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UFRRJ

INSTITUTO DE CIÊNCIAS EXATAS

PROGRAMA DE PÓS-GRADUAÇÃO EM QUÍMICA

D

ISSERTAÇÃO

Síntese de novos naftoimidazóis derivados de



-lapachona

com potenciais atividades biológicas.

LEONARDO ARAUJO SILVA

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Sumário

Espectro 1. RMN-1H (400 MHz, DMSO-d6) do BLI-H (1). ... 10

Espectro 2. EM-IES do composto 37a. ... 11

Espectro 3. RMN-1H (500 MHz, CDCl3)do composto 37a. ... 12

Espectro 4. DEPTQ (500 MHz, CDCl3) do composto 37a. ... 13

Espectro 5. 1H-COSY (500 MHz, CDCl3) do composto 37a. ... 14

Espectro 6. HSQC (500 MHz, CDCl3) do composto 37a. ... 15

Espectro 7.HMBC (500 MHz, CDCl3) do composto 37a. ... 16

Espectro 8. NOESY (500 MHz, CDCl3) do composto 37a. ... 17

Espectro 9. EM-IES (500 MHz, CDCl3) do composto 37b. ... 18

Espectro 10. RMN-1H (500 MHz, CDCl3) do composto 37b. ... 19

Espectro 11. RMN-13C (125 MHz, CDCl3) do composto 37b. ... 20

Espectro 12. 1H-COSY(500 MHz, CDCl3) do composto 37b. ... 21

Espectro 13. HSQC (500 MHz, CDCl3) do composto 37b. ... 22

Espectro 14. HMBC (500 MHz, CDCl3) do composto 37b. ... 23

Espectro 15. NOESY (500 MHz, CDCl3) do composto 37b. ... 24

Espectro 17. RMN-1H (400 MHz, CDCl3) do composto 38a. ... 26

Espectro 18. RMN-13C(100 MHz, CDCl3) do composto 38a. ... 27

Espectro 21. HMBC (400 MHz, CDCl3) do composto 38a. ... 30

Espectro 23. EM-IES do composto 38b. ... 32

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Espectro 31. RMN-13C (100 MHz, CDCl3) do composto 39a. ... 40

Espectro 44. EM-IE do composto 40a. ... 53

Espectro 48. 1H-COSY (400 MHz, CDCl3) do composto 40b. ... 57

Espectro 52. RMN-1H (400 MHz, CDCl3) do composto 40c. ... 61

Espectro 53. RMN-13C (100 MHz, CDCl3) do composto 40c. ... 62

Espectro 54. 1H-COSY (400 MHz, CDCl3) do composto 40c... 63

Espectro 55. HSQC (400 MHz, CDCl3) do composto 40c. ... 64

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Espectro 57. NOESY (400 MHz, CDCl3) do composto 40c. ... 66

Espectro 70. EM-IE do composto 42a. ... 79

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Espectro 157. EM-IES do composto 51. ... 166

Espectro 158. RMN-1H (400 MHz, CDCl3) do composto 51. ... 167

Espectro 159. RMN-13C (100 MHz, CDCl3) do composto 51. ... 168

Espectro 160. 1H-COSY (400 MHz, CDCl3) do composto 51. ... 169

Espectro 161. HSQC (400 MHz, CDCl3) do composto 51. ... 170

Espectro 162. HMBC (400 MHz, CDCl3) do composto 51. ... 171

Espectro 163. NOESY (400 MHz, CDCl3) do composto 51. ... 172

Espectro 169. HMBC (500 MHz, CDCl3) do composto 52. ... 178

Espectro 173. RMN-13C (100 MHz, CDCl3) do composto 53 – ampliação de 118 à 170 ppm. ... 182

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10 13 12 11 10 9 8 7 6 5 4 3 2 1 Chemical Shift (ppm) 6.10 5.11 2.04 2.01 1.00 1.47 0.61 0.32 DMSO metanol 1. 42 1. 95 1. 96 1. 97 2. 52 2. 98 3. 34 7. 40 7. 42 7. 53 7. 55 7. 57 8. 14 8. 16 8. 36 12 .6 5 13 .1 0 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 2.01 1.00 1.00 1.00 8. 36 8. 16 8.14 7. 57 7. 55 7. 53 7. 44 7.42 7. 40 O NH N C H3 CH3 1 3.0 2.5 2.0 1.5 1.0 0.5 Chemical Shift (ppm) 6.10 5.11 2.04 1.47 2.04 metanol DMSO 3. 34 2. 98 2. 52 1. 97 1.96 _1.95 1. 42

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11 8 7 17 14 16 15 13 5 9 6 ₄ 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 CH₃ 22 (37a) M: 294.3909 Da [M + H]+ = 295.1805Da; err [ppm] = -1,5

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12 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 Chemical Shift (ppm) 6.23 3.17 2.22 2.03 2.03 1.02 1.02 1.01 0.98 Clorofórmio 1. 01 1. 02 1. 04 1. 48 1. 91 1. 92 1. 94 1. 99 2. 00 2. 02 3. 19 3. 21 3. 22 4. 34 4. 36 4. 37 7. 29 7. 47 7. 60 7. 80 8. 28 8. 30 8. 54 8. 55 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.02 1.02 1.01 0.98 1.00 0.53 Clorofórmio 7. 29 7. 47 7. 60 7. 80 8. 28 8. 30 8. 54 8. 55 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.23 3.17 2.22 2.03 0.68 AcOEt 3. 22 3.21 _3.19 2. 02 2.00 1. 99 _1.94 1. 92 1. 91 1. 48 1. 28 1.04 1. 02 1. 01

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13 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 Chemical Shift (ppm) Clorofórmio 11 .2 1 19 .59 25 .82 26 .5 4 32 .36 48 .60 73 .61 76 .79 77 .04 77 .29 10 1.5 8 12 1. 28 12 2. 40 12 3.5 7 12 3. 94 12 6. 45 12 8.8 0 13 3.4 0 14 0. 50 14 5.9 1

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14 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 3.18, 1.99 1.9, 0.99 7.59, 8.55 7.46, 8.29 0.99, 1.92 1.88, 4.37 4.33, 1.92 8.53, 7.58 1.97, 3.2 7.61, 7.46 8.27, 7.45 7.43, 7.59

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15 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 48.51, 4.35 19.59, 3.2 32.17, 1.99 121.14, 8.55 11.04, 1.01 25.81, 1.91 123.87, 7.47 122.17, 8.29 126.24, 7.6 140.62, 7.8 25.81, 1.48

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16 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 31.81, 1.48 73.3, 1.47 25.88, 1.48 48.07, 1.01 145.93, 3.21 25.12, 1.01 31.7, 3.2 140.33, 4.36 73.87, 2 100.9, 3.2 26.47, 1.99 73.43, 3.2 25.65, 4.35 48.25, 1.93 126.09, 8.29 128.5, 4.35 10.49, 4.35 100.9, 1.99 140.16, 8 123.29, 7.47 128.74, 7.79 126.26, 7.6 121.96, 7.6 18.44, 2 128.17, 3.21 145.87, 8.29

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17 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 3.2, 4.35 1.46, 1.99 4.35, 3.2 4.36, 1.91 1.96, 4.35

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18 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 C H₃ 22 (37b) M: 294.3909 Da [M + H]+ = 295.1805Da; err [ppm] = -1,3

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19 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 Chemical Shift (ppm) 6.34 4.42 3.12 2.10 2.10 1.03 1.02 1.00 0.98 AcOEt Clorofórmio 1. 03 1. 04 1. 06 1. 28 1. 48 2. 00 2. 02 2. 03 2. 05 2. 06 2. 08 3. 20 3. 21 3. 23 4. 51 4. 52 4. 53 7. 29 7. 50 7. 58 7. 86 8. 10 8. 12 8. 43 8. 44 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.03 1.02 1.00 0.98 Clorofórmio 8. 44 8. 43 _8.12 _8.10 7. 86 7. 58 7. 56 _7.51 7.50 7.29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.34 4.42 3.12 2.07 0.66 AcOEt 3. 23 3.21 3. 20 2. 08 2.06 2.05 2.03 2. 02 2. 00 1. 48 1. 28 1. 06 1. 04 1. 03 Espectro 10. RMN-1H (500 MHz, CDCl3) do composto 37b.

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20 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 8 Chemical Shift (ppm) 11 .0 9 18 .42 23 .43 26 .7 6 32 .41 49 .45 74 .47 77 .05 10 8.1 5 11 9. 82 12 0.9 5 12 1.2 8 12 3. 37 12 3. 49 12 4.3 8 12 5. 76 14 1.5 2 14 1. 90 14 4.7 1 Espectro 11. RMN-13C (125 MHz, CDCl3) do composto 37b.

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21 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.18, 2 7.57, 8.1 2, 1.01 2.03, 4.52 1.98, 3.21 1.01, 2.05 7.47, 8.44 8.11, 7.56 4.48, 2.04 8.44, 7.49

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22 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.63, 1.48 49.45, 4.51 18.31, 3.21 32.43, 2.01 119.82, 8.11 23.41, 2.05 10.91, 1.03 125.73, 7.58 123.13, 8.44 123.24, 7.49 141.65, 7.85 Espectro 13. HSQC (500 MHz, CDCl3) do composto 37b.

