Arch. Pharm. Chem. Life Sci. 2017, 350, e1700178
Synthesis and Bioevaluation of a-Amyrin, b-Amyrin, and Lupeol
ARC HH PHARM
Archiv der Pharmazie
ꢀ
1
ꢀ1
(
85% yield). [a]
D
¼ þ74.37 (c ¼ 0.135, CHCl
3
). FT-IR n (cm ):
(97% yield). [a]
D
¼ þ83.1 (c ¼ 0.22, CHCl
3
). FT-IR n (cm ): 3295,
3
1
5
2
3
378, 2947, 2869, 2363, 2335, 1637, 1464, 1385, 1375, 1362,
2947, 2869, 2853, 1639, 1464, 1385, 1360, 1190, 1035, 996, 951,
1
1
343, 1095, 1076, 1045, 1004, 658. H NMR (CDCl
3
, 300 MHz) d
814, 659. H NMR (CDCl
3
, 500 MHz) d 5.19 (t, J ¼ 2.1 Hz, 1H),
.19(t,J ¼ 3.6 Hz,1H),3.53(d,J ¼ 11.0 Hz,1H),3.18–3.08(m,2H),
3.22 (dd, J ¼ 2.9, 6.8 Hz, 1H), 2.03–0.73 (m, 23H), 1.14 (s, 3H),
.03–0.75 (m, 23H), 1.19 (s, 3H), 1.00 (s, 3H), 0.98 (s, 3H), 0.97 (s,
1.00 (s, 3H), 0.97 (s, 3H), 0.94 (s, 3H), 0.87 (s, 6H), 0.83 (s, 3H),
þ
13
H), 0.89 (s, 3H), 0.79 (s, 6H). MS (ESI) m/z: 465.37 [MþNa] .
3
0.79 (s, 3H). C NMR (CDCl , 125 MHz) d 145.2, 121.8, 79.0,
5.2, 47.7, 47.3, 46.9, 41.8, 39.8, 38.8, 38.6, 37.2, 37.0, 34.8,
5
3
-Acetylerythrodiol (12)
33.3, 32.7, 32.5, 31.1, 28.4, 28.1, 27.3, 27.0, 26.2, 26.0, 23.7,
According to the procedure for preparation of 8, 12 was
prepared from 11 as a white solid (72% yield for two steps).
23.5, 18.4, 16.8, 15.6, 15.5. ESI-HRMS calcd. for C30
([MþNa] ): 449.3758; found: 449.3770.
H
50ONa
þ
ꢀ
1
[
2
(
3
2
3
1
3
2
a]
873, 1709, 1464, 1370, 1268, 1050, 1029, 1008, 735. H NMR
CDCl
D
¼ þ68.39 (c ¼ 0.753, CHCl
3
). FT-IR n (cm ): 3490, 2945,
1
3-Acetylbetulin (15)
According to the procedure for preparation of 8, 15 was
3
, 300 MHz) d 5.19 (t, J ¼ 3.5 Hz, 1H), 4.52–4.47 (m, 1H),
.54 (d, J ¼ 11.0 Hz, 1H), 3.20 (d, J ¼ 11.0 Hz, 1H), 2.04 (s, 3H),
.01–0.82 (m, 23H), 1.16 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H), 0.89 (s,
prepared from betulin (6) as a white solid (57% yield for two
ꢀ
1
steps). FT-IR n (cm ): 3416, 2944, 2872, 1732, 1642, 1453, 1384,
13
1
H), 0.87 (s, 6H), 0.86 (s, 3H). C NMR (CDCl
3
, 75 MHz) d 171.0,
44.2, 122.3, 80.9, 69.7, 55.2, 47.5, 46.4, 42.3, 41.7, 39.8, 38.3,
7.7, 36.9, 36.8, 34.1, 33.2, 32.5, 31.0, 30.9, 28.0, 25.8, 25.5,
3
1374, 1247, 1027, 979, 887, 750. H NMR (CDCl , 300 MHz) d
4.68 (s, 1H), 4.59 (s, 1H), 4.50–4.45 (m, 1H), 3.80 (d, J ¼ 11.0 Hz,
1H), 3.34 (d, J ¼ 10.8 Hz, 1H), 2.43–2.34 (m, 1H), 2.04 (s, 3H),
2.00–0.78 (m, 24H), 1.69 (s, 3H), 1.03 (s, 3H), 0.98 (s, 3H), 0.85 (s,
3.5, 22.0, 21.3, 18.2, 16.7, 16.6, 15.6. MS (ESI) m/z: 507.37
þ
þ
[
MþNa] .
6H), 0.84 (s, 3H). MS (ESI) m/z: 507.36 [MþNa] .
3
-Acetyloleanolic aldehyde (13)
3-Acetylbetulinic aldehyde (16)
According to the procedure for preparation of 9, 13 was
According to the procedure for preparation of 9, 16 was
prepared from 12 as a white amorphous solid (84% yield).
