S. Luan et al.
Bioorganic Chemistry 109 (2021) 104699
(octanoic acid, myristic acid, palmitic acid, stearic acid, oleic acid and
linoleic acid) (0.3 mmol), reacted at 110 ℃ under vacuum for 10 to 20
min. The residue was purified by flash chromatography on silica gel
(eluting by petroleum ether-acetone, 15:1 to 4:1) to give the product
18–22, respectively.
3.47 (d, J = 8.8 Hz, 1H, H-18β), 3.35 (d, J = 5.3 Hz, 1H, H-16α), 3.30 (s,
3H, 18′–OCH3), 3.27 (s, 3H, 1′–OCH3), 3.16 (s, 3H, 6′–OCH3), 1.10 (t, J
= 7.1 Hz, 3H, N-CH2CH3), 0.93 – 0.84 (m, 3H, H-18′′′). The 13C NMR
data are listed in Table S2. HRMS calculated for C50H78NO11 868.5575,
found 868.5588[M + H]+.
4.1.9. 8-capryloyl-aconitine (18). Orange oil, yield 52.20%. IR (KBr)
3456, 2924, 1639, 1383, 1274, 1094, 749, 709 cmꢀ 1; 1H NMR (400
MHz, CDCl3) δ 8.02 (d, J = 7.3 Hz, 1H, H-2′′, 6′′), 7.55 (t, J = 7.4 Hz, 1H,
H-4′′), 7.43 (t, J = 7.7 Hz, 2H, H-3′′, 5′′), 4.85 (d, J = 4.9 Hz, 1H, H-14β),
4.48 (d, J = 2.6 Hz, 1H, H-15β), 4.43 (dd, J = 5.3, 2.6 Hz, 1H, H-3β),
4.02 (d, J = 6.3 Hz, 1H, H-6β), 3.94 (s, 1H, H-17), 3.75 (s, 3H,
4.1.14. General procedure for the preparation of 3-acetyl-8-lipo diterpenoid
alkaloid (23)
Aconitine linoleate (11) (86.5 mg, 0.1 mmol) was mixed with Ac2O
(0.12 mmoL) in pyridine, reacted at room temperature for 10 h. The
residue was purified by flash chromatography on silica gel (eluting by
petroleum ether-acetone, 15:1 to 4:1) to give the product 23.
16′–OCH3), 3.60 (d, J = 8.9 Hz, 1H, H-18
α), 3.45 (d, J = 8.9 Hz, 1H, H-
18β), 3.33 (d, J = 5.4 Hz, 1H, H-16
α
), 3.28 (s, 3H, 18′–OCH3), 3.25 (s,
4.1.15. 3-acetyl-8-linoleate-aconitine (23). Light yellow oil, yield 52.07%.
IR (KBr)
3H, 1′–OCH3), 3.14 (s, 3H, 6′–OCH3), 1.08 (t, J = 7.0 Hz, 3H, N-
CH2CH3), 0.87 (t, J = 6.6 Hz, 3H, H-8′′′). The 13C NMR data are listed in
Table S2. HRMS calculated for C40H60NO11 730.4166, found 730.4166
[M + H]+.
3452, 2922, 2855, 1638, 1384, 1276, 1095, 749 cmꢀ 1; 1H NMR (400
MHz, CDCl3) δ 8.02 (d, J = 7.1 Hz, 2H, H-2′′, 6′′), 7.55 (t, J = 7.4 Hz, 1H,
H-4′′), 7.44 (t, J = 7.7 Hz, 2H, H-3′′, 5′′), 5.43 – 5.26 (m, 4H, 9′′′, 10′′′,
12′′′, 13′′′), 4.91 (dd, J = 12.7, 5.6 Hz, 1H, H-3), 4.85 (d, J = 5.0 Hz, 1H,
H-14β), 4.46 (d, J = 2.5 Hz, 1H, OH-15), 4.42 (dd, J = 5.4, 2.8 Hz, 1H, H-
15β), 4.06 (d, J = 7.0 Hz, 1H, H-6β), 3.88 (s, 1H, OH-13), 3.77 (d, J =
4.1.10. 8-myristoyl-aconitine (19). Light yellow oil, yield 59.89%. IR
(KBr)
3492, 2925, 2854, 1719, 1452, 1382, 1277, 1190, 1099, 1030, 984,
919, 710, 601 cmꢀ 1; 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.2 Hz,
1H, H-2′′, 6′′), 7.55 (t, J = 7.4 Hz, 1H, H-4′′), 7.43 (t, J = 7.6 Hz, 2H, H-
3′′, 5′′), 4.84 (d, J = 4.9 Hz, 1H, H-14β), 4.47 (d, J = 2.6 Hz, 1H, H-15β),
4.42 (dd, J = 5.2, 2.5 Hz, 1H, H-3β), 4.01 (d, J = 6.4 Hz, 1H, H-6β), 3.94
(s, 1H, H-17), 3.74 (s, 3H, 16′–OCH3), 3.59 (d, J = 8.9 Hz, 1H, 1H, H-
8.9 Hz, 1H, H-18
16
α
) 3.74 (s, 3H, 16′-OCH3), 3.31 (d, J = 5.3 Hz, 1H, H-
α
), 3.25 (s, 3H, 18′–OCH3), 3.19 (s, 3H, 1′–OCH3), 3.18 (s, 3H,
6′–OCH3), 2.06 (s, 3H, 3′–COCH3), 1.10 (t, J = 7.1 Hz, 3H, N-CH2CH3),
0.90 (t, 3H, H-18′′′). The 13C NMR data are listed in Table S1. HRMS
calculated for C52H78NO12 908.5524, found 908.5525[M + H]+.
