药学学报


10a	H	H	H	H	77.23	97-99	Light yellow solid
10b	H	CH₃	H	H	56.15	114-116	Light yellow solid
10c	H	H	CH₃	H	61.41	114-116	Light yellow solid
10d	OCH₃	H	H	H	88.38	-	Yellow oil
10e	H	OCH₃	H	H	65.04	82-84	White solid
10f	H	H	OCH₃	H	80.04	106-108	Light yellow solid
10g	H	OCH₃	OCH₃	H	62.55	139-141	Light yellow solid
10h	H	OCH₃	H	OCH₃	67.12	112-114	White solid
10i	H	OCH₃	OCH₃	OCH₃	61.85	142-144	White solid
10j	H	H	OAc	H	50.63	122-123	White solid
10k	H	F	H	H	69.29	96-98	White solid
10l	H	H	F	H	72.75	105-107	Light yellow solid
10m	H	Cl	H	H	52.64	115-116	White solid
10n	H	H	Cl	H	57.58	137-139	Light yellow solid
10o	H	H	NO₂	H	62.15	134-136	Yellow solid
10p	H	H	CF₃	H	52.21	134-136	White solid
11a	H	OH	H	H	71.13	117-120	White solid
11b	H	H	OH	H	62.76	192-193	Light yellow solid
11c	H	OH	OH	H	59.78	201-202	Light yellow solid
11d	H	OH	H	OH	56.52	177-180	Light yellow solid


10a	H	H	H	H	77.23	97-99	Light yellow solid
10b	H	CH₃	H	H	56.15	114-116	Light yellow solid
10c	H	H	CH₃	H	61.41	114-116	Light yellow solid
10d	OCH₃	H	H	H	88.38	-	Yellow oil
10e	H	OCH₃	H	H	65.04	82-84	White solid
10f	H	H	OCH₃	H	80.04	106-108	Light yellow solid
10g	H	OCH₃	OCH₃	H	62.55	139-141	Light yellow solid
10h	H	OCH₃	H	OCH₃	67.12	112-114	White solid
10i	H	OCH₃	OCH₃	OCH₃	61.85	142-144	White solid
10j	H	H	OAc	H	50.63	122-123	White solid
10k	H	F	H	H	69.29	96-98	White solid
10l	H	H	F	H	72.75	105-107	Light yellow solid
10m	H	Cl	H	H	52.64	115-116	White solid
10n	H	H	Cl	H	57.58	137-139	Light yellow solid
10o	H	H	NO₂	H	62.15	134-136	Yellow solid
10p	H	H	CF₃	H	52.21	134-136	White solid
11a	H	OH	H	H	71.13	117-120	White solid
11b	H	H	OH	H	62.76	192-193	Light yellow solid
11c	H	OH	OH	H	59.78	201-202	Light yellow solid
11d	H	OH	H	OH	56.52	177-180	Light yellow solid

