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New Flavonoids from the Saudi Arabian Plant Retama raetam which Stimulate Secretion of Insulin and Inhibit -Glucosidase)
Muhammad Yousaf,a Mohammad Nur-e-Alam,*,a Ifat Parveen,b Rahman M. Hafizur,c Usman Ghani,d Sarfaraz Ahmed,a Abdul Hameed,c Michael D. Threadgille and Adnan J. Al-Rehaily*,a
a Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box. 2457, Riyadh 11451, Kingdom of Saudi Arabia
b Institute of Biological, Environmental & Rural Sciences (IBERS), Aberystwyth University, Aberystwyth SY23 3DA, United Kingdom
c Clinical Biochemistry Unit, Department of Pathology, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia
d Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan
e Drug & Target Discovery, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
ContentsFig. S1: HRMS of 1
Fig. S2: 1H NMR spectrum of 1
Fig. S3: Expansion of 1H NMR spectrum of 1
Fig. S4: 13C NMR spectrum of 1
Fig. S5: COSY spectrum of 1
Fig. S6: HMBC spectrum of 1
Fig. S7: HSQC spectrum of 1
Fig. S8: HRMS of 2
Fig. S9: 1H NMR spectrum of 2
Fig. S10: Expansion A of 1H NMR spectrum of 2
Fig. S11: Expansion B of 1H NMR spectrum of 2
Fig. S12: 13C NMR spectrum of 2
Fig. S13: COSY spectrum of 2
Fig. S14: HMBC spectrum of 2
Fig. S15: HSQC spectrum of 2
Fig. S16: NOESY spectrum of 2
Fig. S17: HRMS of 3
Fig. S18: 1H NMR spectrum of 3
Fig. S19: Expansion of 1H NMR spectrum of 3
Fig. S20: 13C NMR spectrum of 3
Fig. S21: COSY spectrum of 3
Fig. S22: HMBC spectrum of 3
Fig. S23: HSQC spectrum of 3
Fig. S24: NOESY spectrum of 3
Fig. S25: 1H NMR spectrum of 4
Fig. S26: Expansion of 1H NMR spectrum of 4
Fig. S27: 13C NMR spectrum of 4
Fig. S28: COSY spectrum of 4
Fig. S29: HMBC spectrum of 4
Fig. S30: HSQC spectrum of 4
Fig. S31: HRMS of compound 5
Fig. S32: 1H NMR spectrum of 5
Fig. S33: Expansion of 1H NMR spectrum of 5
Fig. S34: 13C NMR spectrum of 5
Fig. S35: COSY spectrum of 5
Fig. S36: HMBC spectrum of 5
Fig. S37: HSQC spectrum of 5
Fig. S38: NOESY spectrum of 5
Fig. S39: HRMS of 6
Fig. S40: 1H NMR spectrum of 6
Fig. S41: Expansion of 1H NMR spectrum of 6
Fig. S42: 13C NMR spectrum of 6
Fig. S43: COSY spectrum of 6
Fig. S44: HMBC spectrum of 6
Fig. S45: HSQC spectrum of 6
Fig. S46: NOESY spectrum of 6
Fig. S47: HRMS of 7
Fig. S48: 1H NMR spectrum of 7
Fig. S49: 13C NMR spectrum of 7
Fig. S50: COSY spectrum spectrum of 7
Fig. S51: HMBC spectrum of 7
Fig. S52: HSQC spectrum of 7
Fig. S53: HRMS of 8
Fig. S54: 1H NMR spectrum of 8
Fig. S55: Expansion A of 1H NMR spectrum of 8
Fig. S56: Expansion B of 1H NMR spectrum of 8
Fig. S57: 13C NMR spectrum of 8
Fig. S58: COSY spectrum of 8
Fig. S59: HMBC spectrum of 8
Fig. S60: HSQC spectrum of 8
Fig. S61: 1H NMR spectrum of 9
Fig. S62: Expansion of 1H NMR spectrum of 9
Fig. S63: 13C NMR spectrum of 9
Fig. S64: COSY spectrum of 9
Fig. S65: HMBC spectrum of 9
Fig. 66: HSQC spectrum of 9
Fig. 67: 1H NMR spectrum of 10
Fig. 68: Expansion of 1H NMR spectrum of 10
Fig. 69: 13C NMR spectrum of 10
Fig. 70: COSY spectrum of 10
Fig. 71: HMBC spectrum of 10
Fig. 72: HSQC spectrum of 10
Fig. S73: CD spectrum of 2
Fig. S74: CD spectrum of 5
Fig. S75: CD spectrum of 8
Table S1: 1H and 13C NMR spectroscopic data for 4,9,10 in (CD3)2SO [H, multiplicity (J (Hz)); C, type]
Table S2: Insulin secretion data
Fig. S1. HRMS of 1
150 200 250 300 350 400 450 500 550 600 650 700 750 800m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e A
bund
ance
353.1018
389.0794 743.1894707.2125
170.8320 416.0982337.0713 753.2179283.2637 467.0948199.0237 797.2442691.1810613.5402519.1287 557.1652355.1156
191.0918
169.1099
377.0982 537.3928253.0621 709.2250
205.0318
437.3161339.0851 507.3272 551.3531 595.3791 635.1954 812.2497745.1858
NL: 6.23E6R16#139-173 RT: 1.21-1.77 AV: 27 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 3.84E7R16#16-96 RT: 0.13-0.76 AV: 28 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S2. 1H NMR spectrum of 1
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.513.514.5f1 (ppm)
5.97
0.96
4.07
1.94
0.96
1.11
2.14
2.11
1.00
1.18
45
2.51
19
3.17
943.