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23 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 32.01, 1.47 26.04, 1.47 49.1, 1.03 144.76, 3.21 74.15, 2.01 32.57, 3.21 141.59, 4.51 107.74, 3.21 73.91, 3.21 22.95, 1.03 23.3, 4.52 26.19, 2 10.53, 4.52 49.27, 2.05 10.64, 2.05 120.53, 4.52 107.98, 1.99 141.13, 3.21 18, 2 120.64, 7.85 122.18, 8.11 125.26, 8.44 123.55, 7.5 144.52, 8.43 120.46, 8.44 141.26, 7.86 118.73, 7.49 Espectro 14. HMBC (500 MHz, CDCl3) do composto 37b.

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24 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 4.51, 8.11 4.51, 7.86 8.11, 4.51 7.86, 4.51 8.1, 2.04

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25 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 22 CH₃ 23 (38a) M: 308.4174 Da [M + H]+ = 309.1961Da; err [ppm] = 0,5

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26 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 Chemical Shift (ppm) 5.94 3.20 2.17 2.09 2.06 1.04 1.01 1.00 1.00 clorofórmio 0. 98 1. 00 1. 01 1. 43 1. 44 1. 46 1. 48 1. 86 1. 88 1. 98 2. 00 2. 01 3. 18 3. 19 3. 21 4. 39 4. 40 4. 42 7. 29 7. 48 7. 61 7. 63 7. 92 8. 28 8. 30 8. 57 8. 59 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.04 1.03 1.01 1.00 1.00 0.70 clorofórmio 8. 59 _8.57 _8.30 _8.28 7.92 7. 63 7.61 _7.59 _7.50 7.48 _7.46 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 5.94 3.20 2.17 2.09 AcOEt 3. 21 3.19 _3.18 _2.01 2.00 _1.98 1. 90 _1.88 _1.86 1. 84 1. 48 1. 46 _1.44 _1.43 1. 41 1. 01 1. 00 0. 98

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27 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 13 .7 0 19 .56 19 .93 26 .5 3 32 .29 34 .47 47 .00 73 .71 10 1.4 9 12 1. 44 12 2. 45 12 3.7 0 12 4. 22 12 5.9 2 12 6. 65 12 8.6 8 13 2.3 4 14 0. 03 14 6.1 9

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28 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.2, 2 7.61, 8.58 7.48, 8.29 4.39, 1.86 8.57, 7.61 1.38, 0.97 8.28, 7.48 7.6, 7.48 0.97, 1.41 1.41, 1.86 7.48, 7.62 1.95, 3.18 1.85, 4.4 1.83, 1.41

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29 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.28, 1.47 19.51, 3.18 32.37, 1.99 47.04, 4.4 121.36, 8.57 122.33, 8.28 126.61, 7.61 34.18, 1.87 13.45, 0.99 124.08, 7.47 19.61, 1.42 139.9, 7.91

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30 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.09, 1.48 31.9, 1.48 25.69, 1.48 101.07, 2 32.2, 3.19 131.99, 7.93 128.63, 3.19 26.08, 2 101.25, 3.19 128.19, 7.92 19.09, 0.98 34.42, 4.4 139.83, 4.41 19.5, 4.4 145.82, 3.18 18.7, 2 72.91, 3.19 123.52, 7.48 126.8, 8.29 128.32, 4.4 125.54, 7.61 123.65, 8.58 46.66, 1.88 122.03, 7.61 72.7, 1.99 146.28, 8.28 33.07, 0.99 12.1, 1.87

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31 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.17, 4.4 4.4, 3.19 4.39, 1.86 1.85, 4.4 7.92, 4.4 3.17, 1.86

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32 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 C H₃ 23 (38b) M: 308.4174 Da [M + H]+ = 309.1961Da; err [ppm] = 0,6

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33 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 Chemical Shift (ppm) 8.45 4.14 3.21 2.04 2.02 1.07 1.00 1.00 clorofórmio 0. 98 1. 00 1. 02 1. 44 1. 46 1. 48 1. 49 1. 99 2. 00 2. 01 2. 03 3. 21 3. 22 3. 24 4. 57 4. 59 4. 60 7. 29 7. 51 7. 53 7. 59 7. 61 8. 02 8. 12 8. 14 8. 43 8. 45 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.07 1.00 1.00 1.00 0.67 clorofórmio 8. 45 _8.43 _8.14 _8.12 8. 02 7. 61 7.59 _7.57 7.53 7.51 _7.50 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 8.45 4.14 3.21 2.02 AcOEt 3. 24 3.22 _3.21 _2.03 2. 01 2. 00 1. 99 1. 53 _1.49 1. 48 1. 46 1. 44 1. 28 1. 02 1. 00 0. 98 Espectro 24. RMN-1H (400 MHz, CDCl3) do composto 38b.

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34 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 13 .6 4 18 .50 19 .82 26 .7 4 32 .07 32 .33 47 .86 74 .66 10 7.6 3 11 9. 87 12 0.7 5 12 1.1 9 12 3. 45 12 4.5 2 12 5. 97 14 0.3 6 14 1. 28 14 5.1 4 Espectro 25. RMN-13C (100 MHz, CDCl3) do composto 38b.

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35 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 1.51, 0.98 1.94, 4.59 1.94, 3.21 7.58, 8.12 7.56, 8.44 3.18, 2.01 4.54, 1.99 8.42, 7.52 1.01, 1.4 8.08, 7.58 1.43, 2 2, 1.4

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36 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 107.46, 3.22 25.84, 1.47 18.94, 2.01 74.8, 2.01 74.48, 3.22 140.87, 4.59 144.63, 3.22 31.75, 3.22 120.51, 4.59 107.02, 2 120.61, 8.02 31.09, 0.99 19.26, 0.98 125.85, 8.44 124.61, 7.51 31.42, 4.59 77.04, 7.54 141.24, 7.76 139.81, 3.22 119.66, 7.5 13.01, 1.45 32.07, 1.46 47.21, 1.47 47.21, 2 18.61, 4.58 140.16, 8.03 144.82, 8.44 25.17, 2 Espectro 27. HMBC (400 MHz, CDCl3) do composto 38b.

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37 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 1.98, 3.22 8.1, 4.58 4.55, 8.13 1.45, 3.21 1.97, 4.58 8.12, 2

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38 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 22 23 CH₃ 24 (39a) M: 322.444 Da [M + H]+ = 323.2118Da; err [ppm] = -0,8

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39 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 Chemical Shift (ppm) 5.80 3.17 2.11 1.89 1.85 1.03 1.00 0.93 clorofórmio 0. 91 0. 93 0. 95 1. 27 1. 39 1. 40 1. 40 1. 48 1. 57 1. 93 1. 98 2. 00 2. 15 3. 16 3. 17 3. 19 4. 48 4. 50 4. 52 7. 29 7. 52 7. 65 7. 67 8. 28 8. 30 8. 43 8. 65 8. 67 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.03 1.01 1.00 0.93 0.93 clorofórmio 8. 67 _8.65 _8.43 _8.30 _8.28 7. 67 7.65 _7.63 _7.54 7.52 7. 50 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 5.80 3.17 2.11 1.89 0.76 acetona AcOEt 3. 19 3.17 _3.16 2. 15 2. 01 2.00 _1.98 1. 95 _1.93 _1.91 _1.57 1. 48 1. 40 1. 40 1. 39 1. 27 _0.95 0. 93 0. 91 4.29

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40 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 13 .9 2 19 .42 22 .28 26 .5 0 28 .72 31 .96 32 .10 47 .94 74 .06 10 1.1 7 12 1. 95 12 2. 57 12 4.1 3 12 4.2 6 12 5. 11 12 7. 29 12 8.2 9 12 8.9 7 13 8. 97 14 7.1 3 145 140 135 130 125 120 Chemical Shift (ppm) 14 7.1 3 13 8. 97 12 8.9 7 12_8.2 9 12 7. 29 12 5. 11 12 4.2 6 12_4.1 3 12 2. 57 12 1. 95

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41 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.16, 1.98 1.91, 4.51 7.51, 8.28 1.36, 0.91 7.64, 7.51 1.9, 1.38 8.28, 7.51 7.63, 8.64 4.49, 1.92 8.64, 7.65 0.89, 1.38 7.51, 7.66 1.37, 1.91 1.95, 3.16

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42 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 121.94, 8.65 122.4, 8.27 32.19, 1.98 124.89, 7.51 127.11, 7.63 26.55, 1.48 13.86, 0.9 28.56, 1.4 47.51, 4.5 138.77, 8.44 22.31, 1.4 18.89, 3.17

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43 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.59, 1.48 31.33, 1.48 25.49, 1.48 26.14, 1.99 147.02, 3.17 100.86, 1.99 77.19, 7.54 126.87, 8.29 73.26, 2 127.78, 3.17 75.52, 1.57 138.44, 4.5 100.14, 3.17 124.02, 8.66 123.35, 7.65 124.15, 7.52 25.49, 1.63 121.44, 7.52 127.61, 4.5 25.49, 1.31 30.96, 4.5 27.75, 4.5 147.26, 8.29 20.96, 0.92 73.13, 3.16 129.06, 8.66 30.42, 3.17

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44 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 4.49, 3.16 3.14, 4.49 1.38, 1.93 8.44, 4.5 4.5, 1.9 1.35, 4.49 1.87, 4.49

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45 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 C H₃ 24 (39b) M: 322.444 Da [M + H]+ = 323.2118Da; err [ppm] = -2,1

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46 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 Chemical Shift (ppm) 12.36 4.50 3.80 3.60 2.16 1.64 1.35 1.12 1.06 clorofórmio 0. 91 0. 93 0. 95 1. 27 1. 40 1. 42 1. 43 1. 48 2. 00 2. 01 2. 13 3. 23 3. 25 3. 27 4. 66 4. 68 4. 70 7. 29 7. 57 7. 58 7. 62 7. 64 7. 66 8. 12 8. 14 8. 44 8. 47 8. 58 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.64 1.35 1.12 1.12 1.06 1.00 clorofórmio 8. 58 8.47 8.44 8.14 8.12 7. 66 7.64 _7.62 _7.58 7.57 7. 55 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 12.36 4.50 3.80 3.60 AcOEt 3. 27 3.25 _3.23 2.13 _2.06 _2.03 2.01 2. 00 1. 48 1. 44 _1.43 _1.42 _1.42 1. 27 0.95 0. 93 0. 91 Espectro 37. RMN-1H (400 MHz, CDCl3) do composto 39b.