18
α
), 3.44 (d, J = 8.8 Hz, 1H, H-18β), 3.32 (d, J = 5.4 Hz, 1H, H-16
α
),
4.1.16. General procedure for the preparation of fluoro-substituted 8-lipo
diterpenoid alkaloids (24–25)
3.28 (s, 3H, 18′–OCH3), 3.24 (s, 3H, 1′–OCH3), 3.14 (s, 3H, 6′–OCH3),
1.08 (t, J = 7.1 Hz, 3H, N-CH2CH3), 0.87 (t, J = 6.7 Hz, 3H, H-14′′′). The
13C NMR data are listed in Table S2. HRMS calculated for C46H72NO11
814.5105, found 814.5108[M + H]+.
C-18 unsaturated fatty acid (oleic acid, linoleic acid) (0.5 mmol)
mixed with Olah agent (5 mmol), and reacted at 0 ◦C for 180 min. The
reaction was terminated by ice water, then extracted by diethyl ether.
After the solvent was removed under reduced pressure, the residue was
purified by flash chromatography on silica gel to give the fluoro-fatty
acid. Aconitine (4) (64.5 mg, 0.1 mmol) was mixed with different
fluoro-fatty acid (0.3 mmol), reacted at 110 ℃ under vacuum for 20 to
30 min. The residue was purified by flash chromatography on silica gel
(eluting by petroleum ether-acetone, 15:1 to 4:1) to give the product
24–25, respectively.
4.1.11. 8-palmityl-aconitine (20). Orange oil, yield 59.82%. IR (KBr)
3473, 2924, 2853, 1718, 1452, 1383, 1277, 1189, 1097, 1030, 984,
709, 601 cmꢀ 1; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.3 Hz, 1H, H-
2′′, 6′′), 7.55 (t, J = 7.4 Hz, 1H, H-4′′), 7.43 (t, J = 7.7 Hz, 2H, H-3′′, 5′′),
4.85 (d, J = 4.9 Hz, 1H, H-14β), 4.48 (d, J = 2.6 Hz, 1H, H-15β), 4.43
(dd, J = 5.3, 2.6 Hz, 1H, H-3β), 4.02 (d, J = 6.3 Hz, 1H, H-6β), 3.94 (s,
1H, H-17), 3.75 (s, 3H, 16′–OCH3), 3.60 (d, J = 8.9 Hz, 1H, H-18
α), 3.45
(d, J = 8.9 Hz, 1H, H-18β), 3.33 (d, J = 5.4 Hz, 1H, H-16
α), 3.28 (s, 3H,
4.1.17. 8-(9,13-difluorooctadecanoyl)oxy)-aconitine (24)
18′–OCH3), 3.25 (s, 3H, 1′–OCH3), 3.14 (s, 3H, 6′–OCH3), 1.08 (t, J =
7.0 Hz, 3H, N-CH2CH3), 0.87 (t, J = 6.6 Hz, 3H, H-16′′′). The 13C NMR
data are listed in Table S2. HRMS calculated for C48H76NO11 842.5418,
found 842.5430[M + H]+.