2929
3.30
993.
3345
4.73
844.
8004
6.28
16
6.80
326.
9429
6.95
92
7.93
697.
9530
13.1
896
Fig. S3. Expansion of 1H NMR spectrum of 1
3.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)
0.96
4.07
1.94
0.96
1.11
2.14
2.11
3.17
943.
2929
3.30
993.
3345
4.73
844.
8004
6.28
16
6.80
32
6.94
296.
9592
7.93
697.
9530
Fig. S4. 13C NMR spectrum of 1
102030405060708090100110120130140150160170180190200f1 (ppm)
25.3
526
.25
26.4
939
.61
39.7
339
.85
39.9
740
.09
40.2
040
.32
49.0
7
70.5
3
92.0
593
.95
103.
2210
4.48
104.
68
116.
49
121.
52
128.
94
152.
20
161.
7816
2.28
163.
8116
6.74
182.
30
Fig. S5. COSY spectrum of 1
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
1
2
3
4
5
6
7
8
f1 (
ppm
)
Fig. S6. HMBC spectrum of 1
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (
ppm
)
Fig. S7. HSQC spectrum of 1
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
f1 (
ppm
)
150 200 250 300 350 400 450 500 550 600 650 700 750 800m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e A
bund
ance
353.1023
743.1893
389.0793707.2126
397.1286787.2154
416.0982251.0557
751.2383
279.1632 467.0950191.0187335.0923
137.0230 699.1266511.1214
361.1783
633.2732605.1658557.3362
355.1161191.0917
155.0629
253.0621
180.0946
377.0982 537.3932237.0846337.1132 437.3163 465.3475
205.0319
729.1913281.0866 545.1881 621.4440 683.5407 769.2163
NL: 1.56E8R17#156-263 RT: 1.19-1.78 AV: 26 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 6.87E7R17#21-109 RT: 0.13-0.78 AV: 28 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S8. HRMS of 2
Fig. S9. 1H NMR spectrum of 2
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.0f1 (ppm)
5.28
0.95
1.12
1.06
0.94
1.14
1.79
1.82
1.00
1.23
851.
2912
1.31
892.
4669
2.47
102.
4754
2.47
982.
4844
2.50
822.
5092
2.51
022.
5143
2.51
532.
9680
2.96
883.
3016
3.74
63
5.28
52
6.13
42
6.82
136.
9193
6.94
12
7.90
817.
9301
12.6
991
5.85.96.06.16.26.36.46.56.66.76.86.97.07.17.27.37.47.57.67.77.87.98.08.18.28.38.4f1 (ppm)
0.94
1.14
1.79
1.82
6.13
42
6.82
13
6.91
936.
9412
7.90
817.
9301
Fig. S10. Expansion A of 1H NMR spectrum of 2
1.01.11.21.31.41.51.61.71.81.92.02.12.22.32.42.52.62.72.82.93.03.13.23.33.43.53.63.7f1 (ppm)
5.28
0.95
1.12
1.23
851.
2912
1.31
89
2.46
692.
4710
2.47
542.
4798
2.48
442.
5042
2.50
522.
5062
2.50
722.
5082
2.50
922.