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47 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 Chemical Shift (ppm) 13 .9 2 18 .68 22 .23 26 .7 1 28 .61 29 .57 32 .04 48 .86 75 .23 77 .2 4 10 5.9 9 11 9. 92 12 0.1 0 12 0.9 5 12 3. 70 12 4. 58 12 4.9 3 12 6. 69 13 6.8 5 13 9. 80 14 6.4 4 145 140 135 130 125 120 Chemical Shift (ppm) 14 6.4 4 13 9. 80 13 6.8 5 12 6. 69 12 4.9 3 12 4. 58 12 3. 70 12 0.9 5 12 0.1 0 11 9. 92 Espectro 38. RMN-13C (100 MHz, CDCl3) do composto 39b.

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48 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.25, 2 7.55, 8.46 2.06, 1.42 7.64, 8.13 4.67, 2.04 1.4, 0.92 8.14, 7.64 8.44, 7.56 0.9, 1.39 1.96, 3.24 2.03, 4.68 1.42, 2.05

(49)

49 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.46, 1.46 48.82, 4.66 123.74, 8.44 18.41, 3.22 119.77, 8.11 126.64, 7.62 28.64, 1.42 13.74, 0.89 32.32, 2 21.99, 1.4 29.84, 2.04 124, 7.56 139.85, 8.58

(50)

50 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.98, 1.47 31.57, 1.47 25.99, 1.47 124.46, 8.13 21.54, 0.93 105.87, 2.01 74.98, 2.01 25.99, 2.01 105.76, 3.24 126.59, 8.46 119.81, 4.68 146.28, 3.24 139.33, 4.68 31.68, 3.24 28.34, 4.68 120.68, 8.46 75.02, 3.24 122, 7.63 119.55, 7.56 124.46, 7.56 146.37, 8.46 136.59, 3.24

(51)

51 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 8.13, 4.68 4.69, 8.13 2.05, 8.13 8.59, 4.68

(52)

52 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 CH₃ 25 M: 336.4706 Da (40a) [M + H]+ = 337,2283 Da; err [ppm] = -2,5

(53)

53 400 350 300 250 200 150 100 50 m/z 43 115 ₁₄₀ 168 223 251 280 336 355 405 N N O C H₃ CH₃ CH3 m/z: 336 +. CH2 C H3 C H3 N N CH₂ O CH3 m/z: 280 +. N N O C H3 CH3 C H2 CH3 m/z: 251

(54)

54 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 C H₃ 25 (40b) M: 336.4706 Da [M + H]+ = 337,2274 Da; err [ppm] = -2,5

(55)

55 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 Chemical Shift (ppm) 9.00 4.22 4.02 2.17 1.99 1.08 1.07 1.00 8. 45 _8.43 8. 13 _8.11 7.98 7. 61 7. 59 7. 53 7.51 7. 29 4. 59 4. 57 4. 55 3. 22 2. 01 2. 00 1. 48 1. 34 1. 28 0. 90 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.08 1.07 1.00 0.99 1.00 clorofórmio 8. 45 _8.43 8. 13 _8.11 _7.98 7. 61 7.59 _7.57 7.53 7.51 _7.49 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 9.00 6.02 4.22 4.02 2.17 3. 22 2. 01 2. 00 1. 48 1. 44 1. 34 1. 28 0. 90 Espectro 46. RMN-1H (400 MHz, CDCl3) do composto 40b.

(56)

56 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 Chemical Shift (ppm) 13 .9 8 18 .49 22 .51 26 .29 26 .7 4 29 .72 30 .04 32 .32 48 .15 74 .66 10 7.6 0 11 9. 86 12 0.7 5 12 1.1 8 12 3. 46 12 3. 77 12 4.5 2 12 5. 98 14 0.3 3 14 1. 22 14 5.1 5 145 140 135 130 125 120 Chemical Shift (ppm) 14 5.1 5 14 1. 22 14 0.3 3 12 5. 98 12 4.5 2 12 3. 77 12 3. 46 12 1.1 8 12 0.7 5 11 9. 86 Espectro 47. RMN-13C (100 MHz, CDCl3) do composto 40b.

(57)

57 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 7.51, 8.44 1.98, 3.2 1.32, 0.89 0.89, 1.34 7.56, 8.12 4.54, 1.99 8.13, 7.59 1.99, 4.57 8.45, 7.51 3.18, 2 2, 1.42 7.61, 7.51 1.39, 2 7.47, 7.59

(58)

58 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.37, 1.47 48.07, 4.56 32.32, 2 18.39, 3.22 123.4, 8.44 119.74, 8.11 29.87, 2 13.73, 0.9 125.91, 7.59 123.61, 7.52 22.23, 1.31 141.18, 7.99 29.24, 1.26 Espectro 49. HSQC (400 MHz, CDCl3) do composto 40b.

(59)

59 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.32, 1.47 32.16, 1.48 26.51, 1.48 21.87, 0.89 31.27, 0.9 107.48, 2 26.73, 2.01 107.41, 3.21 74.45, 2.01 141.11, 4.57 26.21, 4.57 32.2, 3.21 144.85, 3.22 29.73, 4.57 124.22, 7.51 126.09, 8.44 123.02, 8.12 74.61, 3.21 120.2, 4.57 119.64, 7.51 125.02, 8.12 48.23, 2.01 144.89, 8.44 139.83, 8 139.7, 3.21 Espectro 50. HMBC (400 MHz, CDCl3) do composto 40b.

(60)

60 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 8.12, 4.57 4.56, 8.12 1.99, 3.21 2, 4.57 1.99, 8.12

(61)

61 10 9 8 7 6 5 4 3 2 1 Chemical Shift (ppm) 25.09 10.06 8.23 4.19 2.66 1.03 1.02 1.01 1.00 0.54 clorofórmio 0. 91 1. 27 1. 37 1. 53 1. 89 2. 06 2. 15 3. 26 4. 43 4. 83 4. 96 7. 29 7. 47 7. 59 7. 70 7. 71 7. 78 7. 95 8. 17 8. 18 8. 27 8. 49 8. 51 8. 55 10 .6 4 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.03 0.32 1.02 0.30 1.01 0.990.32 0.30 8. 55 8. 51 _8.49 8. 29 _8.27 8. 18 _8.17 7. 95 7. 78 7. 77 _7.71 7.70 7. 59 7. 47 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 25.09 10.06 8.23 2.66 3. 26 2. 15 2. 06 1. 89 1. 53 1. 49 1. 37 1. 27 0. 91 8 7 17 14 16 15 10 5 9 6 4 3 2 O 1 N 11 12 N+ 13 C H3 18 CH193 26 27 28 29 30 C H₃ 31 20 21 22 23 24 CH3 25 I -32 Espectro 52. RMN-1H (400 MHz, CDCl3) do composto 40c.

(62)

62 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) clorofórmio 13 .98 19 .3 7 22 .4 6 22 .4 8 26 .0 4 26 .44 29 .3 8 31 .2 1 31 .6 7 31 .9 4 47 .3 5 49 .8 1 50 .6 0 75 .3 0 10 1. 34 12 0.2 0 12 0. 62 12 2.4 5 12 4.2 6 12 5. 72 12 6.7 5 12 8.7 3 12 9. 56 13 9.8 7 14 9. 62 155 150 145 140 135 130 125 120 Chemical Shift (ppm) 14 9. 62 13 9.8 7 12 9. 56 12 8.7 3 12 6.7 5 12 6.6 5 12 5. 72 12 4.2 6 12 2.4 5 12 1.4 4 12 0. 62 12 0. 53 12 0.2 0 Espectro 53. RMN-13C (100 MHz, CDCl3) do composto 40c.

