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Linear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed, d Mahmoud E. S. Soliman, a Dilip D. Dhavale b, * and Thavendran Govender a, * a School of Pharmacy and Pharmacology, University of KwaZulu-Natal, South Africa b Garware Research Centre, Department of Chemistry, University of Pune, Pune, India c School of Chemistry, University of KwaZulu-Natal, South Africa d School of Molecular and Cell Biology, University of the Witwatersrand, Wits 2050, South Africa Supporting Information NMR Samples were dissolved in 500 µl of deuterated DMSO-d 6 and measured at 25 °C. All 1 H, 13 C, COSY, HMBC and HSQC NMR spectra, required for assignment were recorded on a Bruker AVANCE III 400 MHz spectrometer, BBO probe with z-gradient with standard parameters. The EASY-ROESY measurements required for structural analysis were recorded on a Bruker AVANCE III 600 MHz spectrometer using a BBO probe with z-gradient at a transmitter * * Corresponding author. Tel.: +91 (020) 25691727; fax: +91(020) 25691728 E-mail addresses: [email protected] (D.D. Dhavale). * Corresponding author. Tel.: +27 (031) 260 8212; fax: +27 (031) 260 7792 E-mail addresses: [email protected] (T. Govender).

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Page 1: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

Linear and cyclic glycopeptide as HIV protease inhibitors

Sachin A. Pawar,a Amit M. Jabgunde,b Glenn E. M. Maguire,c Hendrik G. Kruger,c Yasien Sayed, d

Mahmoud E. S. Soliman,a Dilip D. Dhavaleb, * and Thavendran Govendera, *

a School of Pharmacy and Pharmacology, University of KwaZulu-Natal, South Africab Garware Research Centre, Department of Chemistry, University of Pune, Pune, India

c School of Chemistry, University of KwaZulu-Natal, South Africad School of Molecular and Cell Biology, University of the Witwatersrand, Wits 2050, South Africa

Supporting Information

NMR

Samples were dissolved in 500 µl of deuterated DMSO-d6 and measured at 25 °C. All 1H,13C,

COSY, HMBC and HSQC NMR spectra, required for assignment were recorded on a Bruker

AVANCE III 400 MHz spectrometer, BBO probe with z-gradient with standard parameters. The

EASY-ROESY measurements required for structural analysis were recorded on a Bruker

AVANCE III 600 MHz spectrometer using a BBO probe with z-gradient at a transmitter

frequency of 600.1 MHz (spectral width, 10.0143 Hz; acquisition time, 0.1704436 s; 90°pulse

width, 11.02 µs; scans, 8; relaxation delay, 2.0 s, mixing time 0.25s, 2048 points in F2

dimensions). Processing and assignments were carried out using the Topspin 2.3 software from

Bruker Karlsruhe.

NMR elucidation of cyclic glycopeptide (6a)

** Corresponding author. Tel.: +91 (020) 25691727; fax: +91(020) 25691728E-mail addresses: [email protected] (D.D. Dhavale).* Corresponding author. Tel.: +27 (031) 260 8212; fax: +27 (031) 260 7792E-mail addresses: [email protected] (T. Govender).

Page 2: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

Supplementary Table 1:1H and 13C chemical shift of cyclic glycopeptide 6a as measured by

HSQC, COSY, HMBC, ROESY and 1H and 13C spectra. The chemical shift was referenced to

2.50 ppm for COSY and ROESY the correlation aided in assignment are marked in black and the

long-range interactions through space, measured by ROESY are marked in red.

Atom δ1Ha,b δ13Ca,d COSY (δ1Ha,b) HMBC ROESY (δ1Ha,c)