5102
2.51
432.
5153
2.51
922.
5202
2.52
122.
5222
2.69
872.
7157
2.73
992.
7569
2.96
802.
9688
3.02
303.
0357
3.06
413.
0770
3.30
16
3.74
63
Fig. S11. Expansion B of 1H NMR of 2
Fig. S12. 13C NMR spectrum of 2
102030405060708090100110120130140150160170180190f1 (ppm)
21.5
325
.32
25.6
1
39.6
039
.72
39.8
439
.96
40.0
840
.20
40.3
2
67.2
8
79.4
4
99.4
999
.79
103.
5010
4.98
116.
53
121.
74
128.
85
154.
8215
9.29
159.
3516
1.77
164.
00
182.
43
Fig. S13. COSY spectrum of 2
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
Fig. S14. HMBC spectrum of 2
12345678910111213f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
f1 (
ppm
)
Fig. S15. HSQC spectrum of 2
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
f1 (
ppm
)
Fig. S16. NOESY spectrum of 2
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f2 (ppm)
1
2
3
4
5
6
7
8
9
f1 (
ppm
)
Fig. S17. HRMS of 3
150 200 250 300 350 400 450 500 550 600 650 700 750 800 850m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e A
bund
ance
353.1020
383.1132
707.2126 743.1894265.1476 393.2773309.1738255.2326 803.2103170.8320 619.2573446.1085 663.2838482.1448
693.3095833.2209585.5092539.5037
355.1159
385.1264
191.0917
169.1099 545.4212331.2829 711.5714515.4108437.3160200.2366 261.1300 739.6026305.1558 595.3790
409.1605
639.4050 771.5710
678.4757
815.5089
NL: 3.52E8R12#253-391 RT: 1.21-1.81 AV: 24 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 1.47E8R12#42-161 RT: 0.26-0.76 AV: 20 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S18. 1H NMR spectrum of 3
-2-101234567891011121314f1 (ppm)
2.43
2.33
0.72
0.67
1.60
1.20
1.00
1.02
301.
0402
1.20
93
2.46
682.
4711
2.47
572.
4802
2.48
48
3.29
703.
3905
3.85
633.
9099
6.23
11
6.73
016.
8633
6.88
53
7.80
597.
8279
12.9
217
Fig. S19. Expansion of 1H NMR spectrum of 3
4.04.55.05.56.06.57.07.58.0f1 (ppm)
2.33
0.72
0.67
1.60
1.20
3.85
633.
9099
6.23
11
6.73
01
6.86
336.
8853
7.80
597.
8279
Fig. S20. 13C NMR spectrum of 3
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f2 (ppm)
1
2
3
4
5
6
7
8
f1 (
ppm
)
102030405060708090100110120130140150160170180190200210f1 (ppm)
18.8
1
35.2
2
56.3
2
98.9
910
1.38
103.
4610
3.99
116.
45
121.
97
128.
97
155.
5216
0.22
161.
7916
4.18
182.
36
211.
53
Fig. S21. COSY spectrum of 3
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (p
pm)
01234567891011121314 f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (ppm)
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (p
pm)
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (p
pm)
Fig. S22. HMBC spectrum of 3
Fig. S23. HSQC spectrum of 3
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
f1 (
ppm
)
Fig. S24. NOESY spectrum of 3
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
1
2
3
4
5
6
7
8
f1 (
ppm
)
Fig. S25. 1H NMR spectrum of 4
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.013.5f1 (ppm)
3.05
3.15
2.50
1.04
0.99
1.06
2.08
2.11
1.00
1.63
871.
7702
2.51
35
3.36
363.
4443
3.45
33
5.20
33
6.29
36
6.78
716.
9391
6.95
13
7.90
917.
9212
12.9
135
Fig. S26. Expansion of 1H NMR spectrum of 4
3.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.67.88.08.2f1 (ppm)
2.50
1.04
0.99
1.06
2.08
2.11
3.36
363.
4443
3.45
33
5.20
33
6.29
36
6.78
71
6.93
916.
9513
7.90
917.
9212
102030405060708090100110120130140150160170180f1 (ppm)
18.3
021
.81
25.9
3
39.6
139
.72
39.8
439
.96
40.0
840
.20
40.3
240
.46
98.8
210
3.13
104.
0810
6.55
116.
46
121.
9912
2.95
128.
8213
1.47
154.
95
159.
5216
1.62
162.
0816
4.12
182.