(63)

63 11 10 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 pp m 1.35, 0.89 2.04, 3.23 7.7, 8.5 0.89, 1.36 3.27, 2.03 7.76, 8.17 2.06, 4.8 8.53, 7.71 2.13, 1.57 1.55, 2.13 2.1, 4.95 8.18, 7.78 4.98, 2.13 3.17, 1.98 7.45, 8.27 4.81, 2.04 1.48, 2.04 1.98, 3.17 1.86, 4.41 4.39, 1.87 8.56, 7.57 8.29, 7.46 1.38, 1.87

(64)

64 11 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 13.91, 0.88 31.23, 1.34 31.83, 2.01 22.31, 1.33 49.66, 4.79 120.1, 8.15 50.6, 4.95 124.1, 8.48 19.01, 3.23 128.78, 7.76 29.63, 2.11 126.67, 7.68 47.17, 4.39 25.82, 1.36 122.37, 8.26 12.82, 0.9 Espectro 55. HSQC (400 MHz, CDCl3) do composto 40c.

(65)

65 11 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.74, 1.52 22.17, 0.9 30.9, 1.52 _{31.16, 0.89} 100.94, 3.24 26.38, 2.05 101.7, 2.05 128.52, 8.5 74.74, 2.05 149.12, 3.25 25.28, 1.51 31.16, 3.25 120.33, 8.5 125.28, 7.69 74.74, 3.26 125.78, 8.17 119.81, 7.69 30.33, 1.35 128.8, 3.25 Espectro 56. HMBC (400 MHz, CDCl3) do composto 40c.

(66)

66 11 10 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 11.5 pp m 2.02, 3.24 3.22, 2.04 4.94, 8.17 8.19, 4.95 3.22, 4.81 2.1, 8.17 4.79, 3.22 4.94, 2.12 4.81, 2.04

(67)

67 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 22 23 24 25 CH₃ 26 (41a) M: 350.4972 Da [M+H]+: 351.2431 Da; err [ppm] = 0,4

(68)

68 9 8 7 6 5 4 3 2 1 Chemical Shift ( ppm) 22.99 7.98 2.41 2.00 1.98 1.56 1.00 1.07 1.13 0.58 0. 88 0. 90 1. 27 1. 32 1. 49 1. 53 1. 91 2. 00 2. 01 2. 07 2. 08 2. 16 3. 20 3. 21 3. 28 3. 67 4. 41 4. 43 4. 44 4. 81 4. 93 7. 28 7. 46 7. 48 7. 58 7. 71 7. 79 8. 01 8. 18 8. 28 8. 30 8. 50 8. 52 9. 76 9.5 9.0 8.5 8.0 7.5 Chemical Shift ( ppm) 1.56 1.00 1.00 0.60 1.07 0.58 clorofórmio 9. 76 8.52 8.50 8. 30 _8.28 8. 19 _8.18 8.01 7. 79 _7.71 7. 59 7.58 _7.56 7.49 7.48 7. 28 3.0 2.5 2.0 1.5 1.0 Chemical Shift ( ppm) 22.99 7.98 4.66 2.41 2.13 1.98 3. 28 3.21 3. 20 2. 16 2.08 2.07 _2.06 2. 01 2. 00 1. 92 _1.91 _1.90 1. 56 1. 53 1. 49 1. 41 1. 32 1.27 0.90 0. 88

(69)

69 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .0 5 19 .46 19 .58 22 .54 26 .5 4 26 .67 28 .84 31 .64 32 .44 47 .49 73 .82 75 .40 76 .78 77 .04 77 .29 10 1.4 0 10 1.5 1 12 0.6 0 12 1. 37 12 2. 53 12 3.8 2 12 4. 37 12 5.8 5 12 6. 73 12 8.7 2 13 1.7 1 13 9. 05 13 9. 98 14 6.4 0 14 9.8 3 145 140 135 130 125 120 Chemical Shift (ppm) 14 9.8 3 14 6.4 0 13 9. 98 13 9. 05 13 1.7 1 12_8.7 2 12 6. 73 12 5.8 5 12 5.5 8 12 4. 37 12 3.8 2 12 2. 53 12 1. 37 12 0.6 0

(70)

70 10 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 pp m 1.29, 0.91 3.18, 1.99 1.3, 0.88 7.44, 8.28 7.54, 8.51 1.97, 3.2 3.26, 2.06 0.91, 1.31 1.88, 4.42 7.77, 8.19 4.41, 1.89 7.58, 7.47 2.12, 4.93 2.02, 3.28 1.37, 1.89 8.51, 7.57 1.91, 1.38 2.05, 4.8 4.79, 2.06 2.15, 1.57 4.9, 2.15 8.29, 7.47 0.88, 1.27 1.53, 2.15 7.43, 7.58 8.17, 7.79 1.65, 2.4

(71)

71 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 pp m 33.7, 1.47 19.38, 1.48 22.78, 1.29 121.35, 8.51 38.81, 1.31 29.33, 1.31 127.43, 7.57 122.93, 8.29 47.18, 4.44 124.28, 7.47 14.77, 1.31

(72)

72 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.63, 1.48 26.17, 1.48 31.83, 1.48 75.54, 1.52 31.09, 0.89 26.04, 1.52 22.26, 0.88 101.12, 3.21 101.36, 2.01 146.43, 3.21 31.7, 3.21 73.5, 3.21 139.87, 4.43 26.17, 1.6 100.92, 3.28 101.36, 2.06 129.54, 9.77 126.09, 8.28 31.49, 3.28 73.24, 2 125.89, 8.18 149.8, 3.28 75.15, 3.28 139.03, 4.81 31.77, 4.43 74.87, 2.06 120.05, 9.76 128.45, 4.43 19.07, 2.06 26.25, 4.43 128.37, 3.21 122.79, 7.46 121.53, 7.57 129.63, 3.28 120.81, 4.93 31.62, 4.81 146.34, 8.28 120.61, 8.51 131.56, 8.51 26.25, 4.81 149.8, 8.5

(73)

73 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 25 C H₃ 26 (41b) M: 350.4972 Da [M+H]+: 351.2431 Da; err [ppm] = -3,7

(74)

74 9 8 7 6 5 4 3 2 1 Chemical Shift (ppm) 30.73 11.41 7.39 2.52 1.95 1.87 1.09 1.00 0.98 0.61 0.59 clorofórmio 0. 88 0. 89 0. 91 1. 02 1. 28 1. 30 1. 48 1. 54 2. 01 2. 08 2. 18 2. 38 3. 19 3. 21 3. 23 3. 29 3. 67 3. 76 4. 55 4. 57 4. 58 4. 81 4. 93 4. 95 4. 97 7. 29 7. 50 7. 51 7. 53 7. 59 7. 61 7. 83 7. 95 8. 12 8. 14 8. 19 8. 43 8. 45 8. 53 9. 81 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 2.52 1.09 1.00 0.98 0.97 0.37 clorofórmio 8. 53 _8.51 8. 45 _8.43 8. 21 _8.19 8. 14 _8.12 7.95 7. 78 _7.74 _7.72 _7.61 7. 59 7. 57 _7.53 _7.51 7. 50 7. 29 Espectro 65. RMN-1H (400 MHz, CDCl3) do composto 41b.

(75)

75 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .04 18 .4 5 22 .5 6 26 .47 26 .5 9 26 .74 28 .8 0 30 .1 1 32 .3 5 48 .1 1 74 .6 0 76 .7 2 77 .0 3 77 .3 5 10 1. 31 10 7. 74 11 9.8 5 12 0. 82 12 1. 22 12 3.4 4 12 3.7 0 12 4. 48 12 5.9 2 12 9. 82 14 1.4 4 14 5. 03 145 140 135 130 125 120 Chemical Shift (ppm) 14 5. 03 14 1.4 4 12 9. 82 12 5.9 2 12 4. 48 12 3.7 0 12_3.4 4 12 1. 22 12 0. 82 11 9.8 5 Espectro 66. RMN-13C (100 MHz, CDCl3) do composto 41b.

(76)

76 11 10 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.5 - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 10.5 11.0 pp m 1.31, 0.89 3.2, 2 1.99, 3.21 7.57, 8.13 7.5, 8.44 2, 4.56 4.57, 2 0.88, 1.33 2.06, 3.29 3.28, 2.07 1.41, 2.01 8.12, 7.59 2.02, 1.4 2.16, 4.95 7.7, 8.53 8.43, 7.5 4.84, 2.08 4.95, 2.17

(77)

77 11 10 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.41, 1.47 29.69, 1.26 32.3, 1.99 48.02, 4.58 22.46, 1.29 119.77, 8.11 14.07, 0.87 18.41, 3.22 123.32, 8.43 125.81, 7.57 123.39, 7.48 29.79, 2 Espectro 68. HSQC (400 MHz, CDCl3) do composto 41b.

(78)

78 11 10 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.48, 1.47 26.56, 1.48 31.96, 1.48 22.39, 0.89 31.75, 1.53 _{31.44, 0.89} 26.67, 2.01 107.5, 2 107.89, 3.21 74.76, 1.52 74.22, 2.01 74.48, 3.2 32.27, 3.2 141.24, 4.56 144.76, 3.21 121.05, 7.95 125.72, 8.44 140.5, 7.96 122.92, 8.12 29.62, 4.56 26.56, 4.56 120.92, 7.58 123.05, 7.59 120.51, 4.56 119.72, 7.51 124.26, 7.51 145.04, 8.44 Espectro 69. HMBC (400 MHz, CDCl3) do composto 41b.

