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1 Supporting Information Anti-Acanthamoeba activity of brominated sesquiterpenes from Laurencia johnstonii Sara García-Davis 1,2 , Ines Sifaoui 3 , María Reyes-Batlle 3 , Ezequiel Viveros-Valdez 2 , José E. Piñero 3 , Jacob Lorenzo-Morales 3 , José J. Fernández 1,4* and Ana R. Díaz-Marrero 1* 1 Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206 La Laguna, Tenerife, España; [email protected] (S.G.D.); [email protected] (A.R.D.M); [email protected] (J.J.F.) 2 Universidad Autónoma de Nuevo León (UANL), Facultad de Ciencias Biológicas. Av. Pedro de Alba s/n, 66450 San Nicolás de los Garza, Nuevo León, México; [email protected] (E.V.V.) 3 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Islas Canarias, Universidad de La Laguna. Av. Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Tenerife, España.; [email protected] (I.S.); [email protected] (J.L.M.) 4 Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206 La Laguna, Tenerife, España
23

Supporting Information - MDPI

Feb 14, 2022

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Page 1: Supporting Information - MDPI

1

Supporting Information

Anti-Acanthamoeba activity of brominated sesquiterpenes from Laurencia johnstonii

Sara García-Davis1,2, Ines Sifaoui3, María Reyes-Batlle3, Ezequiel Viveros-Valdez2, José E. Piñero3, Jacob Lorenzo-Morales3, José J. Fernández1,4* and Ana R. Díaz-Marrero1*

1 Instituto Universitario de Bio-Orgánica Antonio González (IUBO AG), Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206 La Laguna, Tenerife, España; [email protected] (S.G.D.); [email protected] (A.R.D.M); [email protected] (J.J.F.)

2 Universidad Autónoma de Nuevo León (UANL), Facultad de Ciencias Biológicas. Av. Pedro de Alba s/n, 66450 San Nicolás de los Garza, Nuevo León, México; [email protected] (E.V.V.)

3 Instituto Universitario de Enfermedades Tropicales y Salud Pública de Islas Canarias, Universidad de La Laguna. Av. Astrofísico Francisco Sánchez s/n, 38206 La Laguna, Tenerife, España.; [email protected] (I.S.); [email protected] (J.L.M.)

4 Departamento de Química Orgánica, Universidad de La Laguna (ULL), Avda. Astrofísico F. Sánchez, 2, 38206 La Laguna, Tenerife, España

Page 2: Supporting Information - MDPI

2

TABLE OF CONTENTS

Page Scheme S1. Isolation process of sesquiterpenes 1-5 from Laurencia johnstonii 3 Figure S1. 1H-NMR spectrum for laurinterol (1) (500 MHz, CDCl3) 4 Figure S2. 1H-NMR spectrum for isolaurinterol (2) (500 MHz, CDCl3) 5 Figure S3. 1H-NMR spectrum for aplysin (3) (500 MHz, CDCl3) 6 Figure S4. 1H-NMR spectrum for α-bromocuparane (4) (500 MHz, CDCl3) 7 Figure S5. 1H-NMR spectrum for α-isobromocuparane (5) (500 MHz, CDCl3) 8 Figure S6. 1H-NMR spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3) 9 Figure S7. COSY spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3) 10 Figure S8. HSQC-ed spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3) 11 Figure S9. HMBC spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3) 12 Figure S10. 13C NMR spectrum of 8-bromoaplysin (6) (150 MHz, CDCl3) 13 Figure S11. HREIMS spectrum of 8-bromoaplysin (6) 14 Figure S12. 1H NMR spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3) 15 Figure S13. COSY spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3) 16 Figure S14. HSQC-ed spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3) 17 Figure S15. HMBC spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3) 18 Figure S16. 13C NMR spectrum of 3a-bromojohnstane (7) (150 MHz, CDCl3) 19 Figure S17. 1D-NOE experiments of 3a-bromojohnstane (7) (600 MHz, CDCl3) 20 Figure S18. HREIMS spectrum of 3a-bromojohnstane (7) 21 Figure S19. 1H NMR spectrum of 8,10-dibromoisoaplysin (8) (500 MHz, CDCl3) 22 Figure S20. 1H NMR spectrum of 8,10-dibromoaplysinol (9) (500 MHz, CDCl3) 23

Page 3: Supporting Information - MDPI

3

Scheme S1. Isolation process of sesquiterpenes 1-5 from Laurencia johnstonii

Br

OH

laurinterol (1)

Br

OH

isolaurinterol (2)

Br

O

aplysin (3)

α-bromocuparane (4)

Br

α-isobromocuparane (5)

Br

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4

Figure S1. 1H-NMR spectrum for laurinterol (1) (500 MHz, CDCl3).

