f1 (ppm) 1 Figure S42. H-NMR spectrum of the target compound (3k) in CDCl3 48 26 16 05 72 98 46 52 14 07 27 17 80 18 79 ...... 31 38 16 95 45 06 01 06 79 35 27 09 94 62 64 ...... 179 167 163 157 146 145 135 134 130 127 124 124 120 120 116 93 77 77 76 62 48 45 37 31 29 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S43. C-NMR spectrum of the target compound (3k) in CDCl3 Figure S44. HR-MS spectrum of the target compound (3k)

105 %T 90 1 0 . 6 1 9 8 4 . 8 4 4 . 6 3 0 5 0 . 6 75 2 4 3 5 2 0 3 3 9 3 4 . . 9 3 2 7 5 6 . 5 4 8 5 6 3

60 2 9 7 7 8 . . 1 0 6 0 5 8 7 6 . 8 6 . 0 8 0 8 1

45 9 1 5 . 2 6 8 9 8 . 4 8

30 3 1 5 8 7 . 1 3 5 . 4 3 7 7 3 . 7 0 7 2 . 9 . 1 3 5 1 5 8 1 6 8 1 0

15 . 7 0 8 6 1 6 6 1 8 . 8 . 9 2 9 6 8 7 0 0 6 . 3 6 8 7 2 . . . 4 1 1 8 9 6 4 1 2 2 0 2 2 7 0 3 1 9 6 1 6 9 4 0 1 . . . 6 2 1 2 0 3 5 3 . . 0 6 9 9 4 5 4 6 3 2 1 1 1 5 7 1 -15 1

3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S45. FTIR spectrum of the target compound (3l) 38 06 65 33 02 88 48 44 57 98 91 86 82 31 29 27 25 78 71 68 46 29 23 22 21 ...... 8 8 7 7 7 6 4 4 3 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 25 54 26 33 35 45 41 09 62 80 71 78 80 21 23 12 00 ...... 1 0 1 1 1 1 1 3 2 1 2 2 2 3 3 3 3

9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) 1 Figure S46. H-NMR spectrum of the target compound (3l) in CDCl3 40 95 10 46 85 88 93 65 06 11 36 ...... 38 17 95 49 46 88 93 05 67 08 31 09 07 99 68 62 ...... 178 162 160 154 146 145 134 134 127 124 117 77 77 76 62 61 47 44 37 31 30 25 24 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S47. C-NMR spectrum of the target compound (3l) in CDCl3 Figure S48. HR-MS spectrum of the target compound (3l)

225 %T 200

175 0 9 . 1 4

150 7 3 4 4 . 2 7 3

125 2 7 0 . 0 2 2 8 2

100 0 . 0 7 8 2 9 9 7 . 75 6 . 6 6 0 9 8 4 4 8 2 . 2 4 . 3 . 9 9 3 1 6 5 7 6 . 3 5 4 6 3 9 9 . 9 8 6 . 9 1 3 2 50 9 1 1 7 9 9 2 0 . 0 9 . 8 5 3 1 8 3 . 4 3 4 . 9 6 7 . 5 1 6 4 1 1 2 2 4 . 4 . . 2 5 3 7 6 1 8 0 6 8 4 2 8 1 6 1 5 5 25 7 1 1 1 . 2 . 7 2 6 1 3 4 3 5 . 9 . 2 6 3 5 4 . 1 6 1 2 4 2 7 0 7 1 1 1 1 -25 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S49. FTIR spectrum of the target compound (3m) 16 03 99 97 28 17 16 02 00 99 86 51 40 38 28 27 26 82 97 90 84 83 29 24 78 77 42 41 40 31 29 24 23 21 ...... 8 8 7 7 7 7 7 7 7 6 6 4 4 4 4 4 4 3 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 92 81 66 47 07 27 28 12 22 37 08 91 02 11 00 ...... 0 1 1 1 1 3 1 2 3 4 1 2 3 6 3

11.0 10.5 10.0 9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 f1 (ppm) 1 Figure S50. H-NMR spectrum of the target compound (3m) in CDCl3 55 18 77 39 91 91 69 73 09 25 38 ...... 84 38 17 95 39 31 88 85 04 57 17 26 10 89 67 61 ...... 178 163 162 154 146 145 134 133 124 116 115 99 77 77 76 66 66 47 44 37 33 30 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S51. C-NMR spectrum of the target compound (3m) in CDCl3 Figure S52. HR-MS spectrum of the target compound (3m) 8 4 7 .