(79)

79 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 m/z 41 77 115 168 198 211 251 279 308 364 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 CH₃ 27 (42a) M: 364.5238 Da

(80)

80 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 Chemical Shift (ppm) 12.78 3.41 2.22 2.18 2.00 1.09 1.08 1.08 1.03 clorofórmio 0. 87 0. 89 0. 90 1. 27 1. 30 1. 39 1. 48 1. 57 1. 92 1. 98 2. 00 2. 01 3. 16 3. 17 3. 19 4. 46 4. 48 4. 50 7. 29 7. 52 7. 65 7. 66 8. 28 8. 30 8. 35 8. 66 8. 68 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.09 1.08 1.08 1.08 1.03 clorofórmio 8. 68 _8.66 _8.35 _8.30 _8.28 7. 66 7.65 7. 63 _7.54 7.52 7. 50 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 12.78 3.41 2.22 2.00 0.39 H2O 3. 19 3. 17 3. 16 _2.01 2. 00 1. 98 1. 93 1.92 _1.90 1.57 1. 48 1. 32 1.30 1. 27 0. 90 0. 89 0. 87

(81)

81 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .04 18 .4 5 22 .5 6 26 .47 26 .5 9 26 .74 28 .8 0 30 .1 1 32 .3 5 48 .1 1 74 .6 0 76 .7 2 77 .0 3 77 .3 5 10 1. 31 10 7. 74 11 9.8 5 12 0. 82 12 1. 22 12 3.4 4 12 4. 48 12 5.9 2 12 9. 82 14 1.4 4 14 5. 03 145 140 135 130 125 120 Chemical Shift (ppm) 14 5. 03 14 1.4 4 12 9. 82 12 8.8 1 12 6.8 9 12 5.9 2 12 4. 48 12 4.3 2 12 3.7 0 12_3.4 4 12 1. 22 12 0. 82 12 0.2 4 11 9.8 5

(82)

82 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 1.98, 3.16 7.51, 8.29 1.27, 0.87 8.67, 7.64 3.16, 1.98 4.47, 1.89 7.66, 7.51 8.26, 7.51 1.9, 4.48 7.5, 7.64 1.9, 1.4 0.85, 1.28 1.4, 1.9

(83)

83 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.39, 1.47 47.49, 4.45 14, 0.87 19.17, 3.15 121.64, 8.65 122.32, 8.27 127.09, 7.62 22.33, 1.26 31.57, 1.25 29.08, 1.29 31.88, 1.99 139.48, 8.35

(84)

84 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.69, 1.47 31.92, 1.48 26.21, 1.48 22.21, 0.88 76.97, 7.55 76.97, 7.02 146.82, 3.17 100.9, 1.99 26.51, 1.99 31.88, 3.16 73.82, 3.18 73.43, 1.99 127.76, 3.17 101.27, 3.17 19.11, 1.99 126.24, 8.28 128.95, 8.34 128.3, 4.48 139.07, 4.48 124.28, 7.51 122.18, 7.51 31.79, 4.48 26.23, 4.48 146.86, 8.28 124.59, 8.66

(85)

85 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 1.98, 3.18 3.17, 4.49 1.87, 4.49 4.5, 3.16

(86)

86 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 C H₃ 27 (42b) M: 364.5238 Da [M+H]+ = 365.2587 Da; err[ppm] = -0,3

(87)

87 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 Chemical Shift (ppm) 12.54 4.14 3.39 2.00 2.00 1.07 1.05 1.00 clorofórmio 0. 87 0. 89 0. 90 1. 28 1. 30 1. 32 1. 48 2. 00 2. 01 2. 03 3. 20 3. 22 3. 24 4. 54 4. 56 4. 58 7. 29 7. 51 7. 53 7. 59 7. 61 7. 92 8. 11 8. 13 8. 43 8. 45 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.07 1.05 1.02 1.00 clorofórmio 8. 45 _8.43 _8.13 _8.11 7. 92 7. 61 7.59 _7.57 7.53 7.51 _7.49 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 12.54 4.14 3.39 2.00 3. 24 3. 22 3. 20 2.03 2. 01 2. 00 1. 48 1. 32 1.30 1. 28 0. 90 0. 89 0. 87 Espectro 78. RMN-1H (400 MHz, CDCl3) do composto 42b.

(88)

88 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 Chemical Shift (ppm) 14 .0 9 18 .46 22 .61 26 .62 26 .7 5 29 .09 30 .10 32 .36 48 .05 74 .59 10 7.8 5 11 9. 86 12 0.8 3 12 1.2 2 12 3. 42 12 3. 66 12 4.4 6 12 5. 88 14 0.8 2 14 1. 44 14 4.9 7 145 140 135 130 125 120 Chemical Shift (ppm) 14 4.9 7 14 1. 44 14 0.8 2 12 5. 88 12 4.4 6 12 3. 66 12 3. 42 12 1.2 2 12 0.8 3 11 9. 86 Espectro 79. RMN-13C (100 MHz, CDCl3) do composto 42b.

(89)

89 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 2, 3.21 3.21, 2 7.59, 8.12 7.5, 8.44 4.55, 2 8.11, 7.58 7.59, 7.51 0.85, 1.27 8.45, 7.5 1.99, 4.55 1.39, 2 1.98, 1.4 1.25, 0.88 7.47, 7.59

(90)

90 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 47.93, 4.55 18.07, 3.2 119.73, 8.11 123.3, 8.43 123.51, 7.49 125.83, 7.57 26.67, 1.47 32.03, 1.26 141.57, 7.92 13.92, 0.89 30.2, 1.28 29.81, 2.01 22.52, 1.29

(91)

91 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.06, 1.47 32.2, 1.47 26.21, 1.48 107.39, 3.21 22.24, 0.88 31.68, 0.88 107.46, 2.01 77.21, 7.02 32.22, 3.22 76.91, 7.55 18.2, 2.01 120.77, 7.92 74.06, 2.01 141.31, 4.56 120.96, 4.56 74.06, 3.22 26.54, 2 29.86, 4.56 125.65, 8.44 140.26, 3.22 26.19, 4.56 123.2, 8.12 143.91, 3.21 124.7, 7.51 125.24, 8.12 119.4, 7.51 48.07, 2.01 144.95, 8.44 140.46, 7.92

(92)

92 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 8.12, 4.56 4.56, 7.92 4.55, 8.12 1.99, 8.12 7.92, 4.56

(93)

93 8 7 17 14 16 15 13 5 9 6 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 27 CH₃ 28 M: 378.5503 Da (43a) [M+H]+ = 379.2744 Da; err[ppm] = -1,9

(94)

94 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 27 C H₃ 28 (43b) M: 378.5503 Da [M+H]+ = 379.2744 Da; err[ppm] = 2,2

(95)

95 9 8 7 6 5 4 3 2 1 Chemical Shift ( ppm) 17.03 4.18 4.04 2.09 2.06 1.07 1.04 1.02 0.07 clorofórmio 8. 44 _8.43 _8.12 _8.11 7. 88 7. 58 _7.50 7. 28 4. 56 4. 54 4. 53 3. 22 3. 21 3. 19 2. 02 2. 01 1. 99 1. 53 1. 48 1. 43 1. 27 0. 90 0. 89 0. 87 8.5 8.0 7.5 7.0 Chemical Shift ( ppm) 1.07 1.04 1.02 1.00 0.47 clorofórmio 8. 44 _8.43 _8.12 _8.11 7. 88 7. 58 _7.50 7. 28 3.0 2.5 2.0 1.5 1.0 Chemical Shift ( ppm) 17.03 4.18 4.04 2.06 0.56 3. 22 3. 21 3. 19 2. 02 2. 01 1. 99 1. 53 1. 48 1. 43 1. 31 1. 27 0. 90 0. 89 0. 87 Espectro 86. RMN-1H (500 MHz, CDCl3) do composto 43b.

(96)

96 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .0 7 18 .4 6 22 .61 22 .6 2 26 .61 26 .7 6 29 .15 29 .39 30 .1 6 31 .78 32 .4 3 47 .95 74 .49 76 .77 77 .02 77 .28 10 8.0 1 11 9. 83 12 0. 23 12 0.9 4 12 1.2 8 12 3. 40 12 4.4 5 12 5. 77 12 6. 85 12 8. 76 14 1.2 2 14 1. 64 14 4.8 3 30 25 20 15 Chemical Shift (ppm) 32 .4 3 31 .78 30 .1 6 29 .39 29.15 29 .11 26 .7 6 26 .61 22 .6 2 22 .61 18 .4 6 14 .0 7 Espectro 87. RMN-13C (125 MHz, CDCl3) do composto 43b.

(97)

97 10 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 pp m 3.18, 1.99 1.99, 3.2 7.57, 8.11 7.51, 8.43 1.28, 0.88 1.97, 4.54 4.53, 1.99 7.59, 7.49 1.99, 1.4 8.12, 7.57 0.88, 1.27 1.38, 1.99 7.44, 7.57 8.41, 7.49

(98)

98 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 pp m 142.3, 7.87 125.78, 7.57 123.85, 7.49 119.72, 8.11 37.05, 2.01 24.25, 2.01 48.23, 4.54 21.96, 3.2 13.99, 3.2 Espectro 89. HSQC (500 MHz, CDCl3) do composto 43b.

