supplementary material diterpenoid isosteviol synthesis … · 2019-06-20 · supplementary...
TRANSCRIPT
SUPPLEMENTARY MATERIAL
Synthesis and anticancer activities of glycosides and glycoconjugates of diterpenoid isosteviol
Radmila R. Sharipova,a* Mayya G. Belenok,a Bulat F. Garifullin,a Anastasiya S.
Sapunova,a Alexandra D. Voloshina,a Olga V. Andreeva,a Irina Yu. Strobykina,a Polina
V. Skvortsova,b Yuriy F. Zuev,b,c and Vladimir E. Kataeva
aArbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Arbuzov str., 8, Kazan, 420088, Russian Federation
bKazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center, Russian Academy of Sciences, Lobachevsky Str., 2/31, Kazan, 420111, Russian Federation
cKazan State Power Engineering University, 51, Krasnoselskaya str., Kazan, 420066, Russian Federation
*Corresponding author: Radmila R. Sharipova, e-mail: [email protected]
Electronic Supplementary Material (ESI) for MedChemComm.This journal is © The Royal Society of Chemistry 2019
1.1H NMR and 13C NMR Spectra of target compound 7
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.0
3.02
2.94
3.51
12.4
4
0.99
0.99
0.99
1.00
0.99
1.03
1.01
1.04
1.00
0.68
50
0.86
750.
9600
1.18
54
1.88
771.
9982
2.01
702.
0493
2.13
992.
1625
2.52
232.
5282
2.55
332.
5592
3.76
613.
7836
3.78
713.
7915
3.79
523.
8000
3.80
383.
8118
4.05
224.
0696
4.07
27
4.25
414.
2624
4.27
464.
2830
5.08
635.
1022
5.11
835.
1613
5.17
625.
1904
5.21
855.
2339
5.24
94
5.70
515.
7186
0102030405060708090100110120130140150160170180190200210220230
13.6
657
18.9
800
19.9
623
20.4
591
20.6
812
20.8
001
20.8
475
21.6
272
28.9
829
37.3
822
37.9
489
39.5
164
39.7
774
41.5
820
48.6
351
54.4
434
54.9
038
57.1
992
61.8
111
68.3
109
70.3
564
72.6
729
73.2
062
76.9
483
77.1
604
77.3
723
91.3
511
169.
1946
169.
5213
170.
1884
170.
6051
175.
5794
222.
1086
2.1H NMR and 13C NMR Spectra of target compound 8
1.01.52.02.53.03.54.04.55.05.5
2.78
2.83
3.36
9.32
2.88
1.01
0.99
2.31
1.01
1.06
0.98
1.00
0.69
15
0.81
22
0.96
67
1.19
29
1.91
741.
9806
2.01
442.
0262
2.17
01
2.53
032.
5386
2.57
712.
5847
3.99
444.
0117
4.02
804.
1015
4.11
88
5.05
205.
0607
5.07
795.
0865
5.31
515.
3402
5.36
195.
4039
5.40
92
5.67
365.
6944
0102030405060708090100110120130140150160170180190200210220
13.6
924
19.0
434
19.9
636
20.4
512
20.6
237
20.7
321
20.7
989
20.9
567
21.5
877
29.0
598
37.3
853
37.9
149
38.2
505
39.5
190
39.7
771
41.5
837
44.2
272
48.6
461
48.7
991
54.4
563
54.8
970
57.2
451
60.9
321
66.9
184
67.8
913
71.2
389
71.6
591
77.1
604
91.7
856
169.
3533
170.
0322
170.
3270
170.
3856
175.
6385
222.
1870
3.1H NMR and 13C NMR Spectra of target compound 9
0.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2
2.69
2.70
2.58
3.14
6.13
3.24
1.27
1.13
1.19
1.12
1.18
3.18
1.00
0.76
240.
8042
0.97
88
1.28
10
1.98
841.
9972
2.07
132.
0906
2.17
142.
1988
2.23
25
2.60
012.
6096
2.64
702.
6560
4.00
174.
0560
4.07
174.
0780
4.10
254.
1085
4.26
124.
2754
4.29
174.
3060
5.22
34
5.35
52
6.08
336.
0879
0102030405060708090100110120130140150160170180190200210220230240
13.6
379
18.7
957
19.7
935
20.3
399
20.5
283
20.6
487
20.7
031
21.8
181
28.8
989
37.2
033
38.1
098
39.4
365
41.4
429
44.3
189
48.2
721
48.6
641
54.2
011
54.6
329
56.8
717
62.5
038
65.4
996
68.1
593
69.0
074
71.6
209
90.7
892
169.