54
Fig. S27. 13C NMR spectrum of 4
Fig. S28. COSY spectrum of 4
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f2 (ppm)
2
3
4
5
6
7
8
f1 (
ppm
)
Fig. S29. HMBC spectrum of 4
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (
ppm
)
Fig. S30. HSQC spectrum of 4
1.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
f1 (
ppm
)
150 200 250 300 350 400 450 500 550 600 650 700 750 800m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100R
elat
ive
Abu
ndan
ce403.0585
367.0818
771.1479413.0874
491.1473 787.1791455.1706170.8321 263.0988 339.0869
421.0869
803.2103587.1032279.1633 743.1530187.0965 227.1217 518.1659 631.1878 703.1217369.0953
191.0917 391.0772
537.3927
737.1833353.2648
407.1085 759.1652155.1537335.2179
545.4211217.1362 259.1466 441.2957775.1963229.1362 475.1285
515.4107
572.1129 721.3527 791.2275277.1817 621.4438 683.5403
NL: 1.10E8R14#245-388 RT: 1.22-1.82 AV: 24 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 6.37E7R14#26-158 RT: 0.14-0.73 AV: 23 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S31. HRMS of 5
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.013.5f1 (ppm)
3.13
0.97
0.96
0.95
0.95
1.08
1.12
2.48
2.36
1.06
1.15
1.00
1.50
34
2.51
302.
5279
2.55
242.
6084
3.35
24
3.90
433.
9190
4.04
954.
0641
4.16
644.
1718
5.02
01
5.90
135.
9069
6.49
48
6.82
786.
8399
7.38
237.
3943
8.39
37
9.64
24
13.3
659
Fig. S32. 1H NMR spectrum of 5
Fig. S33. Expansion of 1H-NMR spectrum of 5
3.84.04.24.44.64.85.05.25.45.65.86.06.26.46.66.87.07.27.47.6f1 (ppm)
0.97
0.96
0.95
0.95
1.08
1.12
2.48
2.36
3.90
433.
9190
4.04
954.
0641
4.16
644.
1718
5.02
01
5.90
135.
9069
6.49
48
6.82
786.
8399
7.38
237.
3943
Fig. S34. 13C NMR spectrum of 5
102030405060708090100110120130140150160170180f1 (ppm)
16.3
9
73.0
373
.90
77.0
1
88.3
8
94.1
3
105.
51
109.
85
115.
56
121.
4112
2.85
130.
65
154.
9315
7.53
157.
6615
8.02
160.
19
180.
96
Fig. S35. COSY spectrum of 5
1.01.52.02.53.03.54.04.55.05.56.06.57.07.5f2 (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
8.0
f1 (
ppm
)
Fig. S36. HMBC spectrum of 5
2345678910111213f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
f1 (
ppm
)
Fig. S37. HSQC spectrum of 5
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.0f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
f1 (
ppm
)
Fig. S38. NOESY spectrum of 5
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0f2 (ppm)
1
2
3
4
5
6
7
8
9
10
f1 (
ppm
)
Fig. S39. HRMS of 6
150 200 250 300 350 400 450 500 550 600 650 700 750 800m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e A
bund
ance
369.0970
403.0585
413.0873
771.1478170.8321
311.1684265.1477
337.1079
432.0929 735.1713215.0320783.1921
483.0898 587.1032 825.2028651.3529539.1376 695.2879191.0917
169.1099
369.0954
391.0772
759.1651253.0620 475.1285295.0590 737.1832422.3915338.3403 545.4212217.1039 595.3791 675.6733 775.1389 843.2039
NL: 1.77E8R13#263-389 RT: 1.24-1.79 AV: 22 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 2.56E8R13#33-172 RT: 0.18-0.79 AV: 24 T: FTMS + p NSI Full ms [113.40-1700.00]
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.013.5f1 (ppm)
3.11
1.29
1.60
1.11
0.94
1.37
0.83
2.14
2.03
1.00
1.31
1.11
1.29
23
2.47
102.
4754
2.47
982.
4842
2.51
412.
5153
3.14
663.
1678
3.29
713.
4136
3.43
48
4.75
814.
7723
5.23
82
5.70
185.
7160
6.58
786.
7926
6.79
756.
8094
6.81
397.
3572
7.36
197.