Compd.	¹H NMR, ¹³C NMR, ESI-MS
10a	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.65 (d, J = 7.2 Hz, 2H, Ar-H), 7.51-7.36 (m, 4H), 7.31 (d, J = 7.2 Hz, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.02 (m, 1H, CH₂a), 1.77-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.54, 138.95, 137.15, 132.89, 130.71, 129.20, 128.49, 127.35, 127.17, 126.57, 123.32, 122.62, 81.59, 33.99, 26.93, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₂: m/z 293.34 [M+H]⁺.
10b	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.49-7.36 (m, 4H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 7.6 Hz, 1H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.34 (s, 3H, Ar-CH₃), 2.12-2.00 (m, 1H, CH₂a), 1.77-1.63 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 149.49, 139.02, 138.25, 137.08, 132.84, 130.79, 129.21, 129.07, 127.65, 127.18, 126.57, 124.48, 123.31, 122.56, 81.57, 34.00, 26.92, 22.35, 21.48, 14.25; ESI-MS for C₂₁H₂₂O₂: m/z 307.22 [M+H]⁺.
10c	¹H NMR (400 MHz, DMSO-d₆) δ: 8.01 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (d, J = 8.0 Hz, 2H, Ar-H), 7.41 (d, J = 16.4 Hz, 1H, =CH), 7.33 (d, J = 16.4 Hz, 1H, =CH), 7.21 (d, J = 8.0 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.32 (s, 3H, Ar-CH₃), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.32, 139.10, 137.95, 134.37, 132.73, 130.62, 129.78, 127.11, 126.54, 126.31, 123.25, 122.43, 81.56, 34.02, 26.95, 22.36, 21.33, 14.26; ESI-MS for C₂₁H₂₂O₂: m/z 307.14 [M+H]⁺.
10d	¹H NMR (400 MHz, DMSO-d₆) δ: 7.98 (d, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.70-7.64 (m, 2H, Ar-H), 7.55 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.34-7.26 (m, 1H, Ar-H), 7.06 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (t, J = 8.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 3.88 (s, 3H, Ar-OCH₃), 2.11-2.02 (m, 1H, CH₂a), 1.76-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.24, 157.18, 149.39, 139.34, 132.58, 129.83, 127.79, 127.10, 126.55, 125.46, 125.27, 123.29, 122.48, 121.04, 111.84, 81.56, 55.91, 34.01, 26.94, 22.36, 14.24; ESI-MS for C₂₁H₂₂O₃: m/z 323.11 [M+H]⁺.
10e	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.43 (s, 2H, =CH×2), 7.32 (t, J = 8.0 Hz, 1H, Ar-H), 7.25-7.20 (m, 2H, Ar-H), 6.92-6.86 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.81 (s, 3H, Ar-OCH₃), 2.14-2.01 (m, 1H, CH₂a), 1.79-1.66 (m, 1H, CH₂b), 1.45-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.27, 160.04, 149.56, 138.90, 138.60, 132.88, 130.63, 130.18, 127.64, 126.56, 123.32, 122.62, 119.75, 114.26, 112.23, 81.59, 55.51, 33.98, 26.95, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 322.92 [M+H]⁺.
10f	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (d, J = 8.8 Hz, 2H, Ar-H), 7.40 (d, J = 16.4 Hz, 1H, =CH), 7.24 (d, J = 16.4 Hz, 1H, =CH), 6.97 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.79 (s, 3H, Ar-OCH₃), 2.14-2.00 (m, 1H, CH₂a), 1.78-1.63 (m, 1H, CH₂b), 1.42-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 159.73, 149.08, 139.34, 132.60, 130.37, 129.76, 128.54, 126.52, 124.99, 123.25, 122.17, 114.65, 81.57, 55.61, 34.00, 26.94, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 323.16 [M+H]⁺.
10g	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.96 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.32-7.26 (m, 2H), 7.15 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 3H, Ar-OCH₃), 3.78 (s, 3H, Ar-OCH₃), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 149.51, 149.37, 149.05, 139.35, 132.53, 130.72, 130.05, 126.53, 125.12, 123.24, 122.12, 120.78, 112.09, 109.74, 81.58, 55.90, 34.04, 26.99, 22.36, 14.25; ESI-MS for C₂₂H₂₄O₄: m/z 353.10 [M+H]⁺.
10h	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.44 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 6.83 (d, J = 2.4 Hz, 2H, Ar-H), 6.46 (t, J = 2.4 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.80 (s, 6H, Ar-OCH₃), 2.13-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.45-1.21 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 161.12, 149.56, 139.15, 138.85, 132.84, 130.70, 127.84, 126.56, 123.27, 122.63, 105.17, 100.62, 81.59, 55.63, 34.02, 26.99, 22.36, 14.24; ESI-MS for C₂₂H₂₄O₄: m/z 353.23 [M+H]⁺; HR-MS (ESI⁺) [M+H]⁺: m/z Calcd. for C₂₂H₂₄O₄: 353.174 7; Found: 353.174 5.
10i	¹H NMR (400 MHz, DMSO-d₆) δ: 8.02 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.40 (s, 2H, Ar-H), 6.99 (s, 2H, =CH×2), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 6H, Ar-OCH₃), 3.69 (s, 3H, Ar-OCH₃), 2.12-2.01 (m, 1H, CH₂a), 1.76-1.65 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 153.52, 149.32, 139.09, 138.06, 132.87, 132.68, 130.85, 126.65, 126.57, 123.31, 122.30, 104.56, 81.60, 60.52, 56.28, 34.03, 26.99, 22.36, 14.24; ESI-MS for C₂₃H₂₆O₅: m/z 383.06 [M+H]⁺; HR-MS (ESI⁺) [M+Na]⁺: m/z Calcd. for C₂₃H₂₆O₅: 405.167 2; Found: 405.167 0.
10j	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.71-7.65 (m, 3H, Ar-H), 7.48 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 8.8 Hz, Ar-H), 5.65 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.29 (s, 3H, COCH₃), 2.14-2.02 (m, 1H, CH₂a), 1.78-1.66 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 169.64, 150.64, 149.58, 138.90, 134.87, 132.92, 129.79, 128.14, 127.49, 126.57, 123.35, 122.64, 81.60, 33.97, 26.92, 22.36, 21.33, 14.27; ESI-MS for C₂₂H₂₂O₄: m/z 351.09 [M+H]⁺.
10k	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.55-7.40 (m, 5H), 7.17-7.09 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ:170.21, 163.05 (J_C-F = 241.9 Hz), 149.84, 139.86 (J_C-F = 7.8 Hz), 138.57, 133.06, 131.07 (J_C-F = 8.6 Hz), 129.45 (J_C-F = 2.7 Hz), 128.92, 126.58, 123.60 (J_C-F = 2.7 Hz), 123.37, 122.76, 115.09 (J_C-F = 21.1 Hz), 113.14 (J_C-F = 21.8 Hz), 81.61, 33.96, 26.93, 22.35, 14.25; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10l	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73-7.64 (m, 3H, Ar-H), 7.47 (d, J = 16.4 Hz, 1H, =CH), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.29-7.20 (m, 2H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 162.34 (J_C-F = 244.1 Hz), 149.50, 138.88, 133.75 (J_C-F = 3.0 Hz), 132.85, 129.52, 129.06 (J_C-F = 8.0 Hz), 127.23 (J_C-F = 2.4 Hz), 126.55, 122.90 (J_C-F = 77.2 Hz), 116.18, 115.97, 81.58, 33.99, 26.93, 22.35, 14.23; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10m	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73 (t, J = 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.59 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 16.4 Hz, 1H, =CH), 7.48-7.39 (m, 2H), 7.38-7.32 (m, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.21, 149.86, 139.50, 138.56, 134.07, 133.08, 130.97, 129.15, 129.04, 128.08, 126.57, 125.87, 123.36, 122.80, 81.60, 33.97, 26.94, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.8 [M+H]⁺.
10n	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.72-7.63 (m, 3H, Ar-H), 7.51-7.38 (m, 4H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.23, 149.69, 138.69, 136.11, 132.99, 132.80, 129.35, 129.18, 128.77, 128.18, 126.57, 123.31, 122.69, 81.60, 33.98, 26.95, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.9 [M+H]⁺.
10o	¹H NMR (400 MHz, DMSO-d₆) δ: 8.24 (d, J = 8.8 Hz, 2H, Ar-H), 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.87 (d, J = 8.8 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.66 (d, J = 16.4 Hz, 1H, =CH), 7.61 (d, J = 16.4 Hz, 1H, =CH), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.10, 150.40, 146.81, 144.03, 138.13, 133.44, 132.01, 128.55, 127.94, 126.63, 124.45, 123.44, 123.27, 81.64, 33.93, 26.98, 22.35, 14.24; ESI-MS for C₂₀H₁₉NO₄: m/z 337.9 [M+H]⁺.
10p	¹H NMR (400 MHz, DMSO-d₆) δ: 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.85 (d, J = 8.4 Hz, 2H, Ar-H), 7.76 (d, J = 8.4 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (s, 2H, =CH×2), 5.66 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.02 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.17, 150.07, 141.27, 138.38, 133.22, 130.20, 129.11, 128.32 (J_C-F = 31.6 Hz), 127.63, 126.60, 126.02 (J_C-F = 3.9 Hz), 124.74 (J_C-F = 269.8 Hz), 123.37, 123.03, 81.60, 33.96, 26.95, 22.34, 14.21; ESI-MS for C₂₁H₁₉F₃O₂: m/z 360.9 [M+H]⁺.
11a	¹H NMR (400 MHz, DMSO-d₆) δ: 9.48 (s, 1H, Ar-OH), 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.37 (d, J = 16.4 Hz, 1H, =CH), 7.30 (d, J = 16.4 Hz, 1H, =CH), 7.19 (t, J = 8.0 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 7.02 (t, J = 2.0 Hz, 1H, Ar-H), 6.72 (dd, J = 8.0, 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.00 (m, 1H, CH₂a), 1.78- 1.64 (m, 1H, CH₂b), 1.44-1.21 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 158.13, 149.46, 138.95, 138.46, 132.85, 130.93, 130.10, 127.12, 126.54, 123.22, 122.65, 118.18, 115.72, 113.81, 81.56, 34.01, 26.94, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₃: m/z 309.04 [M+H]⁺.
11b	¹H NMR (400 MHz, DMSO-d₆) δ: 9.68 (s, 1H, Ar-OH), 8.00-7.92 (m, 2H, Ar-H), 7.64 (d, J = 8.0 Hz, 1H, Ar-H), 7.47 (d, J = 8.8 Hz, 2H, Ar-H), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 16.4 Hz, 1H, =CH), 6.80 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.37, 158.16, 148.88, 139.51, 132.47, 130.77, 128.66, 128.18, 126.50, 123.97, 123.20, 122.02, 116.06, 81.56, 34.03, 26.94, 22.37, 14.27; ESI-MS for C₂₀H₂₀O₃: m/z 309.23 [M+H]⁺.
11c	¹H NMR (400 MHz, DMSO-d₆) δ: 9.19 (s, 1H, Ar-OH), 8.99 (s, 1H, Ar-OH), 7.98-7.92 (m, 2H, Ar-H), 7.62 (d, J = 8.0 Hz, 1H, Ar-H), 7.26 (d, J = 16.4 Hz, 1H, =CH), 7.07 (d, J = 16.4 Hz, 1H, =CH), 6.92 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.76 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.38, 148.84, 146.49, 145.91, 139.52, 132.48, 131.17, 128.75, 126.48, 123.88, 123.17, 122.06, 119.45, 116.17, 114.05, 81.54, 34.02, 26.92, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₄: m/z 325.39 [M+H]⁺.
11d	¹H NMR (400 MHz, DMSO-d₆) δ: 9.30 (s, 2H, Ar-OH), 8.02 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.27 (d, J = 16.4 Hz, 1H, =CH), 7.19 (d, J = 16.4 Hz, 1H, =CH), 6.49 (d, J = 2.0 Hz, 2H, Ar-H), 6.20 (t, J = 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.29, 159.04, 149.40, 138.97, 138.88, 132.84, 131.29, 126.84, 126.51, 123.19, 122.66, 105.44, 103.21, 81.55, 34.00, 26.92, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₄: m/z 325.16 [M+H]⁺.