4797
169.
5982
169.
9296
170.
4549
174.
3780
221.
8357
4.1H NMR and 13C NMR Spectra of target compound 11
0.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.0
3.16
2.75
2.80
8.48
1.02
0.99
3.37
1.16
1.21
0.97
1.20
1.00
0.68
940.
8424
0.96
20
1.20
42
1.90
812.
0185
2.02
532.
1415
2.16
38
2.52
892.
5347
2.55
992.
5657
3.71
84
4.12
174.
1379
5.17
935.
1935
5.20
745.
2269
5.24
275.
2586
5.27
845.
2935
5.30
88
5.75
665.
7699
0102030405060708090100110120130140150160170180190200210220230
13.6
260
18.9
685
19.9
655
20.4
615
20.5
828
20.6
900
20.8
339
21.6
533
28.9
629
37.3
949
37.9
666
39.5
189
39.7
652
41.5
708
48.6
388
52.9
839
54.4
413
54.9
005
57.2
272
69.2
716
70.2
501
72.4
497
72.9
564
76.9
478
77.1
598
91.1
667
166.
8158
169.
1039
169.
4815
170.
0398
175.
5248
222.
1696
5.1H NMR and 13C NMR Spectra of target compound 12
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.92
3.10
3.36
1.19
1.10
4.13
2.14
1.00
0.77
750.
8228
0.95
83
1.18
351.
2378
1.42
13
1.68
071.
8154
1.86
301.
9112
2.17
532.
2101
2.64
092.
6493
2.68
652.
6952
3.49
523.
5132
3.58
533.
6047
3.62
643.
8074
3.81
693.
8513
3.87
31
5.47
885.
4988
0102030405060708090100110120130140150160170180190200210220230
14.1
176
19.9
629
20.2
075
21.4
703
22.7
400
29.0
588
39.3
223
40.7
709
45.0
623
49.0
005
49.2
138
49.4
265
49.4
708
49.6
394
49.8
499
55.8
294
58.6
283
71.1
291
74.0
486
78.6
774
78.7
053
95.6
183
178.
0657
225.
2688
6.1H NMR and 13C NMR Spectra of target compound 13
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.6
2.62
2.69
2.90
0.99
0.99
1.21
0.99
3.22
0.96
1.00
0.71
920.
7910
0.89
92
1.17
75
1.85
56
2.11
282.
1466
2.55
412.
5624
2.60
072.
6093
3.13
313.
3965
3.41
403.
4315
3.44
963.
4593
3.47
473.
5335
3.54
713.
5626
3.63
443.
7427
3.75
723.
8795
3.88
76
5.28
245.
3029
0102030405060708090100110120130140150160170180190200210220230
14.1
369
19.9
866
20.1
936
21.4
773
22.7
697
29.0
961
38.5
227
39.3
278
40.7
780
42.5
456
45.0
887
49.4
254
49.5
053
49.8
567
55.1
931
55.8
508
70.0
954
71.3
351
75.4
858
77.3
781
96.1
327
178.
1458
225.
2534
7.1H NMR and 13C NMR Spectra of target compound 14
1.01.52.02.53.03.54.04.55.05.56.0
3.01
3.41
3.27
1.05
1.06
0.97
1.04
4.09
1.00
0.74
59
0.94
151.
0314
1.21
45
1.94
27
2.14
712.
1708
2.58
052.
5866
2.61
182.
6179
3.30
95
3.57
07
3.83
25
4.58
58
6.02
54
0102030405060708090100110120130140150160170180190200210220230
13.9
673
19.5
771
20.0
106
20.9
669
22.4
613
29.1
915
37.9
339
38.3
570
38.7
551
40.2
143
40.3
128
41.8
876
44.9
162
49.4
609
54.7
087
55.1
810
57.5
754
62.0
739
67.2
430
70.3
832
72.1
236
76.9
420
78.0
819
78.2
969
95.0
499
176.
5281
224.
7992
8.1H NMR and 13C NMR Spectra of target compound 15
0.40.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.80
3.22
2.52
8.20
3.76
1.05
1.13
1.27
1.38
1.41
1.19
2.37
1.00
1.07
0.69
300.
7324
0.96
78
1.18
47
1.93
142.
0310
2.03
562.
0401
2.06
352.
1914
2.22
32
2.53
552.
5524
2.57
962.
5993
3.72
033.
7953
4.04
214.
