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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. 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: ddd@chem.unipune.ac.in (D.D. Dhavale).* Corresponding author. Tel.: +27 (031) 260 8212; fax: +27 (031) 260 7792E-mail addresses: govenderthav@ukzn.ac.za (T. Govender).

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

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

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

1H NMR spectrum of compound 2a

13C NMR spectrum of compound 2a

HRMS spectrum of compound 2a

1H NMR spectrum of compound 2b

13C NMR spectrum of compound 2b

HRMS spectrum of compound 2b

1H NMR spectrum of compound 2c

13C NMR spectrum of compound 2c

HRMS spectrum of compound 2c

1H NMR spectrum of compound 3a

13C NMR spectrum of compound 3a

HRMS spectrum of compound 3a

1H NMR spectrum of compound 3b

13C NMR spectrum of compound 3b

HRMS spectrum of compound 3b

1H NMR spectrum of compound 3c

13C NMR spectrum of compound 3c

2b

HRMS spectrum of compound 3c

1H NMR spectrum of compound 4a

13C NMR spectrum of compound 4a

HRMS spectrum of compound 4a

1H NMR spectrum of compound 4b

13C NMR spectrum of compound 4b

HRMS spectrum of compound 4b

1H NMR spectrum of compound 4c

13C NMR spectrum of compound 4c

HRMS spectrum of compound 4c

1H NMR spectrum of compound 5a

13C NMR spectrum of compound 5a

HRMS spectrum of compound 5a

1H NMR spectrum of compound 5b

13C NMR spectrum of compound 5b

HRMS spectrum of compound 5b

1H NMR spectrum of compound 5c

13C NMR spectrum of compound 5c

HRMS spectrum of compound 5c

1H NMR spectrum of compound 6a

13C NMR spectrum of compound 6a

HRMS spectrum of compound 6a

1H NMR spectrum of compound 6b

13C NMR spectrum of compound 6b

HRMS spectrum of compound 6b

1H NMR spectrum of compound 6c

13C NMR spectrum of compound 6c

HRMS spectrum of compound 6c