Compd.	¹H NMR, ¹³C NMR, ESI-MS
10a	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.65 (d, J = 7.2 Hz, 2H, Ar-H), 7.51-7.36 (m, 4H), 7.31 (d, J = 7.2 Hz, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.02 (m, 1H, CH₂a), 1.77-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.54, 138.95, 137.15, 132.89, 130.71, 129.20, 128.49, 127.35, 127.17, 126.57, 123.32, 122.62, 81.59, 33.99, 26.93, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₂: m/z 293.34 [M+H]⁺.
10b	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.49-7.36 (m, 4H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 7.6 Hz, 1H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.34 (s, 3H, Ar-CH₃), 2.12-2.00 (m, 1H, CH₂a), 1.77-1.63 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 149.49, 139.02, 138.25, 137.08, 132.84, 130.79, 129.21, 129.07, 127.65, 127.18, 126.57, 124.48, 123.31, 122.56, 81.57, 34.00, 26.92, 22.35, 21.48, 14.25; ESI-MS for C₂₁H₂₂O₂: m/z 307.22 [M+H]⁺.
10c	¹H NMR (400 MHz, DMSO-d₆) δ: 8.01 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (d, J = 8.0 Hz, 2H, Ar-H), 7.41 (d, J = 16.4 Hz, 1H, =CH), 7.33 (d, J = 16.4 Hz, 1H, =CH), 7.21 (d, J = 8.0 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.32 (s, 3H, Ar-CH₃), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.32, 139.10, 137.95, 134.37, 132.73, 130.62, 129.78, 127.11, 126.54, 126.31, 123.25, 122.43, 81.56, 34.02, 26.95, 22.36, 21.33, 14.26; ESI-MS for C₂₁H₂₂O₂: m/z 307.14 [M+H]⁺.
10d	¹H NMR (400 MHz, DMSO-d₆) δ: 7.98 (d, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.70-7.64 (m, 2H, Ar-H), 7.55 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.34-7.26 (m, 1H, Ar-H), 7.06 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (t, J = 8.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 3.88 (s, 3H, Ar-OCH₃), 2.11-2.02 (m, 1H, CH₂a), 1.76-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.24, 157.18, 149.39, 139.34, 132.58, 129.83, 127.79, 127.10, 126.55, 125.46, 125.27, 123.29, 122.48, 121.04, 111.84, 81.56, 55.91, 34.01, 26.94, 22.36, 14.24; ESI-MS for C₂₁H₂₂O₃: m/z 323.11 [M+H]⁺.
10e	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.43 (s, 2H, =CH×2), 7.32 (t, J = 8.0 Hz, 1H, Ar-H), 7.25-7.20 (m, 2H, Ar-H), 6.92-6.86 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.81 (s, 3H, Ar-OCH₃), 2.14-2.01 (m, 1H, CH₂a), 1.79-1.66 (m, 1H, CH₂b), 1.45-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.27, 160.04, 149.56, 138.90, 138.60, 132.88, 130.63, 130.18, 127.64, 126.56, 123.32, 122.62, 119.75, 114.26, 112.23, 81.59, 55.51, 33.98, 26.95, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 322.92 [M+H]⁺.
10f	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (d, J = 8.8 Hz, 2H, Ar-H), 7.40 (d, J = 16.4 Hz, 1H, =CH), 7.24 (d, J = 16.4 Hz, 1H, =CH), 6.97 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.79 (s, 3H, Ar-OCH₃), 2.14-2.00 (m, 1H, CH₂a), 1.78-1.63 (m, 1H, CH₂b), 1.42-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 159.73, 149.08, 139.34, 132.60, 130.37, 129.76, 128.54, 126.52, 124.99, 123.25, 122.17, 114.65, 81.57, 55.61, 34.00, 26.94, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 323.16 [M+H]⁺.
10g	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.96 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.32-7.26 (m, 2H), 7.15 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 3H, Ar-OCH₃), 3.78 (s, 3H, Ar-OCH₃), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 149.51, 149.37, 149.05, 139.35, 132.53, 130.72, 130.05, 126.53, 125.12, 123.24, 122.12, 120.78, 112.09, 109.74, 81.58, 55.90, 34.04, 26.99, 22.36, 14.25; ESI-MS for C₂₂H₂₄O₄: m/z 353.10 [M+H]⁺.
10h	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.44 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 6.83 (d, J = 2.4 Hz, 2H, Ar-H), 6.46 (t, J = 2.4 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.80 (s, 6H, Ar-OCH₃), 2.13-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.45-1.21 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 161.12, 149.56, 139.15, 138.85, 132.84, 130.70, 127.84, 126.56, 123.27, 122.63, 105.17, 100.62, 81.59, 55.63, 34.02, 26.99, 22.36, 14.24; ESI-MS for C₂₂H₂₄O₄: m/z 353.23 [M+H]⁺; HR-MS (ESI⁺) [M+H]⁺: m/z Calcd. for C₂₂H₂₄O₄: 353.174 7; Found: 353.174 5.
10i	¹H NMR (400 MHz, DMSO-d₆) δ: 8.02 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.40 (s, 2H, Ar-H), 6.99 (s, 2H, =CH×2), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 6H, Ar-OCH₃), 3.69 (s, 3H, Ar-OCH₃), 2.12-2.01 (m, 1H, CH₂a), 1.76-1.65 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 153.52, 149.32, 139.09, 138.06, 132.87, 132.68, 130.85, 126.65, 126.57, 123.31, 122.30, 104.56, 81.60, 60.52, 56.28, 34.03, 26.99, 22.36, 14.24; ESI-MS for C₂₃H₂₆O₅: m/z 383.06 [M+H]⁺; HR-MS (ESI⁺) [M+Na]⁺: m/z Calcd. for C₂₃H₂₆O₅: 405.167 2; Found: 405.167 0.
10j	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.71-7.65 (m, 3H, Ar-H), 7.48 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 8.8 Hz, Ar-H), 5.65 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.29 (s, 3H, COCH₃), 2.14-2.02 (m, 1H, CH₂a), 1.78-1.66 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 169.64, 150.64, 149.58, 138.90, 134.87, 132.92, 129.79, 128.14, 127.49, 126.57, 123.35, 122.64, 81.60, 33.97, 26.92, 22.36, 21.33, 14.27; ESI-MS for C₂₂H₂₂O₄: m/z 351.09 [M+H]⁺.
10k	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.55-7.40 (m, 5H), 7.17-7.09 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ:170.21, 163.05 (J_C-F = 241.9 Hz), 149.84, 139.86 (J_C-F = 7.8 Hz), 138.57, 133.06, 131.07 (J_C-F = 8.6 Hz), 129.45 (J_C-F = 2.7 Hz), 128.92, 126.58, 123.60 (J_C-F = 2.7 Hz), 123.37, 122.76, 115.09 (J_C-F = 21.1 Hz), 113.14 (J_C-F = 21.8 Hz), 81.61, 33.96, 26.93, 22.35, 14.25; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10l	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73-7.64 (m, 3H, Ar-H), 7.47 (d, J = 16.4 Hz, 1H, =CH), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.29-7.20 (m, 2H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 162.34 (J_C-F = 244.1 Hz), 149.50, 138.88, 133.75 (J_C-F = 3.0 Hz), 132.85, 129.52, 129.06 (J_C-F = 8.0 Hz), 127.23 (J_C-F = 2.4 Hz), 126.55, 122.90 (J_C-F = 77.2 Hz), 116.18, 115.97, 81.58, 33.99, 26.93, 22.35, 14.23; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10m	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73 (t, J = 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.59 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 16.4 Hz, 1H, =CH), 7.48-7.39 (m, 2H), 7.38-7.32 (m, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.21, 149.86, 139.50, 138.56, 134.07, 133.08, 130.97, 129.15, 129.04, 128.08, 126.57, 125.87, 123.36, 122.80, 81.60, 33.97, 26.94, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.8 [M+H]⁺.
10n	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.72-7.63 (m, 3H, Ar-H), 7.51-7.38 (m, 4H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.23, 149.69, 138.69, 136.11, 132.99, 132.80, 129.35, 129.18, 128.77, 128.18, 126.57, 123.31, 122.69, 81.60, 33.98, 26.95, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.9 [M+H]⁺.
10o	¹H NMR (400 MHz, DMSO-d₆) δ: 8.24 (d, J = 8.8 Hz, 2H, Ar-H), 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.87 (d, J = 8.8 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.66 (d, J = 16.4 Hz, 1H, =CH), 7.61 (d, J = 16.4 Hz, 1H, =CH), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.10, 150.40, 146.81, 144.03, 138.13, 133.44, 132.01, 128.55, 127.94, 126.63, 124.45, 123.44, 123.27, 81.64, 33.93, 26.98, 22.35, 14.24; ESI-MS for C₂₀H₁₉NO₄: m/z 337.9 [M+H]⁺.
10p	¹H NMR (400 MHz, DMSO-d₆) δ: 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.85 (d, J = 8.4 Hz, 2H, Ar-H), 7.76 (d, J = 8.4 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (s, 2H, =CH×2), 5.66 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.02 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.17, 150.07, 141.27, 138.38, 133.22, 130.20, 129.11, 128.32 (J_C-F = 31.6 Hz), 127.63, 126.60, 126.02 (J_C-F = 3.9 Hz), 124.74 (J_C-F = 269.8 Hz), 123.37, 123.03, 81.60, 33.96, 26.95, 22.34, 14.21; ESI-MS for C₂₁H₁₉F₃O₂: m/z 360.9 [M+H]⁺.
11a	¹H NMR (400 MHz, DMSO-d₆) δ: 9.48 (s, 1H, Ar-OH), 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.37 (d, J = 16.4 Hz, 1H, =CH), 7.30 (d, J = 16.4 Hz, 1H, =CH), 7.19 (t, J = 8.0 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 7.02 (t, J = 2.0 Hz, 1H, Ar-H), 6.72 (dd, J = 8.0, 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.00 (m, 1H, CH₂a), 1.78- 1.64 (m, 1H, CH₂b), 1.44-1.21 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 158.13, 149.46, 138.95, 138.46, 132.85, 130.93, 130.10, 127.12, 126.54, 123.22, 122.65, 118.18, 115.72, 113.81, 81.56, 34.01, 26.94, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₃: m/z 309.04 [M+H]⁺.
11b	¹H NMR (400 MHz, DMSO-d₆) δ: 9.68 (s, 1H, Ar-OH), 8.00-7.92 (m, 2H, Ar-H), 7.64 (d, J = 8.0 Hz, 1H, Ar-H), 7.47 (d, J = 8.8 Hz, 2H, Ar-H), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 16.4 Hz, 1H, =CH), 6.80 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.37, 158.16, 148.88, 139.51, 132.47, 130.77, 128.66, 128.18, 126.50, 123.97, 123.20, 122.02, 116.06, 81.56, 34.03, 26.94, 22.37, 14.27; ESI-MS for C₂₀H₂₀O₃: m/z 309.23 [M+H]⁺.
11c	¹H NMR (400 MHz, DMSO-d₆) δ: 9.19 (s, 1H, Ar-OH), 8.99 (s, 1H, Ar-OH), 7.98-7.92 (m, 2H, Ar-H), 7.62 (d, J = 8.0 Hz, 1H, Ar-H), 7.26 (d, J = 16.4 Hz, 1H, =CH), 7.07 (d, J = 16.4 Hz, 1H, =CH), 6.92 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.76 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.38, 148.84, 146.49, 145.91, 139.52, 132.48, 131.17, 128.75, 126.48, 123.88, 123.17, 122.06, 119.45, 116.17, 114.05, 81.54, 34.02, 26.92, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₄: m/z 325.39 [M+H]⁺.
11d	¹H NMR (400 MHz, DMSO-d₆) δ: 9.30 (s, 2H, Ar-OH), 8.02 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.27 (d, J = 16.4 Hz, 1H, =CH), 7.19 (d, J = 16.4 Hz, 1H, =CH), 6.49 (d, J = 2.0 Hz, 2H, Ar-H), 6.20 (t, J = 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.29, 159.04, 149.40, 138.97, 138.88, 132.84, 131.29, 126.84, 126.51, 123.19, 122.66, 105.44, 103.21, 81.55, 34.00, 26.92, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₄: m/z 325.16 [M+H]⁺.