1468
4.23
694.
2499
4.26
774.
2803
4.31
724.
4045
5.04
06
5.15
13
5.45
145.
4759
5.62
655.
6486
102030405060708090100110120130140150160170180190200210220
13.6
624
19.9
691
20.4
608
20.7
083
20.7
538
20.8
272
23.4
210
29.0
526
37.4
066
38.2
590
39.5
373
39.7
648
44.2
414
48.6
942
48.8
062
54.4
372
54.8
657
57.2
756
62.0
009
68.2
495
72.8
602
73.1
495
92.1
616
169.
3881
169.
8620
170.
6991
171.
3700
176.
1699
222.
3698
9.1H NMR and 13C NMR Spectra of target compound 16
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.97
3.10
3.16
3.10
1.06
1.04
1.04
1.12
1.04
1.06
0.98
1.04
1.00
0.75
99
0.94
27
1.20
33
1.98
09
2.15
122.
1843
2.55
162.
5606
2.59
802.
6071
3.30
973.
3485
3.35
903.
3935
3.41
513.
4384
3.45
293.
4776
3.49
923.
6830
3.69
533.
7131
3.72
543.
8115
3.81
703.
8416
3.84
733.
8671
3.88
993.
9140
4.80
14
5.59
155.
6138
-100102030405060708090100110120130140150160170180190200210220
14.2
469
20.0
013
20.1
494
21.4
318
22.7
625
23.3
677
29.2
731
38.4
292
39.2
297
40.6
481
40.8
210
45.1
537
49.7
779
49.8
224
55.8
611
55.9
208
58.2
491
62.4
532
71.5
668
76.3
517
78.7
471
93.8
403
173.
3085
177.
7493
10.1H NMR and 13C NMR Spectra of target compound 20
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.89
3.01
3.65
9.01
3.45
1.97
1.02
5.47
1.04
1.06
0.97
1.00
0.70
320.
8340
0.97
50
1.18
50
1.93
571.
9906
2.02
682.
0372
2.16
192.
3656
2.37
672.
3846
2.59
672.
6058
2.64
302.
6524
3.95
77
4.16
714.
1850
5.06
925.
0778
5.09
535.
1039
5.30
245.
3232
5.32
845.
4228
5.43
05
5.70
685.
7275
0102030405060708090100110120130140150160170180190200210220
13.5
269
19.9
608
20.4
578
20.6
176
20.7
093
20.7
307
21.8
522
24.2
131
25.6
900
28.2
785
29.0
913
33.9
633
37.4
366
38.1
521
39.5
846
41.6
575
43.9
605
48.5
493
48.8
118
54.4
309
54.8
572
57.2
187
61.0
815
63.9
436
68.0
466
70.9
246
71.8
264
76.8
420
77.1
600
77.4
779
92.2
297
169.
3770
170.
0069
170.
1960
170.
3863
171.
4861
177.
3766
222.
4041
11.1H NMR and 13C NMR Spectra of target compound 21
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.92
2.99
2.49
8.57
2.75
1.96
1.00
3.21
2.19
1.00
1.02
0.98
1.00
0.70
38
0.86
42
0.96
93
1.18
07
1.92
211.
9857
2.02
012.
0313
2.15
61
2.33
262.
3831
2.60
202.
6073
2.63
332.
6392
3.94
74
4.13
974.
1513
4.17
03
5.06
735.
0729
5.08
465.
0903
5.30
905.
3230
5.34
025.
4166
5.42
21
5.69
785.
7116
0102030405060708090100110120130140150160170180190200210220230
19.1
428
20.4
963
20.7
442
21.8
934
24.6
643
26.2
714
28.6
298
29.0
673
29.1
106
29.2
445
29.2
748
29.4
337
34.1
792
37.4
909
38.1
369
38.1
968
39.6
289
40.0
489
41.7
300
43.9
934
48.5
994
54.4
853
54.8
994
57.2
827
61.1
204
64.4
142
66.9
807
68.0
591
71.0
092
71.8
576
92.2
060
169.
3813
170.
0498
170.
2264
170.
4121
171.
8829
177.
4788
222.
4365
12.1H NMR and 13C NMR Spectra of target compound 22
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2
3.25
3.12
3.43
1.95
1.00
4.33
1.22
1.09
1.95
1.00
0.70
660.
8503
0.96
94
1.18
88
1.92
741.
9997
2.05
192.
0849
2.17
402.
4081
2.42
692.
4453
2.59
212.
6015
2.63
872.
6477
3.96
104.