(99)

99 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 74.48, 1.47 26.6, 1.47 32.05, 1.47 107.78, 3.2 26.43, 2 22.41, 0.87 107.87, 2 32.22, 3.2 141.55, 4.54 144.89, 3.2 74.04, 3.2 120.83, 7.88 74.45, 1.99 26.32, 4.54 30.29, 4.54 124.41, 7.49 124.54, 8.12 125.65, 8.43 141.09, 7.88 119.59, 7.5 120.96, 8.44 120.46, 4.54 141.07, 3.2 47.86, 2 144.65, 8.43 Espectro 90. HMBC (500 MHz, CDCl3) do composto 43b.

(100)

100 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 27 28 29 30 CH₃ 31 (44a) M: 420.6301 Da [M+H]+ = 421.3213 Da; err[ppm] = -0,9

(101)

101 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 Chemical Shift (ppm) 21.51 3.43 2.14 2.02 1.99 1.02 1.00 1.00 0.98 clorofórmio 8. 57 _8.55 8. 30 _8.28 7. 84 7. 62 7. 60 _7.47 7. 28 4. 40 4. 38 4. 36 3. 22 3. 20 3. 18 _2.02 2. 00 1. 98 1. 88 1. 87 1. 48 1. 36 1. 27 0. 91 0. 90 0. 88 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.02 1.01 1.00 1.00 0.98 clorofórmio 7. 28 7. 46 7. 47 7. 49 7. 59 7. 60 7. 62 7. 84 8. 28 8. 30 8. 55 8. 57 3.0 2.5 2.0 1.5 1.0 0.5 Chemical Shift (ppm) 21.51 3.43 2.14 2.02 3. 22 3. 20 3. 18 _2.02 2. 00 1. 98 1. 90 1.88 _1.87 1. 85 1. 48 1. 36 1. 27 0. 91 0. 90 0. 88

(102)

102 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .1 4 19 .59 22 .70 26 .5 3 26 .72 29 .34 29 .61 32 .33 32 .50 47 .15 73 .65 76 .72 77 .05 77 .36 10 1.5 3 12 1. 36 12 2. 42 12 3.6 3 12 4. 07 12 6.1 9 12 6. 54 12 8.7 4 13 2.9 0 14 0. 21 14 6.0 3 33.0 32.5 32.0 31.5 31.0 30.5 30.0 29.5 29.0 Chemical Shift (ppm) 32 .50 32.33 31.90 29.61 .6029 29.53 29.46 29.34 29.18

(103)

103 10 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.17, 1.98 7.45, 8.29 7.59, 8.56 4.36, 1.86 1.3, 0.89 1.97, 3.19 8.56, 7.6 7.61, 7.47 1.35, 1.86 8.29, 7.47 1.88, 1.38 7.45, 7.61 0.88, 1.31 1.86, 4.38

(104)

104 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 29.52, 1.27 26.29, 1.48 13.94, 0.89 19.46, 3.19 47.12, 4.38 26.62, 1.25 140.44, 7.83 32.19, 2 124.02, 7.48 126.35, 7.61 122.43, 8.29 22.42, 1.3 121.04, 8.56 32.09, 1.26

(105)

105 10 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.39, 1.48 32.22, 1.48 25.93, 1.48 26.12, 2 21.93, 0.89 145.8, 3.19 32.18, 3.19 101.25, 2 73.28, 3.2 128.3, 7.84 73.65, 1.99 31.27, 0.89 19.26, 2 77.1, 7.54 123.65, 8.56 101.51, 3.2 139.92, 4.38 77.1, 7.02 126.46, 8.29 128.45, 4.38 128.8, 3.19 26.58, 4.38 32.44, 4.38 125.87, 7.6 123.65, 7.46 122.4, 7.61 46.9, 7.84 132.93, 7.83 26.32, 1.89 132.71, 8.56 145.91, 8.29

(106)

106 10 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 1.48, 1.98 3.18, 4.37 4.36, 7.83 1.3, 1.88 1.92, 3.18 1.87, 4.37 4.38, 1.86 7.84, 4.37 1.44, 3.18 1.32, 4.37 3.16, 1.86

(107)

107 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 23 24 25 26 27 28 29 30 C H₃ 31 (44b) M: 420.6301 Da [M+H]+ = 421.3213 Da; err[ppm] = 2,3

(108)

108 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 Chemical Shift (ppm) 21.84 4.57 3.84 2.15 2.12 1.09 1.06 1.05 1.03 clorofórmio 0. 88 0. 90 0. 91 1. 27 1. 36 1. 48 1. 99 2. 01 2. 03 3. 20 3. 21 3. 23 4. 52 4. 54 4. 56 7. 28 7. 50 7. 52 7. 57 7. 86 8. 11 8. 13 8. 42 8. 45 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.09 1.06 1.05 1.03 clorofórmio 8. 45 _8.42 8. 13 _8.11 7. 86 7. 59 7.57 7.56 7.52 7. 50 7. 48 7. 28 3.0 2.5 2.0 1.5 1.0 0.5 Chemical Shift (ppm) 21.84 6.49 4.57 3.84 2.12 3. 23 3. 21 3. 20 2. 03 2. 01 1. 99 1. 48 1. 43 _1.36 1. 27 0. 91 0. 90 0. 88 Espectro 99. RMN-1H (400 MHz, CDCl3) do composto 44b.

(109)

109 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .1 4 18 .43 26 .63 26 .7 5 29 .14 29 .46 29 .60 32 .39 47 .94 74 .50 76 .72 77 .05 77 .36 10 8.0 5 11 9. 84 12 0.9 2 12 1.2 5 12 3. 38 12 3. 54 12 4.4 0 12 5. 78 14 1.2 6 14 1. 68 14 4.7 8 145 140 135 130 125 120 Chemical Shift (ppm) 14 4.7 8 14 1. 68 14 1.2 6 12 5. 78 12 4.4 0 12 3. 54 12 3. 38 12 1.2 5 12 0.9 2 11 9. 84 Espectro 100. RMN-13C (100 MHz, CDCl3) do composto 44b.

(110)

110 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.19, 2 7.57, 8.11 7.5, 8.43 1.98, 3.2 1.39, 1.99 7.59, 7.49 4.56, 1.99 8.42, 7.5 0.88, 1.3 8.1, 7.56 1.99, 1.4 7.46, 7.57 1.96, 4.53 1.31, 0.89

(111)

111 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.75, 1.47 29.94, 1.27 119.81, 8.12 32.41, 2.01 47.8, 4.55 32.32, 1.26 123.35, 7.5 14.34, 0.89 27.75, 1.26 125.68, 7.58 18.13, 3.21 141.63, 7.86 22.39, 1.31 123.45, 8.44 Espectro 102. HSQC (400 MHz, CDCl3) do composto 44b.

(112)

112 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 26.4, 1.48 32.01, 1.47 26.49, 2.01 107.78, 3.2 120.64, 7.86 22.3, 0.89 107.67, 2.01 32.16, 3.21 144.37, 3.2 74.09, 3.21 74.24, 2 32.12, 0.89 141.24, 7.86 141.61, 4.54 77.1, 7.54 141.5, 8.12 77.36, 7.02 140.87, 3.21 120.42, 4.54 26.27, 4.54 125.72, 8.44 124.52, 7.49 29.88, 4.54 124.76, 8.12 47.38, 7.87 121.01, 8.44 119.42, 7.5 144.65, 8.44 Espectro 103. HMBC (400 MHz, CDCl3) do composto 44b.

(113)

113 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 4.53, 7.86 8.11, 4.53 1.47, 3.2 4.53, 8.12 1.99, 4.55 1.4, 4.54 1.97, 8.12 2.02, 3.2

(114)

114 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 Chemical Shift (ppm) 6.00 5.79 2.15 1.62 1.07 0.97 0.94 0.90 0.65 clorofórmio 0. 86 1. 27 1. 45 1. 48 1. 84 1. 99 2. 00 3. 21 3. 23 3. 25 4. 21 4. 23 4. 25 5. 04 5. 06 5. 42 5. 44 7. 28 7. 51 7. 63 7. 65 8. 11 8. 27 8. 30 8. 56 8. 59 8.5 8.0 7.5 Chemical Shift (ppm) 1.07 1.00 0.97 0.94 0.90 clorofórmio 8. 59 _8.56 _8.30 8.27 8.11 7. 65 7.63 _7.61 _7.52 7.51 7. 49 7. 28 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.00 5.96 3.88 2.15 1.98 AcOEt 3. 25 3.23 3. 21 2. 00 1.99 _1.97 1. 84 _1.48 1. 45 1. 27 0. 86 O N N C H3 CH3 CH3 CH3

(115)