Compd.	Survival rate ± SD
NBP	58.87 ± 1.44	64.63 ± 2.13^**	72.12 ± 1.52^**	87.17 ± 1.24^**
Resveratrol	58.76 ± 1.59	63.22 ± 2.33^**	67.44 ± 2.41^**	79.86 ± 1.93^**
10a	60.00 ± 1.03	64.53 ± 0.78^**	72.38 ± 1.52^**^△△	85.15 ± 1.83^**^△△
10b	59.03 ± 1.77	62.77 ± 2.45^**	67.62 ± 1.59^**##	79.59 ± 1.05^**##
10c	59.67 ± 1.88	63.04 ± 1.45^**	69.68 ± 1.37^**	79.84 ± 1.45^**##
10d	58.57 ± 1.01	59.50 ± 0.98^##^△△	64.64 ± 1.22^**##	66.96 ± 1.41^**##^△△
10e	58.19 ± 1.06	59.61 ± 1.22^##^△	64.64 ± 0.81^**##	66.90 ± 0.64^**##^△△
10f	59.77 ± 2.63	60.83 ± 2.70^##	65.54 ± 2.30^**##	68.49 ± 2.40^**##^△△
10g	58.60 ± 2.89	65.42 ± 0.95^**	72.07 ± 2.70^**^△△	86.36 ± 2.14^**^△△
10h	59.62 ± 0.55	68.59 ± 1.16^**##^△△	79.64 ± 1.84^**##^△△	85.64 ± 0.90^**^△△
10i	58.59 ± 1.03	72.83 ± 1.64^**##^△△	81.75 ± 1.07^**##^△△	88.34 ± 1.34^**^△△
10j	58.77 ± 2.31	67.61 ± 1.43^**^△△	75.36 ± 2.58^**#^△△	81.99 ± 2.69^**##
10k	59.11 ± 1.30	60.14 ± 1.17^##	61.73 ± 2.25^*##^△△	63.41 ± 1.77^**##^△△
10l	59.77 ± 2.03	61.45 ± 2.24^#	62.44 ± 2.22^*##^△△	63.26 ± 2.84^**##^△△
10m	58.75 ± 0.76	59.32 ± 1.48^##^△△	62.37 ± 2.36^**##^△△	64.91 ± 1.71^**##^△△
10n	60.72 ± 1.63	62.13 ± 2.01	63.33 ± 1.89^*##^△△	64.62 ± 1.83^**##^△△
10o	58.30 ± 1.81	59.84 ± 0.68^##^△	62.74 ± 1.95^**##^△△	64.94 ± 1.68^**##^△△
10p	57.90 ± 1.00	67.60 ± 1.65^**^△△	73.79 ± 1.14^**^△△	79.51 ± 1.46^**##
11a	59.56 ± 1.47	66.76 ± 0.51^**^△	72.01 ± 1.33^**^△△	79.99 ± 1.88^**##
11b	59.00 ± 0.69	61.91 ± 0.96^*	68.82 ± 1.37^**#	77.72 ± 1.76^**##
11c	58.36 ± 1.30	61.50 ± 1.96^*	69.72 ± 2.10^**	78.29 ± 1.32^**##
11d	58.68 ± 1.10	62.30 ± 0.94^**	69.40 ± 1.71^**	77.64 ± 0.32^**##