prepared from 15 as a white amorphous solid (90% yield). FT-
ꢀ
1
ꢀ1
[
a]
D
¼ þ63.5 (c ¼ 0.532, CHCl
3
). FT-IR n (cm ): 3441, 2948,
IR n (cm ): 3438, 2941, 2865, 1727, 1641, 1447, 1377, 1245,
1
2
1
5
2
709, 2361, 2339, 1729, 1465, 1439, 1375, 1362, 1249, 1148,
026, 991, 928, 653. H NMR (CDCl
1029, 979, 884. H NMR (CDCl
3
, 500 MHz) d 9.68 (s, 1H), 4.76 (s,
1
3
, 500 MHz) d 9.40 (s, 1H),
1H), 4.63 (s, 1H), 4.47 (dd, J ¼ 5.8, 10.6 Hz, 1H), 2.89–2.83 (m,
1H), 2.09–0.77 (m, 24H), 2.04 (s, 3H), 1.70 (s, 3H), 0.97 (s, 3H),
0.92 (s, 3H), 0.85 (s, 3H), 0.84 (s, 3H), 0.83 (s, 3H). MS (ESI) m/z:
.34 (t, J ¼ 2.0 Hz, 1H), 4.51–4.47 (m, 1H), 2.64–2.61 (m, 1H),
.04 (s, 3H), 2.01–1.95 (m, 1H), 1.90–1.87 (m, 2H), 1.71–0.82
þ
(
m, 19H), 1.14 (s, 3H), 0.93 (s, 3H), 0.92 (s, 3H), 0.91 (s, 3H),
.87 (s, 3H), 0.85 (s, 3H), 0.74 (s, 3H). C NMR (CDCl ,
3
25 MHz) d 207.3, 170.9, 143.0, 123.1, 80.8, 55.3, 49.0, 47.5,
5.6, 41.7, 40.4, 39.6, 38.2, 37.7, 36.9, 33.1, 33.0, 32.7, 30.6,
505.36 [MþNa] .
1
3
0
1
4
2
1
2-(3b-Acetoxy-28-norlup-20(29)-en-17-yl)-1,3-dithiolane
(17)
A solution of Me Al (8.1 mL, 2.0 M in toluene) in CH Cl
3 2 2
(16 mL) was cooled to ꢀ78°C, and treated slowly with 1,2-
ethanedithiol (0.68 mL). After 5 min of stirring at ꢀ78°C, the
resultant white slurry was warmed to 0°C and stirred for an
additional 30 min. Upon completion, the reaction contents
8.0, 27.7, 26.7, 25.5, 23.5, 23.4, 22.1, 21.2, 18.2, 17.0, 16.6,
þ
5.4. ESI-HRMS calcd. for C32
H
50
O
3
Na ([MþNa] ): 505.36522;
found: 505.36546.
2
-(3b-Acetoxy-28-norolean-12-en-17-yl)-1,3-dithiolane
(
14)
2 2 2 2
were concentrated to afford Me AlSCH CH SAlMe (1.66 g,
According to the procedure for preparation of 10, 14 was
8.1 mmol) as a white free flowing powder. A solution of 6
prepared from 13 as a white amorphous solid (80% yield).
(1.3 g, 2.7 mmol) in 1,2-dichloroethane (30 mL) was added
ꢀ
1
[
a]
D
¼ þ45 (c ¼ 0.12, CHCl
3
). FT-IR n (cm ): 2947, 2922, 2853,
slowly to
a
solution of Me
2
AlSCH
2
CH
2
SAlMe
2
(1.66 g,
2
360, 2334, 1734, 1657, 1555, 1275, 1260, 1049, 764, 751.
H NMR (CDCl
.52–4.47 (m, 1H), 3.22–3.08 (m, 4H), 2.05 (s, 3H), 2.00–0.83 (m,
3H), 1.16 (s, 3H), 0.98 (s, 3H), 0.96 (s, 3H), 0.93 (s, 3H), 0.89 (s,
H), 0.88 (s, 3H), 0.87 (s, 3H). C NMR (CDCl , 75 MHz) d 171.0,
3
43.5, 123.2, 80.9, 62.0, 55.3, 47.5, 46.9, 46.7, 41.6, 40.6, 39.8,
9.0, 38.8, 38.3, 37.7, 36.8, 34.2, 33.0, 32.3, 31.1, 28.0, 26.2,
8.1 mmol) in 1,2-dichloroethane (30 mL) at room temperature.
After stirring for overnight, the reaction content was
quenched by the slow and sequential addition of
1
3
, 300 MHz) d 5.27 (t, J ¼ 3.5 Hz, 1H), 4.96 (s, 1H),
4
2
3
1
3
2
Et
extracted with EtOAc (3 ꢁ 10 mL). The combined organic layer
were washed with brine, dried over anhydrous Na SO
filtered, and evaporated to dryness. The residue was purified
by flash chromatography (SiO , petroleum ether/ethyl acetate
3 3
N (4 mL) and NaHCO saturated aqueous (30 mL), and then
13
2
4
,
5.6, 25.5, 25.4, 23.7, 23.6, 23.5, 21.3, 18.2, 16.7, 16.5, 15.6. MS
2
þ
(
(
ESI) m/z: 581.35 [MþNa] . ESI-HRMS calcd. for C34
H
O
54 2
S
2
Na
350:1) to give 17 (1.1 g, 73% yield) as a white amorphous solid.
þ
ꢀ1
[MþNa] ): 581.3463; found: 581.3482.
[a]
D
¼ ꢀ9.3 (c ¼ 0.3, CHCl
3
). FT-IR n (cm ): 3436, 2939, 2873,
1
1
3
733, 1639, 1452, 1384, 1251, 1030, 978, 890. H NMR (CDCl ,
b-Amyrin (2)
300 MHz) d 4.99 (s, 1H), 4.75 (s, 1H), 4.61 (s, 1H), 4.50–4.45 (m,
1H), 3.34–3.25 (m, 1H), 3.18–3.06 (m, 3H), 2.92–2.82 (m, 1H),
2.25–0.78 (m, 24H), 2.04 (s, 3H), 1.73 (s, 3H), 1.04 (s, 3H), 1.00 (s,
According to the procedure for preparation of 1, 2 was
prepared from 14 over two steps as a white amorphous solid
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