3785
8.37
78
9.58
26
13.4
657
Fig. S40. 1H NMR spectrum of 6
Fig. S41. Expansion of 1H NMR of 6
3.03.54.04.55.05.56.06.57.07.5f1 (ppm)
1.29
1.60
1.11
0.94
1.37
0.83
2.14
2.03
3.14
663.
1678
3.29
713.
4136
3.43
48
4.75
814.
7723
5.23
82
5.70
185.
7160
6.58
78
6.79
266.
7975
6.80
946.
8139
7.35
727.
3619
7.37
85
Fig. S42. 13C NMR spectrum of 6
102030405060708090100110120130140150160170180190f1 (ppm)
25.1
2
39.6
139
.73
39.8
539
.97
40.0
940
.21
40.3
340
.46
40.8
7
72.7
977
.08
78.6
8
89.4
491
.91
106.
2210
9.10
115.
56
121.
3612
2.76
130.
67
154.
8615
7.99
158.
9115
9.28
167.
38
181.
30
Fig. S43. COSY spectrum of 6
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
1
2
3
4
5
6
7
8
f1 (
ppm
)
Fig. S44. HMBC spectrum of 6
01234567891011121314f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (
ppm
)
Fig. S45. HSQC spectrum of 6
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
f1 (
ppm
)
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.5f2 (ppm)
1
2
3
4
5
6
7
8
9
f1 (
ppm
)
Fig. S46. NOESY of 6
Fig. S47. HRMS of 7
150 200 250 300 350 400 450 500 550 600 650 700 750 800m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100R
elat
ive
Abu
ndan
ce
365.0659
381.0611
393.2774 767.1164170.8321 355.1184 731.1399311.1684265.1476 574.0887413.0873 491.1471187.0965 821.2442677.2418631.2211521.1577545.4216
191.0919
367.0800
353.2650242.2835169.1100
515.4113405.0568 755.1344473.1132331.2831261.1302214.2523 595.3793 639.4052 719.3373
553.3876
787.1234
NL: 1.68E8R15#177-316 RT: 1.24-1.84 AV: 24 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 4.38E7R15#15-127 RT: 0.13-0.77 AV: 27 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S48. 1H NMR spectrum of 7
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.513.5f1 (ppm)
5.44
1.03
1.11
3.54
4.68
1.48
1.77
0.87
1.00
1.26
03
1.87
25
2.47
522.
5187
2.61
24
3.31
353.
3559
6.35
646.
4570
6.83
816.
8414
7.38
557.
3952
8.37
25
9.64
83
13.7
271
Fig. S49. 13C NMR spectrum of 7
102030405060708090100110120130140150160170180f1 (ppm)
10.8
2
40.8
9
74.1
6
93.9
0
104.
11
115.
58
121.
4412
2.87
128.
4813
0.70
149.
15
154.
7015
7.72
158.
0016
1.73
167.
59
175.
03
180.
94
Fig. S50. COSY spectrum of 7
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
0
1
2
3
4
5
6
7
8
f1 (
ppm
)
Fig. S51. HMBC spectrum of 7
0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (
ppm
)
Fig. S52. HSQC spectrum of 7
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
140
150
f1 (
ppm
)
Fig. S53. HRMS of 8
150 200 250 300 350 400 450 500 550 600 650 700 750 800 850 900m/z
0
10
20
30
40
50
60
70
80
90
1000
10
20
30
40
50
60
70
80
90
100
Rel
ativ
e A
bund
ance
429.1105
393.1340
439.1394
365.2459
823.2519297.0401
279.1632170.8321 833.2807265.1477 311.1684
483.2017 787.2752
347.1991
187.0965 727.1581626.1812 677.4050519.1782 585.5093 850.2705
449.1235
395.1473
789.2872
191.0918
537.3928417.1292
811.2690353.2648242.2834
381.2960
515.4109437.3161200.2366 331.2830 603.2021 867.6682747.4047261.1300
775.4359
711.5717551.3532
639.4050
NL: 1.01E8R10#183-321 RT: 1.24-1.81 AV: 23 T: FTMS - p NSI Full ms [113.40-1700.00]
NL: 1.04E8R10#23-128 RT: 0.18-0.81 AV: 27 T: FTMS + p NSI Full ms [113.40-1700.00]
Fig. S54. 1H NMR spectrum of 8
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.513.5f1 (ppm)
2.97
3.65
1.46
1.15
1.21
1.00
1.10
2.01
2.00
1.18
1.11
1.00
1.02
631.
0383
1.41
101.