Compd.	Survival rate ± SD
NBP	58.87 ± 1.44	64.63 ± 2.13^**	72.12 ± 1.52^**	87.17 ± 1.24^**
Resveratrol	58.76 ± 1.59	63.22 ± 2.33^**	67.44 ± 2.41^**	79.86 ± 1.93^**
10a	60.00 ± 1.03	64.53 ± 0.78^**	72.38 ± 1.52^**^△△	85.15 ± 1.83^**^△△
10b	59.03 ± 1.77	62.77 ± 2.45^**	67.62 ± 1.59^**##	79.59 ± 1.05^**##
10c	59.67 ± 1.88	63.04 ± 1.45^**	69.68 ± 1.37^**	79.84 ± 1.45^**##
10d	58.57 ± 1.01	59.50 ± 0.98^##^△△	64.64 ± 1.22^**##	66.96 ± 1.41^**##^△△
10e	58.19 ± 1.06	59.61 ± 1.22^##^△	64.64 ± 0.81^**##	66.90 ± 0.64^**##^△△
10f	59.77 ± 2.63	60.83 ± 2.70^##	65.54 ± 2.30^**##	68.49 ± 2.40^**##^△△
10g	58.60 ± 2.89	65.42 ± 0.95^**	72.07 ± 2.70^**^△△	86.36 ± 2.14^**^△△
10h	59.62 ± 0.55	68.59 ± 1.16^**##^△△	79.64 ± 1.84^**##^△△	85.64 ± 0.90^**^△△
10i	58.59 ± 1.03	72.83 ± 1.64^**##^△△	81.75 ± 1.07^**##^△△	88.34 ± 1.34^**^△△
10j	58.77 ± 2.31	67.61 ± 1.43^**^△△	75.36 ± 2.58^**#^△△	81.99 ± 2.69^**##
10k	59.11 ± 1.30	60.14 ± 1.17^##	61.73 ± 2.25^*##^△△	63.41 ± 1.77^**##^△△
10l	59.77 ± 2.03	61.45 ± 2.24^#	62.44 ± 2.22^*##^△△	63.26 ± 2.84^**##^△△
10m	58.75 ± 0.76	59.32 ± 1.48^##^△△	62.37 ± 2.36^**##^△△	64.91 ± 1.71^**##^△△
10n	60.72 ± 1.63	62.13 ± 2.01	63.33 ± 1.89^*##^△△	64.62 ± 1.83^**##^△△
10o	58.30 ± 1.81	59.84 ± 0.68^##^△	62.74 ± 1.95^**##^△△	64.94 ± 1.68^**##^△△
10p	57.90 ± 1.00	67.60 ± 1.65^**^△△	73.79 ± 1.14^**^△△	79.51 ± 1.46^**##
11a	59.56 ± 1.47	66.76 ± 0.51^**^△	72.01 ± 1.33^**^△△	79.99 ± 1.88^**##
11b	59.00 ± 0.69	61.91 ± 0.96^*	68.82 ± 1.37^**#	77.72 ± 1.76^**##
11c	58.36 ± 1.30	61.50 ± 1.96^*	69.72 ± 2.10^**	78.29 ± 1.32^**##
11d	58.68 ± 1.10	62.30 ± 0.94^**	69.40 ± 1.71^**	77.64 ± 0.32^**##