115 152 144 136 128 120 112 104 96 88 80 72 64 56 48 40 32 24 16 Chemical Shift (ppm) 18 .37 19 .5 9 25 .69 26 .51 29 .7 1 32 .2 0 45 .7 7 73 .9 5 76 .7 2 77 .0 4 77 .24 77 .3 5 10 1. 43 11 3. 60 11 9.1 2 12 0. 69 12 1.7 5 12 2.5 1 12 4. 04 12 4.8 2 12 6. 80 12 7.0 5 12 8. 76 13 2. 87 13 8. 60 13 8.7 9 14 6. 75 145 140 135 130 125 120 Chemical Shift (ppm) 14 6. 75 13 8.7 9 13 8. 60 13 2. 87 12 8. 76 12 7.0 5 12 6. 80 12 4.8 2 12 4. 04 12 2.5 1 12 1.7 5 12 0. 69 11 9.1 2

(116)

116 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 5.45, 5.04 7.51, 8.28 3.21, 1.99 7.63, 8.58 1.94, 3.21 5.03, 1.82 8.57, 7.63 8.28, 7.5 7.63, 7.5 1.81, 5.04 5.44, 1.82 7.48, 7.63 1.8, 5.43 4.53, 2.58 6.87, 5.75 5.74, 6.88 2.57, 4.53

(117)

117 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 19.22, 3.22 118.82, 5.45 26.36, 1.47 18.15, 1.84 121.77, 8.58 45.84, 5.05 29.68, 1.27 25.5, 1.85 138.75, 8.11 32.19, 1.98 126.96, 7.63 122.32, 8.29 124.87, 7.51

(118)

118 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.67, 1.47 32.07, 1.48 26.04, 1.48 138.35, 1.83 118.47, 1.83 77.04, 7.02 76.97, 7.55 25.47, 1.84 18.18, 1.84 26.14, 1.99 101.31, 3.22 26.34, 1.32 138.31, 5.05 100.92, 1.98 31.98, 3.23 73.72, 3.23 146.45, 3.22 118.88, 5.05 73.61, 1.98 126.63, 8.28 128.69, 3.22 124.91, 7.63 121.64, 7.5 123.74, 7.51 124.13, 8.28 128.28, 5.04 146.76, 8.28 124.13, 8.58 130.32, 8.57

(119)

119 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 1.94, 1.47 3.23, 1.47 3.21, 5.04 5.05, 1.83 5.42, 5.04 5.43, 1.83 5.04, 8.11 8.12, 5.04 1.8, 5.04 1.47, 3.19 1.94, 3.21 1.78, 5.43 5.03, 5.42 5.03, 3.19 3.22, 1.98

(120)

120 8 7 17 14 16 15 13 5 9 6 N 12 11 N 10 4 3 2 O 1 CH₃ 18 C H₃ 19 20 21 22 C H₃ 23 CH₃ 24 (46b) M: 320.4281 Da [M+H]+ = 321.1961 Da; err[ppm] = -1,3

(121)

121 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 Chemical Shift (ppm) 6.47 3.54 2.69 1.96 2.09 2.19 1.071.00 1.00 AcOEt clorofórmio 1. 27 1. 48 1. 49 1. 85 1. 86 1. 87 1. 90 2. 01 2. 03 3. 19 3. 21 3. 22 3. 67 3. 76 3. 77 3. 79 3. 80 4. 19 4. 40 5. 07 5. 09 5. 23 5. 25 5. 52 5. 54 5. 55 7. 28 7. 56 7. 58 7. 60 7. 64 7. 65 8. 13 8. 15 8. 19 8. 21 8. 38 8. 44 8. 46 8. 49 8. 53 8. 56 8.5 8.0 7.5 Chemical Shift (ppm) 3.03 1.07 1.00 clorofórmio 8. 56 _8.53 8.49 8.46 8.44 8. 38 _8.30 8.28 8.21 8.19 8. 15 _8.13 _7.65 7.64 7.61 7.60 7.58 _7.56 7. 28 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.47 3.54 2.45 2.19 AcOEt 3. 22 3.21 _3.19 2. 03 2. 01 1.90 1.87 1. 86 _1.85 1. 49 1. 48 1. 27 Espectro 112. RMN-1H (400 MHz, CDCl3) do composto 46b.

(122)

122 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 18 .39 18 .49 18 .5 8 25 .77 26 .67 29 .7 1 31 .9 8 47 .0 5 61 .5 9 63 .7 5 69 .1 1 75 .3 2 76 .7 2 77 .0 4 77 .24 77 .3 5 10 5. 56 11 3. 78 11 6.8 9 12 0.2 9 12 0. 52 12 1. 06 12 3.6 4 12 4. 19 12 4.7 7 12 5. 00 12 6.6 6 12 8. 69 13 6. 17 13 7. 11 13 8.7 3 14 0. 74 14 6. 68 145 140 135 130 125 120 Chemical Shift (ppm) 14 6. 68 14 0. 74 13 8.7 3 13 7. 11 13 6. 17 12 8. 69 12 6.6 6 12 5. 00 12 4.7 7 12 4. 19 12 3.6 4 12 1. 06 12 0. 52 12 0.2 9 Espectro 113. RMN-13C (100 MHz, CDCl3) do composto 46b.

(123)

123 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 pp m 5.54, 5.23 7.64, 8.2 1.99, 3.21 7.56, 8.45 8.19, 7.63 8.47, 7.57 5.44, 5.07 5.23, 5.54 3.19, 2 5.07, 5.45 1.85, 5.53 5.53, 1.88 5.24, 1.88

(124)

124 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 29.48, 1.25 31.96, 2 25.66, 1.85 69.2, 4.19 73.46, 3.75 63.49, 3.76 46.99, 5.24 18.26, 1.89 17.92, 3.2 123.73, 8.46 116.83, 5.53 124.75, 7.58 61.32, 3.8 Espectro 115. HSQC (400 MHz, CDCl3) do composto 46b.

(125)

125 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 31.83, 1.47 26.4, 1.47 25.43, 1.9 26.49, 2.01 18.41, 1.87 140.79, 1.88 105.05, 3.2 124.91, 8.2 146.26, 3.2 73.87, 1.47 31.51, 3.21 175.05, 4.19 116.4, 1.88 104.74, 2.01 75.02, 3.2 126.95, 8.45 73.22, 4.19 116.36, 5.24 140.68, 5.25 74.39, 2.01 138.31, 5.24 124.61, 7.57 166.32, 4.4 123.44, 7.63 119.94, 7.57 136.16, 8.49 146.69, 8.46 Espectro 116. HMBC (400 MHz, CDCl3) do composto 46b.

(126)

126 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 pp m 8.2, 5.23 8.2, 7.63 5.23, 8.2 7.56, 8.46 7.61, 8.21 1.86, 5.53 1.89, 5.24 8.48, 5.23

(127)

127 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 25 24 26 23 22 (47a) M: 342.4337 Da [M+H]+ = 343.1805 Da; err[ppm] = -1,6

(128)

128 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 Chemical Shift (ppm) 6.08 4.63 2.00 1.99 2.05 1.96 1.04 1.00 0.95 0.94 1. 28 1. 38 1. 81 1. 83 1. 84 2. 94 2. 96 2. 97 5. 69 7. 00 7. 02 7. 29 7. 32 7. 34 7. 49 7. 51 7. 65 7. 67 8. 00 8. 28 8. 30 8. 63 8. 65 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.08 2.05 1.96 AcOEt 2. 97 2. 96 2. 94 1. 84 1. 83 1. 81 1. 38 1. 28 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 4.63 2.00 1.06 1.04 1.00 0.95 0.94 clorofórmio 8. 65 _8.63 8.30 8.28 8.00 7. 67 7.65 7. 63 _7.53 7.51 7. 49 7. 34 7. 32 7. 29 7. 02 7. 00

(129)

129 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 19 .10 26 .4 0 29 .72 32 .03 50 .79 61 .66 70 .54 73 .94 77 .2 5 10 1.5 4 12 1. 74 12 2. 52 12 4.0 9 12 4. 75 12 5.2 4 12 5. 68 12 8. 19 12 9.0 4 12 9. 23 13 6.8 9 14 0. 19 14 6.7 5 145 140 135 130 125 120 Chemical Shift (ppm) 14 6.7 5 14 0. 19 13 6.8 9 12 9. 23 12 9.0 4 12 8. 19 12 6. 99 12 5. 68 12 5.2 4 12 4. 75 12 4.0 9 12 2. 52 12 1. 74

(130)

130 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 7, 7.33 7.51, 8.28 7.32, 7.02 2.94, 1.82 1.79, 2.96 7.66, 7.52 7.63, 8.66 8.28, 7.52 8.66, 7.65

(131)

131 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.41, 1.37 50.58, 5.71 125.65, 7.02 129.25, 7.33 18.89, 2.95 31.9, 1.81 122.56, 8.28 124.71, 7.51 128.19, 7.31 121.67, 8.66

(132)

132 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.89, 1.38 26.14, 1.38 31.72, 1.38 76.97, 7.02 76.97, 7.55 125.65, 5.71 128.26, 7.02 31.72, 2.96 101.12, 1.83 73.76, 1.83 146.47, 2.96 73.76, 2.96 18.65, 1.82 136.59, 5.71 101.62, 2.96 124.09, 7.51 139.83, 5.71 128.37, 2.96 129, 5.71 125.52, 8.28 128.91, 1.48 136.62, 7.34 129.04, 7.33 146.65, 8.28 125, 7.65 121.61, 7.52 146.58, 1.38 50.7, 7.02

(133)

133 9 8 7 6 5 4 3 2 1 0 - 1 ppm - 1.0 - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 2.95, 5.71 5.7, 2.95

(134)

134 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 C H₃ 18 CH₃ 19 20 21 26 25 22 24 23 (47b) M: 342.4337 Da [M+H]+ = 343.1805 Da; err[ppm] = 0,4

(135)

135 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 Chemical Shift (ppm) 6.30 3.68 2.01 2.05 3.33 1.00 0.98 etanol actona etanol clorofórmio 1. 23 1. 40 1. 47 2. 00 2. 02 2. 16 3. 23 3. 25 3. 27 3. 72 5. 85 7. 16 7. 18 7. 29 7. 34 7. 36 7. 47 7. 49 7. 94 7. 96 8. 27 8. 38 8. 40 8.5 8.0 7.5 Chemical Shift (ppm) 3.68 2.26 1.00 0.98 0.98 clorofórmio 8. 40 8. 38 _8.27 7. 96 7. 94 7. 49 _7.47 _7.45 _7.42 7. 40 7.36 7. 34 7.29 7. 18 7. 16 Espectro 126. RMN-1H (400 MHz, CDCl3) do composto 47b.

