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