1320
4.25
904.
2713
4.28
984.
3020
5.23
195.
2580
5.31
075.
3507
6.09
696.
1016
-100102030405060708090100110120130140150160170180190200210220230
18.9
870
20.3
287
20.6
066
20.6
902
20.7
492
21.7
401
24.2
126
25.6
537
28.1
996
28.9
863
33.8
240
37.3
295
37.9
548
38.0
354
39.4
669
39.8
528
41.5
271
43.8
458
48.4
296
48.6
845
54.3
040
54.7
476
57.1
098
62.1
363
63.8
536
65.5
742
68.3
391
68.7
986
70.6
392
90.5
697
169.
4959
169.
6827
169.
9259
170.
4801
170.
5508
177.
2734
222.
2937
13.1H NMR and 13C NMR Spectra of target compound 23
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.86.06.2
2.97
3.24
3.51
3.05
1.97
1.10
3.92
1.21
1.03
1.83
1.00
0.70
540.
7879
0.96
81
1.18
20
1.94
371.
9980
2.04
812.
0808
2.16
322.
3832
2.40
222.
4207
2.59
452.
6036
2.64
062.
6498
3.95
394.
1132
4.25
094.
2634
4.28
174.
2943
5.25
045.
3132
5.36
33
6.08
856.
0926
0102030405060708090100110120130140150160170180190200210220
13.3
955
18.9
797
19.8
364
20.3
330
20.5
897
20.6
226
20.6
577
20.7
279
21.7
320
24.6
174
26.1
236
28.4
732
28.9
562
29.1
230
29.2
821
34.0
024
37.3
277
38.0
343
39.4
678
39.8
862
41.5
623
43.8
310
48.4
376
48.6
902
54.3
149
54.7
320
57.1
149
65.6
043
68.4
042
90.4
494
169.
4887
169.
6821
169.
9005
170.
5462
170.
8146
177.
3378
222.
3257
14.1H NMR and 13C NMR Spectra of target compound 26
0.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.85
3.57
2.49
1.04
1.86
1.25
1.08
2.41
1.06
2.25
2.10
1.14
1.00
0.68
760.
7754
0.95
84
1.16
75
1.88
891.
9543
2.01
782.
0241
2.06
582.
1387
2.17
362.
3008
2.42
522.
5774
2.58
572.
6238
2.63
22
3.77
073.
8340
3.94
494.
0450
4.06
954.
1319
4.18
744.
2921
5.05
49
5.20
78
5.71
395.
7357
5.85
445.
8780
102030405060708090100110120130140150160170180190200210220
13.5
398
19.0
816
19.9
578
20.4
672
20.6
796
20.7
370
20.8
160
23.2
425
24.1
293
25.6
864
28.2
543
29.0
723
37.4
270
38.1
512
39.6
003
41.6
403
43.9
738
48.5
556
48.8
648
54.4
141
54.8
111
57.1
880
63.9
421
72.9
892
76.8
424
77.1
601
77.4
780
92.6
149
169.
3782
170.
1805
170.
7468
171.
2038
172.
0372
177.
4908
222.
7442
15.1H NMR and 13C NMR Spectra of target compound 27
0.60.81.01.21.41.61.82.02.22.42.62.83.03.23.43.63.84.04.24.44.64.85.05.25.45.65.8
2.60
2.71
2.93
2.87
5.57
2.97
1.12
1.93
1.00
0.90
2.02
0.86
1.89
1.81
1.78
0.70
48
0.97
18
1.17
78
1.87
121.
9031
2.02
452.
0291
2.07
422.
1577
2.19
042.
3337
2.35
272.
3712
2.58
792.
5972
2.63
452.
6436
3.74
933.
8225
3.94
294.
0554
4.09
444.
0999
4.12
544.
1307
4.21
774.
3355
5.09
805.
1219
5.13
315.
1466
5.16
99
5.68
075.
7027
5.71
925.
7432
102030405060708090100110120130140150160170180190200210220230
13.5
651
19.1
454
20.0
108
20.4
925
20.7
102
20.7
599
21.9
102
24.6
629
26.2
625
28.5
795
29.0
112
29.1
348
29.1
847
29.2
160
29.3
964
34.1
860
37.5
188
38.1
539
40.0
588
41.7
261
48.6
222
53.2
105
54.4
755
54.8
858
57.2
827
64.4
076
72.8
621
73.1
318
92.6
447
169.
3524
170.
0435
170.
7663
171.
2406
172.
4494
177.
5461
222.
7119