90 1 . 0 5 2 6 5 %T 5 8 7 9 . 8 2 . 5 7 7 5 6 7 . 4 3 2 9 . . 75 4 6 8 4 4 0 9 0 7 0 9 6 6 7 . . 4 3 0 1 2 0 1 . 8 7 0 8 . 1 3 1 7 0 2 5 3 5 . 3 2 3 0 9 1 8 . 60 . . 9 1 8 8 6 1 3 5 0 3 1 . 0 . 4 1 6 0 3 2 7 2 1 6 1 1 3 7 5 4 4 . 3 6 3 2 . 7 0 1 2 1 1

45 1 8 0 . 0 0 5 9 . 7 0 4 3 8 . 2 0 9 2 4 . 9 6 4 8 . 5 0 1 2 4 5 9 8

30 . 1 3 6 . 6 4 1 4 1 3 5 1 3 . 9 9 4 2 2 2 7 1 1 4 .

15 3 3 5 1

0

4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm

Figure S53. FTIR spectrum of the target compound (3n) 71 26 22 05 52 28 18 15 14 01 90 84 34 28 83 38 99 91 82 27 20 17 80 72 44 37 31 25 24 22 21 19 17 ...... 8 8 8 8 7 7 7 7 7 7 6 6 4 4 3 3 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 1 1 77 81 58 88 64 91 79 67 31 11 39 53 64 71 75 47 04 90 82 93 27 02 06 08 00 ...... 0 0 0 0 0 0 0 0 1 1 1 0 0 0 0 1 1 0 0 0 1 2 6 3 3

9.5 9.0 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 f1 (ppm) 1 Figure S54. H-NMR spectrum of the target compound (3n) in CDCl3 58 23 16 93 80 91 85 54 83 07 03 98 30 12 80 ...... 37 16 95 39 54 63 84 88 01 55 73 24 10 92 69 55 ...... 178 165 148 146 146 145 136 134 129 127 127 125 124 124 123 77 77 76 66 62 61 47 44 37 33 29 25 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S55. C-NMR spectrum of the target compound (3n) in CDCl3 Figure S56. HR-MS spectrum of the target compound (3n)

160 %T 0

140 9 . 1 4 7 3 1 0 .

120 1 3 4 2 4 . 3 8 7 3 100 2 5

80 1 . 8 6 9 9 8 4 5 1 . . 2 2 9 6 8 . 0 0 9 8 7 6 0 0 0 7 . . . 9 8 3 2 6 . . 4 9 8 9 9 1 2 8 6 9 7 9 2 5 . 6 8 . 0

60 4 2 0 6 6 4 5 . 9 7 5 1 9 0 7 . . 8 0 2 3 3 3 1 2 4 . 4 . 0 9 4 0 6 0 1 2 7 1 . 8 2 0 1 0 5 1 7 7 2 . . 9 . 1 1 7 3 2 3 6 0 8 . 1 7 5 9 7 4 1 6 2 1 4

40 1 1 1 2 1 8 9 . 4 4 4

20 0 . 5 2 1 6 4 1 0 4000 3500 3000 2500 2000 1750 1500 1250 1000 750 500 1/cm Figure S57. FTIR spectrum of the target compound (3o) 03 92 74 28 14 00 84 60 29 23 55 25 96 89 80 43 31 18 70 57 36 20 16 ...... 8 7 7 7 7 7 6 4 4 4 3 3 2 2 2 2 2 2 1 1 1 1 1 16 95 09 16 98 73 31 30 84 03 13 09 35 12 80 06 03 00 ...... 2 0 2 1 0 0 2 2 0 1 3 1 3 1 1 3 6 3

8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 f1 (ppm) 1 Figure S58. H-NMR spectrum of the target compound (3o) in CDCl3 75 78 28 88 81 17 57 12 80 25 02 42 ...... 37 16 94 18 39 77 90 02 56 22 27 10 08 60 65 52 ...... 178 167 159 146 145 143 141 133 128 124 124 115 77 77 76 63 49 47 44 37 33 29 25 24 24 21 18 16

230 220 210 200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 f1 (ppm) 13 Figure S59. C-NMR spectrum of the target compound (3o) in CDCl3 Figure S60. HR-MS spectrum of the target compound (3o)