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SAC Derivatives as ChE Inhibitors
KOREAN CHEMICAL SOCIETY
diacetyl-protected caffeic acid (AcCA, 100 mg, 0.38 mmol)
and SAC methyl ester (1, 110 mg, 0.45 mmol). H NMR
Isopropyl
2-(5-(1,2-dithiolan-3-yl)pentanamido)-3-
1
(allylthio)propanoate (8): To a mixture of ALA (200 mg,
0.96 mmol), DMAP (5 mg, 0.01 mmol), and EDC (220 mg,
1.16 mmol) in 10 mL DCM, a mixture of SAC IPA ester (7,
280 mg, 1.16 mmol) and TEA (0.41 mL, 2.91 mmol) was
added dropwise. The reaction mixture was stirred for 3 h at
rt and then extracted with DCM (10 mL × 3). The combined
organic layer was dried over anhydrous MgSO4. After the
organicsolventwasremoved undervacuum, thecrudeproduct
was purified by column chromatography (EA/Hex = 1:1) to
(400 MHz, CDCl3) 2.26 (s, 3H), 2.27 (s, 3H), 2.90 (dd, J =
14 Hz, J = 6 Hz, 1H), 2.99 (dd, J = 14 Hz, J = 4.8 Hz, 1H),
3.09 (m, 2H), 3.75 (s, 3H), 4.90 (dt, J = 5.2 Hz, J = 7.6 Hz,
1H), 5.07 (d, J = 10.4 Hz, 1H), 5.08 (d, J = 17.2 Hz, 1H),
5.70 (m, 1H), 6.37 (d, J = 16 Hz, 1H), 6.62 (d, J = 7.6 Hz,
1H), 7.15 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 2 Hz, 1H), 7.32
(dd, J = 8.0 Hz, J = 2 Hz, 1H), 7.53 (d, J = 16 Hz, 1H). 13C
NMR (100 MHz, CDCl3) 20.5 (2C), 32.6, 35.1, 51.8, 52.6,
117.9, 120.9, 122.4, 123.7, 126.2, 133.4 (2C), 140.1, 142.3,
143.1, 164.9, 167.9, 168.0, 171.2. ESI-MS: m/z [M + H]+
422.1 (calcd 421.4).