白藜芦醇-丁苯酞杂合物的合成及其神经保护活性

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高燕 ¹ , 刘万冬 ² , 阮班锋 ¹^,^*

药学学报 | 研究论文 2019,54(8): 1461-1469

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药学学报 | 研究论文 2019, 54(8): 1461-1469

白藜芦醇-丁苯酞杂合物的合成及其神经保护活性

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高燕¹, 刘万冬², 阮班锋¹^,^*

作者信息

1.合肥工业大学食品与生物工程学院, 安徽合肥 230009

2.安徽中医药大学药学院, 安徽合肥 230012

通讯作者:

*阮班锋, Tel/Fax:86-551-62901534, E-mail:ruanbf@hfut.edu.cn

Synthesis and neuroprotective activity of resveratrol-3-n-butylphthalide hybrids

Yan GAO¹, Wan-dong LIU², Ban-feng RUAN¹^,^*

Affiliations

1. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China

2. College of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China

出版时间: 2019-08-12 doi: 10.16438/j.0513-4870.2019-0364

文章导航

摘要

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以邻羧基苯甲醛为起始化合物，通过硝化、还原和重氮化等反应得到6-溴丁苯酞，将其与取代苯乙烯偶联得到20个白藜芦醇-丁苯酞杂合物，其结构经¹H NMR、¹³C NMR、ESI-MS确证。采用MTT法考察所有化合物对氧糖剥夺诱导大鼠脑皮层神经元损伤的体外保护活性；采用Western印迹考察目标化合物对大鼠脑皮层神经元保护的作用机制。结果显示，大多数化合物对大鼠脑皮层神经元具有较强的保护作用（动物实验经安徽中医药大学实验动物伦理委员会批准），其中化合物10h和10i活性较为显著，其可能通过激活PI3K/Akt信号通路起到神经保护作用。

关键词

白藜芦醇 / 丁苯酞 / 合成 / 神经保护 / PI3K/Akt

Abstract

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6-Bromo-3-n-butylphthalide was obtained by nitration, reduction and diazotization from carboxybenzaldehyde. Twenty hybrids from substituted styrene and 6-bromo-3-n-butylphthalide were synthesized and the structure was confirmed by ¹H NMR, ¹³C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The mechanism of neuroprotection was investigated by Western blot analyses. The results indicated that most of these compounds had a potent neuroprotective activity (All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine), especially 10h and 10i showed significant effects, which may play a neuroprotective role by activating the PI3K/Akt signaling pathway.

Key words

resveratrol / dl-3-n-butylphthalide / synthesis / neuroprotection / PI3K/Akt

引用本文

高燕, 刘万冬, 阮班锋. 白藜芦醇-丁苯酞杂合物的合成及其神经保护活性. 药学学报, 2019 , 54 (8) : 1461 -1469 . DOI: 10.16438/j.0513-4870.2019-0364

Yan GAO, Wan-dong LIU, Ban-feng RUAN. Synthesis and neuroprotective activity of resveratrol-3-n-butylphthalide hybrids[J]. Acta Pharmaceutica Sinica, 2019 , 54 (8) : 1461 -1469 . DOI: 10.16438/j.0513-4870.2019-0364