6724
1.68
411.
8105
1.82
75
2.37
312.
5116
2.55
112.
6462
3.33
313.
5566
4.40
354.
4100
4.41
87
5.73
275.
7529
6.49
336.
6534
6.67
406.
8260
6.84
27
7.38
357.
4001
8.37
49
9.61
50
13.3
795
Fig. S55. Expansion A of 1H NMR spectrum of 8
3.54.04.55.05.56.06.57.07.5f1 (ppm)
1.46
1.15
1.21
1.00
1.10
2.01
2.00
3.33
31
3.55
66
4.40
354.
4100
4.41
87
5.73
275.
7529
6.49
33
6.65
346.
6740
6.82
606.
8427
7.38
357.
4001
Fig. S56. Expansion B of 1H NMR spectrum of 8
0.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.6f1 (ppm)
2.97
3.65
1.46
1.15
1.02
631.
0383
1.41
10
1.65
421.
6724
1.68
411.
7828
1.81
051.
8275
1.86
65
2.37
31
2.51
162.
5511
2.64
62
3.33
31
3.55
66
4.40
354.
4100
4.41
87
Fig. S57. 13C NMR spectrum of 8
102030405060708090100110120130140150160170180f1 (ppm)
24.1
7
27.4
0
33.6
6
37.9
6
66.2
8
81.1
0
94.8
5
105.
0210
5.76
115.
4111
5.45
115.
54
121.
4812
2.87
128.
5312
8.57
130.
65
154.
7315
6.37
157.
2115
7.96
159.
72
180.
91
Fig. S58. COSY spectrum of 8
1.01.52.02.53.03.54.04.55.05.56.06.57.07.5f2 (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
)
Fig. S59. HMBC spectrum of 8
-0.50.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (ppm)
0
20
40
60
80
100
120
140
160
180
200
f1 (
ppm
)
Fig. S60. HSQC spectrum of 8
1.01.52.02.53.03.54.04.55.05.56.06.57.07.5f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
f1 (
ppm
)
Fig. S61. 1H NMR spectrum of 9
0.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.511.512.513.5f1 (ppm)
3.10
2.31
2.07
0.95
0.94
0.89
0.97
1.95
2.07
1.01
1.05
1.00
1.35
51
2.51
35
3.37
513.
4869
3.49
543.
5035
5.13
01
5.73
255.
7470
6.47
106.
6821
6.69
656.
8305
6.84
23
7.38
587.
3976
8.36
54
9.63
62
13.3
559
Fig. S62. Expansion of 1H NMR spectrum of 9
3.54.04.55.05.56.06.57.07.5f1 (ppm)
2.31
2.07
0.95
0.94
0.89
0.97
1.95
2.07
3.37
513.
4869
3.49
543.
5035
5.13
01
5.73
255.
7470
6.47
10
6.68
216.
6965
6.83
056.
8423
7.38
587.
3976
Fig. S63. 13C NMR spectrum of 9
2030405060708090100110120130140150160170180f1 (ppm)
23.6
9
39.6
039
.72
39.8
439
.96
40.0
840
.20
40.3
240
.45
67.5
0
81.6
6
94.9
4
105.
2610
5.74
115.
5411
6.47
121.
4912
2.85
126.
6913
0.64
154.
6715
6.30
157.
1415
7.95
159.
72
180.
88
Fig. S64. COSY spectrum of 9
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f2 (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
8.0
f1 (
ppm
)
Fig. S65. HMBC spectrum of 9
1234567891011121314f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
190
f1 (
ppm
)
Fig. S66. HSQC spectrum of 9
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
140
150
f1 (
ppm
)
Fig. S67. 1H NMR spectrum of 10
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.010.511.011.512.012.513.013.514.014.5f1 (ppm)
10.7
5
1.72
5.21
4.70
1.18
1.51
1.00
1.54
49
2.51
262.
5518
2.60
82
3.34
93
5.51
53
6.80
836.
8468
6.85
90
7.41
767.
4286
7.44
07
8.51
73
9.64
08
13.7
378
Fig. S68. Expansion of 1H NMR spectrum of 10
4.74.84.95.05.15.25.35.45.55.65.75.85.96.06.16.26.36.46.56.66.76.86.97.07.17.27.37.47.57.67.77.8f1 (ppm)
1.72
5.21
4.70
5.51
53
6.80
836.
8468
6.85
90
7.41
767.