1
give 2 as a yellow solid product (250 mg, 65% yield). H
NMR (400 MHz, CDCl3) 1.23 (d, J = 6.4 Hz, 6H), 1.45 (m,
2H), 1.64 (m, 4H), 1.86 (m, 1H), 2.21 (t, J = 7.2 Hz, 2H),
2.41 (m, 1H), 2.81 (dd, J = 13.6 Hz, J = 5.2 Hz, 1H), 2.94
(dd, J = 13.2 Hz, J = 4.0 Hz, 1H), 3.08 (d, J = 7.2 Hz, 2H),
3.09 (m, 2H), 3.52 (m, 1H), 4.76 (td, J = 5.2 Hz, J = 7.6 Hz,
1H), 5.02 (m, 1H), 5.07 (d, J = 10.8 Hz, 1H), 5.08 (d, J =
16.0 Hz, 1H), 5.70 (m, 1H), 6.15 (Br-d, J = 7.2 Hz, 1H). 13C
NMR (100 MHz, CDCl3) 21.6, 21.7, 25.1, 28.7, 32.9, 34.5,
35.1, 36.1, 38.4, 40.1, 51.6, 56.3, 69.6, 117.7, 133.5, 170.3,
172.2. ESI-MS: m/z [M + H]+ 392.1 (calcd 391.6).
(E)-Isopropyl 3-(allylthio)-2-(3-(3,4-dimethoxyphenyl)
acrylamido)propanoate (9): Compound 9 (300 mg, 75%
yield) was obtained by using 3,4-dimethoxy cinnamic acid
(DMCA, 200 mg, 0.96 mmol) and SAC IPA ester (7, 253
mg, 1.06 mmol). 1H NMR (400 MHz, CDCl3) 1.30 (d, J = 6
Hz, 6H), 2.95 (dd, J = 13.6 Hz, J = 5.2 Hz, 1H), 3.06 (dd,
J = 13.6 Hz, J = 4.8 Hz, 1H), 3.16 (m, 2H), 3.91 (s, 3H),
3.921 (s, 3H), 3.92 (s, 3H), 4.91 (m, 1H), 5.11 (m, 1H),
5.13 (d, J = 9.6 Hz, 1H), 5.14 (d, J = 16 Hz, 1H), 5.76 (m,
1H), 6.36 (d, J = 15.6 Hz, 1H), 6.38 (d, J = 7.6 Hz, 1H),
6.87 (d, J = 8.4 Hz, 1H), 7.05 (s, 1H), 7.10 (d, J = 8.4 Hz,
1H), 7.60 (d, J = 15.6 Hz, 1H). 13C NMR (100 MHz, CDCl3)
21.6, 21.7, 32.9, 35.3, 52.0, 55.8, 55.9, 69.7, 109.5, 111.0,
117.7 (2C), 122.1, 127.5, 133.5, 141.6, 149.1, 150.7, 165.5,
170.4. ESI-MS: m/z [M + H]+ 394.1 (calcd 393.5).
(E)-4-(3-((3-(Allylthio)-1-isopropoxy-1-oxopropan-2-
yl)amino)-3-oxoprop-1-en-1-yl)-1,2-phenylene diacetate
(10): Compound 10 (180 mg, 52% yield) was obtained by
using diacetyl-protected caffeic acid (AcCA, 200 mg, 0.85
mmol) and SAC IPA ester (7, 244 mg, 1.02 mmol). 1H
NMR (400 MHz, CDCl3) 1.24 (d, J = 5.6 Hz, 6H), 2.24 (s,
3H), 2.25 (s, 3H), 2.89 (dd, J = 14 Hz, J = 5.2 Hz, 1H), 2.99
(dd, J = 14 Hz, J = 4.8 Hz, 1H), 3.10 (m, 2H), 4.89 (dt, J =
5.6 Hz, J = 7.2 Hz, 1H), 5.03 (m, 1H), 5.07 (d, J = 11.6 Hz,
1H), 5.08 (d, J = 16 Hz, 1H), 5.70 (m, 1H), 6.36 (d, J = 15.2
Hz, 1H), 6.45 (d, J = 7.2 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H),
7.29 (s, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 15.6 Hz,
1H). 13C NMR (100 MHz, CDCl3) 20.5 (2C), 21.6, 21.7,
32.8, 35.2, 52.1, 69.8, 117.8, 121.0, 122.4, 123.7, 126.2,
133.5 (2C), 139.9, 142.3, 143.0, 164.8, 167.9, 168.0, 170.2.
ESI-MS: m/z [M + H]+ 450.1 (calcd 449.5).
(E)-Methyl 2-(3-(4-acetoxy-3-methoxyphenyl)acryla-
mido)-3-(allylthio)propanoate (5): Compound 5 (100 mg,
65% yield) was obtained by using acetyl-protected feruric acid
(AcFA, 100 mg, 0.42 mmol) and SAC methyl ester (1, 110 mg,
1
0.51 mmol). H NMR (400 MHz, CDCl3) 2.25 (s, 3H), 2.86
(dd, J = 14 Hz, J = 6.0 Hz, 1H), 2.97 (dd, J = 14 Hz, J = 5.4
Hz, 1H), 3.06 (m, 2H), 3.71 (s, 3H), 3.76 (s, 3H), 4.89 (m,
1H), 5.03 (d, J = 10.4 Hz, 1H), 5.04 (d, J = 17.2 Hz, 1H),
5.67 (m, 1H), 6.39 (d, J = 15.6 Hz, 1H), 6.72 (d, J = 7.6 Hz,
1H), 6.94 (d, J = 8.0 Hz, 1H), 6.99 (s, 1H), 7.00 (d, J = 8.0
Hz, 1H), 7.51 (d, J = 15.6 Hz, 1H). 13C NMR (100 MHz,
CDCl3) 20.5, 32.5, 35.0, 51.9, 52.5, 55.8, 111.4, 117.8,
120.1, 120.7, 123.0, 133.4, 133.6, 140.9, 141.0, 151.2, 165.3,
168.7, 171.3. ESI-MS: m/z [M + H]+ 394.1 (calcd 393.4).