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缺血性脑卒中是由多种原因所致的局部脑组织区域血液供应障碍, 导致严重的代谢应激并引发缺血级联, 产生一系列病理性损伤, 如氧化应激、兴奋性氨基酸毒性、钙超载、炎症反应等, 引起神经元凋亡或死亡并产生不可逆的组织损伤(缺血核心)^[1]。组织型纤溶酶原激活剂(t-PA)是迄今为止唯一被美国食品和药品管理局(FDA)批准用于治疗急性缺血性脑卒中的溶栓药物, 但较窄的治疗时间窗及较高的出血转化(HT)发生率限制了t-PA的临床应用, 只有约3.4%~5.2%的急性脑卒中患者能够接受t-PA治疗^[2]。除再灌注策略外, 神经保护一直是脑卒中研究的一个重要领域, 其目标是增强神经元存活率并改善脑卒中的预后。在患者有小血管闭塞的情况下, 采用t-PA治疗或自发再灌注时迫切需要神经保护剂。在较大动脉阻塞引起的缺血性脑卒中患者中, 血管内血栓切除术可提高血管再通率, 但对于神经保护和神经恢复剂同样需求迫切^[3]。

白藜芦醇(resveratrol, 图 1)是具有二苯乙烯结构的天然产物。研究表明, 白藜芦醇具有抗炎和抗氧化特性, 能够增加β-淀粉样蛋白(Aβ)清除率, 调节参与神经细胞存活/死亡的细胞内效应物, 在多种细胞毒性模型中显示出神经保护活性^[4]。天然白藜芦醇衍生物松芪(pinostilbene, 图 1)在SH-SY5Y神经母细胞瘤细胞中发挥有效的神经保护作用, 其有效浓度范围比白藜芦醇更宽^[5]。紫檀芪(pterostilbene, 图 1)低剂量时能显著改善SAMP8小鼠的径向臂水迷宫功能, 以及炎症和细胞应激的正调节, 而白藜芦醇显示无效^[6]。因此, 对白藜芦醇羟基结构修饰能够提高白藜芦醇的神经保护能力。

丁苯酞(dl-3-n-butylphthalide, NBP, 图 1)是我国研制的具有自主知识产权的抗脑缺血药物, 于2002年被批准用作缺血性卒中的治疗。药理学研究表明, NBP在抑制血小板聚集改善微循环的同时, 又能改善线粒体功能, 抑制谷氨酸释放, 阻止神经细胞凋亡, 可作用于脑卒中的多个病理环节。在临床上, 其可作为神经保护剂与其他药物联合使用。此外, 研究表明NBP的衍生物对氧化损伤和细胞凋亡具有很好的保护作用, 丁苯酞可作为神经细胞保护的活性片段, 运用于抗脑缺血药物的研发中^[7-9]。

基于白藜芦醇和丁苯酞良好的神经细胞保护作用, 将两者的结构进行拼合, 期望获得一类新型的神经细胞保护剂。因此, 本文以白藜芦醇为先导化合物, 将丁苯酞替代其结构中的B环片段, 设计合成了20个白藜芦醇-丁苯酞杂合物(图 2), 通过氧糖剥夺/复氧(oxygen-glucose deprivation/reoxygenation, OGD/R)模型检测化合物对神经细胞的保护活性, 并采用Western印迹法对其作用机制进行初步探究。同时对该系列化合物的构效关系进行总结。

结果与讨论

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1 化学合成

目标化合物的合成如合成路线1所示。以市售的邻羧基苯甲醛3为原料, 二乙胺保护羧基, 与正丁基溴化镁反应, 对甲苯磺酸催化得到丁苯酞6; 与硝酸钾和浓硫酸发生硝化反应, 铁粉/氯化铵还原硝基, 桑德迈尔反应得到化合物6-溴丁苯酞9, 该方法与已报道化合物9的合成方法^[10]相比操作简单, 收率更高。化合物1a~1p通过Wittig反应得到化合物2a~2p, 再与9进行Heck反应得到目标化合物10a~10p, 三溴化硼脱甲氧基得到目标化合物11a~11d。所有目标化合物结构均经¹H NMR、¹³C NMR和ESI-MS确证, 其收率、理化常数及波谱数据分别见表 1、2。

2 目标化合物的药理活性

体外抗氧糖剥夺诱导大鼠脑皮层神经元损伤的保护实验结果如表 3所示, 化合物10a~10c、10g~10i、10p和11a~11d与OGD/R相比, 在低中高3种剂量下均能够显著提高细胞存活率(P < 0.05);其中化合物10h与10i的神经保护作用最为突出, 其细胞存活率显著高于先导化合物白藜芦醇以及阳性药丁苯酞, 尤其在剂量为1 μmol·L^-1时, 优于白藜芦醇(67.44 ± 2.41 μmol·L^-1)和丁苯酞(72.12 ± 1.52 μmol·L^-1), 显示出良好的神经保护作用。

依据上述测试结果, 选择化合物10h和10i进一步评价其神经保护作用机制。Western blot结果(图 3)显示, 化合物10h和10i均可呈浓度依赖性地上调Akt磷酸化水平, 化合物在10 μmol·L^-1下可极显著上调Akt磷酸化水平(P < 0.001), 而化合物10h则在低浓度(0.1 μmol·L^-1)下对Akt磷酸化无显著影响; 此外, Control组、OGD/R组和各浓度化合物组中Akt表达无明显差异。结果提示化合物10h和10i可能通过激活PI3K/Akt通路, 上调Akt磷酸化水平起到神经元保护作用。

3 小结

本文采用药效团拼合原理将白藜芦醇和丁苯酞进行拼接, 并设计合成了20个白藜芦醇-丁苯酞杂合物, 目标化合物经¹H NMR、¹³C NMR、ESI-MS确证。经OGD/R模型初步检测目标化合物的神经细胞保护活性, 结果表明大多数化合物都具有良好的神经细胞保护活性, 其中化合物10h和10i在0.1 μmol·L^-1、1 μmol·L^-1剂量下的细胞保护活性, 显著高于先导化合物白藜芦醇以及阳性药丁苯酞。通过初步的机制研究表明, 该系列化合物可能通过激活PI3K/Akt通路实现神经细胞保护活性。初步构效关系表明:剂量为1 μmol·L^-1时(图 4), 除了三氟甲基外, 在目标化合物的A环中引入单个取代基团都会降低化合物的活性(10a > 11a > 10b > 10d > 10n > 10k), 当引入基团为吸电子基团时, 对化合物的活性降低程度更为明显; 针对取代基为甲氧基而言, A环中取代基数量的增加, 化合物的活性明显增强(10d = 10e > 10f > 10g > 10h > 10i), 其中化合物10i表现出最强的细胞保护活性(81.75 ± 1.07 μmol·L^-1)。本研究结果为进一步优化白藜芦醇-丁苯酞杂合物作为神经细胞保护剂提供理论依据。