1 5.73 104.1 2 25 2,3,26

2 4.35 85.3 1 1,3,26

3 3.97 73.1 4 1,2,6a

4 4.45 80.3 3,5 3,5,6a,17,27

5 4.20 45.7 4,6a,6b 3,6a,6b

6a 2.30 36.1 5 7 3,4,5

6b 2.44 36.1 5 7 5

7 170.3

8 8.84 9

9 4.29 57.1 8,18 10 18,20a

10 171.5

11 8.08 12 14

12 3.81 60.5 11,21 13 14,21,22,23

13 170.6

14 8.26 15 13 11,12,15,17,21,24

15 4.16 47.7 14,24 13,16 14,17,24

16 169.8

17 6.76 16 4,14,15

18 2.94 36.3 9 10 9,20a

19 137.3

20a 7.24 128.8

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20b 7.27 128.2

20c 7.20 126.4

21 1.93 29.8 12,22,23 12,14

22 0.85 19.0 21 12,21

23 0.85 19.1 21 12,21

24 1.13 15.9 15 16 14,15

25 110.2

26 1.19 26.1 25 1,2

27 1.34 26.7 25 4

28 5.33

a Solvent (CD3)2SO.

b 400 MHz for 1H.

c 600 MHz for 1H.

d 100 MHz for 13C

NMR elucidation of linear glycopeptide (4a)

Supplementary Table 1:1H and 13C chemical shift of linear glycopeptide 4a as measured by

HSQC, COSY, HMBC, ROESY and 1H and 13C spectra. The chemical shift was referenced to

2.50 ppm for COSY and ROESY the correlation aided in assignment are marked in black and the

long-range interactions through space, measured by ROESY are marked in red.

Atom δ1Ha,b δ13Ca,d COSY (δ1Ha,b) HMBC ROESY (δ1Ha,c)

1 5.85 104.3 2 26 2,27

2 4.41 85.2 1,3 1,3,27

3 3.99 73.6 2 2,4,6a,6b,21b,27,28

4 3.93 80.5 5 3,5,28

Page 4: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

5 3.39 47.6 4,6a,6b 7 3,4

6a 2.31 36.3 5 7 3,6b

6b 2.55 36.1 5 7 3,6a

7 169.7

8 8.57 9

9 4.61 54.2 8,19a,19b 11,19a,19b,21a

10 171.2

11 8.17 12 9,12,22,23,24

12 4.15 57.8 11,22 10 11,14,22,23,24

13 169.8

14 7.88 15 12

15 3.97 48.7 14,25 16 25

16 174.6

17

18

19a 2.79 37.4 9 10 9,19b,21a

19b 3.04 37.4 9 9,19a,21a

20 137.8

21a 7.25 129.1 9,19a,19b

21b 7.24 128.0 3

21c 7.17 126.2

22 2.02 30.5 12,23,24 11,12,23,24

23 0.85 18.0 22 11,12,22

24 0.85 19.1 22 11,12,22

25 1.22 18.1 15 15

26 110.8

27 1.23 26.1 26 1,2,3

28 1.36 26.7 26 3,4

29

a Solvent (CD3)2SO.

b 400 MHz for 1H.

c 600 MHz for 1H.

d 100 MHz for 13C

Page 5: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 2a

Page 6: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 2a

Page 7: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 2a

Page 8: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 2b

Page 9: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 2b

Page 10: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 2b

Page 11: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 2c

Page 12: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 2c

Page 13: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 2c

Page 14: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 3a

Page 15: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 3a

Page 16: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 3a

Page 17: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 3b

Page 18: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 3b

Page 19: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 3b

Page 20: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 3c

Page 21: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 3c

Page 22: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

2b

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HRMS spectrum of compound 3c

Page 24: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 4a

Page 25: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 4a

Page 26: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 4a

Page 27: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 4b

Page 28: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 4b

Page 29: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 4b

Page 30: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 4c

13C NMR spectrum of compound 4c

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Page 32: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 4c

Page 33: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 5a

13C NMR spectrum of compound 5a

Page 34: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,
Page 35: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 5a

Page 36: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 5b

Page 37: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 5b

Page 38: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 5b

Page 39: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 5c

Page 40: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 5c

Page 41: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 5c

Page 42: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 6a

Page 43: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 6a

Page 44: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 6a

Page 45: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 6b

Page 46: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 6b

Page 47: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 6b

Page 48: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

1H NMR spectrum of compound 6c

Page 49: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

13C NMR spectrum of compound 6c

Page 50: ars.els-cdn.com · Web viewLinear and cyclic glycopeptide as HIV protease inhibitors Sachin A. Pawar, a Amit M. Jabgunde, b Glenn E. M. Maguire, c Hendrik G. Kruger, c Yasien Sayed,

HRMS spectrum of compound 6c