Methyl
2-(4-acetoxy-3,5-dimethoxybenzamido)-3-
(allylthio)propanoate (6): Compound 6 (120 mg, 60% yield)
was obtained by using acetyl-protected syringic acid (AcSA,
100 mg, 0.42 mmol) and SAC methyl ester (1, 110 mg, 0.50
1
mmol). H NMR (400 MHz, CDCl3) 2.30 (s, 3H), 2.95 (dd,
J = 14 Hz, J = 5.6 Hz, 1H), 3.05 (dd, J = 14 Hz, J = 5.4 Hz,
1H), 3.09 (m, 2H), 3.77 (s, 3H), 3.83 (s, 6H), 4.93 (dt, J =
5.2 Hz, J = 7.2 Hz, 1H), 5.07 (d, J = 15.6 Hz, 1H), 5.08 (d,
J = 11.2 Hz, 1H), 5.71 (m, 1H), 6.84 (d, J = 7.2 Hz, 1H),
7.01 (s, 2H). 13C NMR (100 MHz, CDCl3) 20.3, 32.6, 35.1,
52.1, 52.7, 56.3 (2C), 103.9 (2C), 117.9, 131.6, 132.0,
133.4, 152.3 (2C), 166.4, 168.2, 171.3. ESI-MS: m/z [M +
H]+ 398.1 (calcd 397.4).
(R)-3-(Allylthio)-1-isopropoxy-1-oxopropan-2-aminium
chloride (7): To a solution of SAC (100 mg, 0.62 mmol) in 10
mL IPA, thionyl chloride (0.14 mL, 1.86 mmol) was dropwise
added at rt. The mixture was refluxed for 1 h, and then the unre-
active thionyl chloride was removed under vacuum. After tol-
uene (10 mL) was added to the residue, the organic layer was
washed with water and brine. The organic layer was dried over
anhydrous MgSO4. After the organic solvent was removed
under vacuum, the SAC IPA ester was obtained (120 mg,
1
80% yield). H NMR (400 MHz, D2O) 1.18 (d, J = 7.2 Hz,
6H), 2.88 (dd, J = 14.8 Hz, J = 8.0 Hz, 1H), 3.02 (dd, J =
14.8 Hz, J = 4.8 Hz, 1H), 3.11 (m, 2H), 4.15 (dd, J = 8.0 Hz,
J = 4.4 Hz, 1H), 4.99 (h, J = 7.2 Hz, 1H), 5.09 (d, J = 9.6 Hz,
1H), 5.10 (d, J = 17.2 Hz, 1H), 5.71 (m, 1H). 13C NMR
(100 MHz, CDCl3) 20.6 (2C), 29.9, 34.1, 52.3, 72.5, 118.4,
133.1, 168.3. ESI-MS: m/z [M + H]+ 204.1 (calcd 203.7).
(E)-Isopropyl 2-(3-(4-acetoxy-3-methoxyphenyl)acry-
lamido)-3-(allylthio)propanoate (11): Compound 11 (320
mg, 36% yield) was obtained by using acetyl-protected feruric
acid (AcFA, 500 mg, 2.12 mmol) and SAC IPA ester (7, 610
Bull. Korean Chem. Soc. 2015, Vol. 36, 52–58
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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