4286
7.44
07
Fig. S69. 13C NMR spectrum of 10
2030405060708090100110120130140150160170180f1 (ppm)
29.2
5
67.8
8
91.2
4
97.6
8
106.
39
113.
6311
5.57
121.
5512
2.02
130.
74
153.
9015
4.66
155.
6515
7.93
158.
52
165.
59
182.
59
Fig. S70. COSY spectrum of 10
2.53.03.54.04.55.05.56.06.57.07.5f2 (ppm)
2.5
3.0
3.5
4.0
4.5
5.0
5.5
6.0
6.5
7.0
7.5
f1 (
ppm
)
Fig. S71. HMBC spectrum of 10
1.52.02.53.03.54.04.55.05.56.06.57.07.5f2 (ppm)
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
160
170
180
f1 (
ppm
)
Fig. S72. HSQC spectrum of 10
1.52.02.53.03.54.04.55.05.56.06.57.07.5f2 (ppm)
20
30
40
50
60
70
80
90
100
110
120
130
f1 (
ppm
)
Fig. S75. CD spectrum of 8. Concentration 857 g mL-1 . Fig. S74. CD spectrum of 5. Concentration 857 g mL-1 .Fig. S73. CD spectrum of 2. Concentration 857 g mL-1 .
Table S1. 1H and 13C NMR spectroscopic data for 4,9,10 in (CD3)2SO [H, multiplicity (J (Hz)); C, type]
4 9 10
Position H C H C H C
2 164.1, Cq 8.37, s 154.67, CH 8.52, s 155.63, CH
3 6.79, s 103.1, CH 122.85, Cq 121.99, Cq
4 182.6, Cq 180.88, Cq 182.59, Cq
4a 104.1, Cq 105.74, Cq 106.41, Cq
5 162.1, Cq 157.14, Cq 158.52, Cq
6 6.29, s 98.8, CH 105.26, Cq 113.66, Cq
7 161.6, Cq 159.72, Cq 165.61, Cq
8 106.5, Cq 6.47, s 94.94, CH 6.81, CH 91.24, CH
8a 154.9, Cq 157.95, Cq 153.93, Cq
1′ 122.0, Cq 121.49, Cq 121.58, Cq
2′,6′ 7.91, d, J = 8.5 128.8, CH 7.39, d, J = 8.4 130.64, CH 7.43, d, J = 8.4 130.74, CH
3′,5′ 6.95, d, J = 8.5 116.5, CH 6.84, d, J = 8.4 115.54, CH 6.85, d, J = 8.4 115.57, CH
4′ 159.5, Cq 156.30, Cq 157.93, Cq
1′′ 3.45, d, J = 6.3 21.8, CH2
2′′ 5.20, ca. t 122.9, CH 81.66, Cq 130.74, CH
3′′ 131.5, Cq 5.74, d, J = 9.8 126.69, CH 5.52, s 115.57, CH
4′′ 1.64, s or 1.77, s 18.3, CH3 or 25.9, CH3 6.69, d, J = 9.8 116.47, CH 67.90, Cq
5′′ 1.64, s or 1.77, s 3.49, dd, J = 11.9, 5.6; 3.50, dd, J = 11.9.5.6
67.50, CH2 1.54, s 29.25, CH3
6′′ 1.36, s 23.69, CH3 1.54, s 29.25, CH3
HO-5 12.81, s 13.36, s 13.74, s
HO-7 10.4, br or 10.8, br 5.13, t, J = 5.6
HO-4′ 10.4, br or 10.8, br 9.64, s 9.64, s
Table S2: Insulin secretion data
Glucose-stimulated insulin secretion by pure compounds. Miurine islets were incubated in KRB buffer containing 16.7 glucose
supplemented with or without pure compound (200 µM) / TB (200 µM) and secreted insulin was measured by ELISA. All data points
are an average of a minimum of n = 3 separate experiments and are expressed as means ± SEM. TB, (tolbutamide) was used as a
positive control.
Insulin secretion (ng islet-1 h-1)mean ± SEM
Compound No.
8.51 ± 0.38 Control38.51 ± 1.55 1
2.16 ± 0.95 2
32.86 ± 2.45 3
3.47 ± 0.36 4
35.23 ± 2.14 5
32.16 ± 0.69 6
12.08 ± 1.09 7
19.88 ± 0.53 8
25.85 ± 1.07 9
42.63 ± 1.48 10
19.49 ± 1.69 TB
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