012345678

G9

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5

Figure S2. 1H-NMR spectrum for isolaurinterol (2) (500 MHz, CDCl3).

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6

Figure S3. 1H-NMR spectrum for aplysin (3) (500 MHz, CDCl3).

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7

Figure S4. 1H-NMR spectrum for α-bromocuparane (4) (500 MHz, CDCl3).

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8

Figure S5. 1H-NMR spectrum of α-isobromocuparane (5) (500 MHz, CDCl3).

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9

Figure S6. 1H-NMR spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3).

0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

Page 10: Supporting Information - MDPI

10

Figure S7. COSY spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3).

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f2(ppm)

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

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

Page 11: Supporting Information - MDPI

11

Figure S8. HSQC-ed spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.07.5f2(ppm)

10

20

30

40

50

60

70

80

90

100

110

120

130

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

Page 12: Supporting Information - MDPI

12

Figure S9. HMBC spectrum of 8-bromoaplysin (6) (600 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.07.5

f2(ppm)

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

Page 13: Supporting Information - MDPI

13

Figure S10. 13C NMR spectrum of 8-bromoaplysin (6) (150 MHz, CDCl3).

102030405060708090100110120130140150160f1(ppm)

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14

Figure S11. HREIMS spectrum of 8-bromoaplysin (6).

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15

Figure S12. 1H NMR spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3).

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

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16

Figure S13. COSY spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.07.5

f2(ppm)

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

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

Page 17: Supporting Information - MDPI

17

Figure S14. HSQC-ed spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.0

f2(ppm)

10

20

30

40

50

60

70

80

90

100

110

120

130

140

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

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18

Figure S15. HMBC spectrum of 3a-bromojohnstane (7) (600 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.0

f2(ppm)

20

30

40

50

60

70

80

90

100

110

120

130

140

150

160

170

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

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19

Figure S16. 13C NMR spectrum of 3a-bromojohnstane (7) (150 MHz, CDCl3).

102030405060708090100110120130140150160

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

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20

Figure S17. 1D-NOE experiments of 3a-bromojohnstane (7) (600 MHz, CDCl3).

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.5f1(ppm)

H4 – SELECTIVE NOESY PULSE AT dH 3.84 ppm

H14 – SELECTIVE NOESY PULSE AT dH 1.04 ppm

H13/H5b – SELECTIVE NOESY PULSE AT dH 1.54 ppm

H3-13

H3-13

H3-14H-6a/H-5b

H-12

H-4

H-3b

H-6a

H-3b

Br

OBr

Br14

COSY

14

1513

2

11

9

7

H

HMBC

H4

Me13

Me14

H3β

(a) (b)

H6β

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21

Figure S18. HREIMS spectrum of 3a-bromojohnstane (7).

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22

Figure S19. 1H NMR spectrum of 8,10-dibromoisoaplysin (8) (500 MHz, CDCl3).

1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14

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23

Figure S20. 1H NMR spectrum of 8,10-dibromoaplysinol (9) (500 MHz, CDCl3).

0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0

f1(ppm)

Br

OH

laurinterol (1)

Br

OBr

Br

OBr

Br

8

6 (15%) 3α-bromojohnstane (7) (30%)

Br

OH

isolaurinterol (2)

Br

OBr

6 (24%)

Br

OBr Br

Br

OBr OH

8 (6%) 9 (27%)

13

5

6

1312

14

15

24

17

14

1315 9

11

Br2 (1.95 mmol)

Et2O, rt, 15 min

Br2 (1.95 mmol)

Et2O, rt, 15 min

HBr (10 µL, 48%)

Et2O, rt, 15 min

Br

O8

13

5

6

1312

14