White solid, yield 12.14%. IR (KBr): 3549, 2926, 2855, 1714, 1636,
1453, 1384, 1277, 1098, 710 cmꢀ 1; 1H NMR (400 MHz, CDCl3) δ 8.02
(d, J = 7.3 Hz, 2H, H-2′′, 6′′), 7.56 (t, J = 7.4 Hz, 1H, H-4′′), 7.44 (t, J =
7.6 Hz, 2H, H-3′′, 5′′), 4.85 (d, J = 4.9 Hz, 1H, H-14β), 4.48 (dd, J = 2.9,
1.2 Hz, 1H, OH-15), 4.43 (dd, J = 5.5, 2.7 Hz, 1H, H-15β), 4.02 (dd, J =
6.5, 1.8 Hz, 1H, H-6β), 3.94 (s, 1H, OH-13), 3.75 (s, 3H, 16′–OCH3), 3.60
4.1.12. 8-stearatyl-aconitine (21). Orange oil, yield 52.82%. IR (KBr)
3452, 2918, 2850, 1635, 1384, 1094, 708 cmꢀ 1; 1H NMR (400 MHz,
CDCl3) δ 8.02 (d, J = 7.2 Hz, 1H, H-2′′, 6′′), 7.56 (t, J = 7.4 Hz, 1H, H-
4′′), 7.44 (t, J = 7.7 Hz, 2H, H-3′′, 5′′), 4.86 (d, J = 5.0 Hz, 1H, H-14β),
4.49 (d, J = 2.6 Hz, 1H, H-15β), 4.44 (dd, J = 5.3, 2.4 Hz, 1H, H-3β),
4.03 (d, J = 6.3 Hz, 1H, H-6β), 3.96 (s, 1H, H-17), 3.76 (s, 3H,
and 3.45 (d, J = 8.9 Hz, each 1H, H-18), 3.33 (d, J = 5.4 Hz, 1H, H-16α),
3.29 (s, 3H, 18′–OCH3), 3.25 (s, 3H,1′–OCH3), 3.15 (s, 3H, 6′–OCH3),
1.09 (t, J = 7.1 Hz, 3H, N-CH2CH3), 0.88 (t, J = 6.4 Hz, 3H, H-18′′′). The
13C NMR data are listed in Table S3. HRMS calculated for C50H78F2NO11
906.5543, found 906.5534 [M + H]+.
16′–OCH3), 3.60 (d, J = 8.8 Hz, 1H, H-18
α), 3.45 (d, J = 8.9 Hz, 1H, H-
18β), 3.34 (d, J = 5.4 Hz, 1H, H-16
α
), 3.29 (s, 3H, 18′–OCH3), 3.26 (s,
4.1.18. 8-(10-fluorooctadecanoyl)oxy)-aconitine (25)
3H, 1′–OCH3), 3.15 (s, 3H, 6′–OCH3), 1.10 (t, J = 7.1 Hz, 3H, N-
CH2CH3), 0.87 (t, J = 6.8 Hz, 3H, H-18′′′). The 13C NMR data are listed in
Table S2. HRMS calculated for C50H80NO11 870.5731, found 870.5759
[M + H]+.
White solid, yield 38.26%. IR (KBr): 3490, 2926, 2855, 1721, 1452,
1382, 1277, 1099, 1030, 984, 710 cmꢀ 1; 1H NMR (400 MHz, CDCl3) δ
8.01 (d, J = 8.2 Hz, 2H, H-2′′, 6′′), 7.55 (t, J = 7.4 Hz, 1H, H-4′′), 7.43 (t,
J = 7.6 Hz, 2H, H-3′′, 5′′), 4.84 (d, J = 4.9 Hz, 1H, H-14β), 4.47 (d, J =
2.9 Hz, 1H, OH-15), 4.42 (dd, J = 5.6, 2.5 Hz, 1H, H-15β), 4.01 (d, J =
6.6 Hz, 1H, H-6β), 3.94 (s, 1H, OH-13), 3.74 (d, J = 1.6 Hz, 3H,
16′–OCH3), 3.59 and 3.44 (d, J = 8.9 Hz, each 1H, H-18), 3.32 (d, J =
4.1.13. 8-oleoyl-aconitine (22). Light yellow oil, yield 55.22%. IR (KBr)
3451, 2924, 2851, 1636, 1384, 693, 620 cmꢀ 1; 1H NMR (400 MHz,
CDCl3) δ 8.04 (d, J = 7.2 Hz, 1H, H-2′′, 6′′), 7.57 (t, J = 7.4 Hz, 1H, H-
4′′), 7.45 (t, J = 7.6 Hz, 2H, H-3′′, 5′′), 5.46 – 5.29 (m, 2H, 9′′′, 10′′′),
4.87 (d, J = 4.9 Hz, 1H, H-14β), 4.49 (d, J = 2.4 Hz, 1H, H-15β), 4.45
(dd, J = 5.2, 2.5 Hz, 1H, H-3β), 4.04 (d, J = 6.4 Hz, 1H, H-6β), 3.96 (s,
5.5 Hz, 1H, H-16
α
), 3.28 (d, J = 1.5 Hz, 3H, 18′–OCH3), 3.24 (d, J = 1.6
Hz, 3H, 1′–OCH3), 3.14 (d, J = 1.4 Hz, 3H, 6′–OCH3), 1.08 (t, J = 7.0 Hz,
3H, N-CH2CH3), 0.86 (t, J = 6.6 Hz, 3H, H-18′′′). The 13C NMR data are
listed in Table S3. HRMS calculated for C50H79FNO11 888.5637, found
888.5640 [M + H]+.
1H, OH-13), 3.77 (s, 3H, 16′–OCH3), 3.62 (d, J = 8.9 Hz, 1H, H-18
α),
6