(136)

136 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) etanol clorofórmio 18 .39 18 .5 8 26 .72 29 .7 1 32 .1 3 51 .8 0 58 .3 6 70 .5 3 75 .0 6 77 .0 6 77 .26 10 6. 52 12 0.2 3 12 0. 82 12 0. 92 12 3.3 7 12 4. 81 12 6.2 9 12 6.4 5 12 9.3 3 13 4. 83 13 8. 33 14 0.7 8 14 6. 19 145 140 135 130 125 120 Chemical Shift (ppm) 14 6. 19 14 0.7 8 13 8. 33 13 4. 83 12 9.3 3 12 8.4 5 12_6.4 5 12 6.2 9 12 4. 81 12 4.3 8 123.3₇ 12 0. 92 12 0. 82 12 0.2 3 Espectro 127. RMN-13C (100 MHz, CDCl3) do composto 47b.

(137)

137 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 1.22, 3.72 3.69, 1.23 7.34, 7.16 7.15, 7.36 7.41, 7.95 7.45, 8.39 3.24, 2.01 1.99, 3.25 7.94, 7.42 8.4, 7.46

(138)

138 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 58.13, 3.71 18.18, 1.24 26.33, 1.47 51.51, 5.85 31.9, 2.01 126.24, 7.16 129.15, 7.36 120.08, 7.95 123.09, 8.4 128.28, 7.33 126.17, 7.42 18.18, 3.25 Espectro 129. HSQC (400 MHz, CDCl3) do composto 47b.

(139)

139 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 75.34, 1.46 18.26, 3.73 26.67, 1.47 31.9, 1.46 125.91, 5.85 58.28, 3.91 77.23, 7.54 77.12, 7.02 134.55, 5.85 124.22, 7.96 26.45, 1.63 140.61, 5.85 58.06, 3.54 128.19, 7.18 105.83, 2.01 125.91, 8.4 74.65, 2 25.99, 2.01 106.02, 3.25 120.55, 7.41 51.5, 7.17 129.32, 7.36 18.02, 2.01 120.55, 8.4 146.06, 3.25 145.84, 8.4 126.78, 7.34 119.57, 7.47 120.55, 5.84 Espectro 130. HMBC (400 MHz, CDCl3) do composto 47b.

(140)

140 9 8 7 6 5 4 3 2 1 0 ppm - 0.5 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 7.95, 5.85 5.85, 7.95 7.14, 5.85 5.85, 7.17

(141)

141 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 C H₃ 18 CH₃ 19 20 21 O 23 O 22 24 C H₃ 25 (48a) M: 338.4004 Da [M+H]+ = 339.1703 Da; err[ppm] = -0,1

(142)

142 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 Chemical Shift (ppm) 6.04 2.24 2.08 2.03 2.02 1.01 1.00 1.00 0.60 clorofórmio 1. 26 1. 27 1. 29 1. 46 1. 96 1. 97 1. 99 3. 06 3. 07 3. 08 4. 25 4. 27 4. 28 4. 30 5. 15 7. 29 7. 49 7. 62 7. 63 7. 81 8. 28 8. 29 8. 55 8. 57 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 1.01 1.01 1.00 1.00 1.00 0.60 clorofórmio 8. 57 8. 55 _8.29 _8.28 7.81 7. 63 _7.62 _7.60 7. 50 _7.49 7. 47 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.04 4.06 2.24 2.03 3. 08 3. 07 3. 06 _1.99 1. 97 1. 96 1. 90 1. 46 1. 29 1. 27 1. 26

(143)

143 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .1 2 19 .29 26 .4 5 32 .18 48 .50 62 .26 73 .77 76 .79 10 1.1 8 12 1. 44 12 2. 45 12 3.8 1 12 4. 23 12 6.3 3 12 6. 65 12 9.1 9 13 3.0 1 14 0. 97 14 6.3 7 16 8.2 2 168 160 152 144 136 128 120 Chemical Shift (ppm) 16 8.2 2 14 6.3 7 14 0. 97 13 3.0 1 12 9.1 9 12 6. 65 12 6.3 3 12 4. 23 12 3.8 1 12 2. 45 12 1. 44

(144)

144 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.31, 1.45 48.19, 5.14 19.17, 3.06 32.22, 1.96 62.15, 4.26 14.02, 1.26 121.38, 8.56 122.32, 8.29 124.18, 7.49 126.32, 7.62 140.97, 7.8

(145)

145 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 160 168 176 184 192 200 pp m 73.78, 1.46 31.6, 1.46 25.97, 1.46 129.04, 5.14 140.61, 5.15 168.36, 5.14 26.06, 1.59 26.28, 1.97 26.67, 1.33 61.73, 1.26 146.21, 3.07 31.92, 3.07 73.63, 3.07 100.81, 1.96 73.91, 1.97 100.81, 3.07 129.15, 7.81 141, 8.02 129.08, 3.07 123.89, 8.56 13.75, 4.27 126.52, 8.29 77.17, 7.49 167.77, 4.27 77.28, 7.07 123.48, 7.49 121.46, 7.49 48.03, 7.81 146.26, 8.28 132.9, 8.56

(146)

146 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 pp m 3.04, 5.14 1.25, 4.26 5.15, 3.05

(147)

147 8 7 17 14 16 15 13 5 9 6 4 3 2 O 1 N 12 11 N 10 CH₃ 18 C H₃ 19 20 21 O 23 24 C H₃ 25 O 22 (48b) M: 338.4004 Da [M+H]+ = 339.1703 Da; err[ppm] = -0,4

(148)

148 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 Chemical Shift (ppm) 6.05 2.36 2.24 1.97 2.02 2.02 1.03 1.00 acetona clorofórmio 1. 23 1. 25 1. 26 1. 27 1. 48 1. 99 2. 01 2. 14 3. 21 3. 22 3. 24 4. 26 4. 27 4. 29 4. 31 5. 40 7. 29 7. 51 7. 53 7. 55 7. 91 7. 92 8. 37 8. 41 8. 42 8. 44 8.5 8.0 7.5 7.0 Chemical Shift (ppm) 2.24 1.03 1.00 clorofórmio 8. 44 _8.42 8. 41 8. 37 _7.92 _7.91 7. 57 7.55 7.53 7.53 7.51 7. 49 7. 29 3.0 2.5 2.0 1.5 1.0 Chemical Shift (ppm) 6.05 4.34 2.02 2.02 acetona 3. 24 3. 22 3. 21 2. 14 2. 03 2. 01 1. 99 1. 48 1. 27 1. 26 1. 25 1. 23 Espectro 139. RMN-1H (400 MHz, CDCl3) do composto 48b.

(149)

149 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 Chemical Shift (ppm) 14 .1 1 18 .47 26 .7 4 32 .23 49 .52 62 .44 74 .80 10 7.3 3 11 9. 18 12 0.9 5 12 1.1 2 12 3. 56 12 4.7 5 12 6. 12 13 9.5 7 14 1. 93 14 5.6 0 16 7.3 8 168 160 152 144 136 128 120 Chemical Shift (ppm) 16 7.3 8 14 5.6 0 14 1. 93 13 9.5 7 12 6. 12 12 4.7 5 12 4. 10 ₁₂3.56 12 1.1 2 12_0.9 5 11 9. 18 Espectro 140. RMN-13C (100 MHz, CDCl3) do composto 48b.

(150)

150 9 8 7 6 5 4 3 2 1 0 ppm 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 pp m 4.3, 1.22, 0.04 3.22, 1.99, 0.03 1.22, 4.29, 0.03 7.54, 7.91, 0.02 7.49, 8.43, 0.02 2, 3.22, 0.01 7.91, 7.54, 0.01

(151)

151 9 8 7 6 5 4 3 2 1 0 ppm - 8 0 8 16 24 32 40 48 56 64 72 80 88 96 104 112 120 128 136 144 152 pp m 26.34, 1.47 49.48, 5.38 32.07, 2.01 62.31, 4.28 123.27, 8.43 124.11, 7.52 13.81, 1.25 118.98, 7.92 18.16, 3.22 141.36, 8.28 Espectro 142. HSQC (400 MHz, CDCl3) do composto 48b.