实验部分

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实验动物 SPF级SD大鼠乳鼠, 购自安徽医科大学实验动物中心, 动物合格证号: SCXK (皖) 2017-001。动物实验程序均按照国家科学技术委员会发布的《实验动物管理条例》进行, 且经安徽中医药大学实验动物伦理委员会批准。

试剂及仪器 Thermo Scientific MSQ Plus液质联用质谱仪, Agilent 6120 Quadrupole液质联用质谱仪, Bruker 400 MHz超导核磁共振仪(DMSO-d₆为溶剂, TMS为内标); WRS-1B数字熔点仪(上海精密科学仪器有限公司, 温度未校正); 所用试剂均为市售分析纯; 柱色谱所用硅胶均为烟台德信生物科技有限公司产品。无糖EBSS培养基(Gibco, Grand Island, NY, USA); 青霉素(Sigma-Aldrich, St. Louis, MO); 链霉素(Sigma-Aldrich, St. Louis, MO); 胰蛋白酶(Gibco, Grand Island, NY, USA); 胎牛血清(Hyclone, Logan, UT, USA); D-Hank's液(Sigma-Aldrich, St. Louis, MO); Anti-phos-Akt antibody, Anti-Akt antibody, Anti-β-actin antibody (CST, Boston, USA); PVDF膜(0.45 μm) (Millipore, Schwalbach, Germany); 预染蛋白Marker (MBI Fermentas, Vilnius, Lithuania); 蛋白裂解液(碧云天生物技术研究所, 上海)。

1 化合物合成

1.1 苯乙烯的合成^[11](2a)

在一圆底烧瓶中, 加入甲基三苯基溴化膦(6.73 g, 18.85 mmol)、氨基钠(0.74 g, 18.85 mmol)和无水四氢呋喃(20 mL), 氮气保护, 室温反应0.5 h。取苯甲醛(2.0 g, 18.85 mmol)溶于无水四氢呋喃(10 mL), 冰浴下缓慢滴入反应液中, 滴加完毕后继续反应4 h, TLC [V (石油醚):V (乙酸乙酯)=20:1为展开剂]显示反应基本完全。将反应液过滤, 滤液减压浓缩, 经硅胶柱分离得无色油状物1.5 g, 收率76.40%。

类似方法合成化合物2b~2p。

1.2 N, N-二乙基-2-甲酰基苯甲酰胺的合成(4)

在一圆底烧瓶中, 加入邻羧基苯甲醛(10.0 g, 66.6 mmol)、氯化亚砜(25 mL)和甲苯(20 mL), 80 ℃下反应4 h, 减压浓缩, 得淡黄色油状物, 备用。在一圆底烧瓶中, 加入二乙胺(19.5 g, 266.4 mmol)和二氯甲烷(80 mL), 将制得的酰氯溶于二氯甲烷(30 mL), 冰浴条件下缓慢滴入反应液中, 滴加完毕后继续反应5 h, TLC [V (石油醚):V (乙酸乙酯)=2:1为展开剂]显示反应基本完全。向反应液中加入二氯甲烷(100 mL)稀释, 经水(2× 100 mL)、0.5 mol·L^-1盐酸(100 mL)、饱和碳酸氢钠水溶液(100 mL)和饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离得淡黄色油状物12.0 g, 收率87.78 %。

1.3 N, N-二乙基-2-(1-羟戊基)苯甲酰胺的合成(5)

在一干燥的三颈瓶中, 加入镁屑(2.13 g, 87.69 mmol)、碘(2粒)和无水四氢呋喃(40 mL), 氮气保护。取溴代正丁烷(12.0 g, 87.69 mmol)溶于无水四氢呋喃(40 mL), 缓慢滴入反应液中, 室温下搅拌, 保持反应温度不超过60 ℃, 滴加完毕后50 ℃下继续反应1 h, 将反应液降至室温后移入-20 ℃冷却液中。取N, N-二乙基-2-甲酰基苯甲酰胺(12.0 g, 58.46 mmol)溶于无水四氢呋喃(40 mL), 缓慢滴入格式试剂中, 滴加完毕后回温反应, TLC [V (石油醚):V (乙酸乙酯)=2:1为展开剂]显示反应基本完全。向反应液中滴加饱和氯化铵水溶液(80 mL), 滴加完毕后将反应液减压浓缩, 经乙酸乙酯(3× 60 mL)萃取, 合并有机相, 饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩得黄色油状物, 直接投入下一步反应。

1.4 3-丁基-异苯并呋喃-1(3H)-酮的合成(6)

在一圆底烧瓶中, 加入N, N-二乙基-2-(1-羟戊基)苯甲酰胺(粗品)、对甲苯磺酸一水合物(11.12 g, 58.46 mmol)和甲苯(50 mL), 80 ℃下反应1 h, TLC [V (石油醚):V (乙酸乙酯)=10:1为展开剂]显示反应基本完全。向反应液中加入乙酸乙酯(100 mL)稀释, 经水(2×100 mL)和饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离得淡黄色油状物8.67 g。

1.5 3-丁基-6-硝基异苯并呋喃-1(3H)-酮的合成^[12] (7)

在一圆底烧瓶中, 加入3-丁基-异苯并呋喃-1(3H)-酮(11.0 g, 57.82 mmol)和浓硫酸(50 mL), 冰浴条件下搅拌。取硝酸钾(6.43 g, 63.60 mmol)溶于浓硫酸(20 mL), 缓慢滴入反应液中, 滴加完毕后继续反应2 h, TLC [V (石油醚):V (乙酸乙酯)=10:1为展开剂]显示反应基本完全。将反应液缓慢倒入冰水(200 mL)中, 经乙酸乙酯(3×50 mL)萃取, 合并有机相, 饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩得黄色油状物, 直接投入下一步反应。

1.6 3-丁基-6-氨基异苯并呋喃-1(3H)-酮的合成(8)

在一圆底烧瓶中, 加入3-丁基-6-硝基异苯并呋喃-1(3H)-酮(粗品)、还原铁粉(12.92 g, 231.28 mmol)、氯化铵(18.56 g, 346.92 mmol)、乙醇(90 mL)和水(10 mL), 80 ℃下反应4 h, TLC [V (二氯甲烷):V (甲醇)=20:1为展开剂]显示反应基本完全。将反应液过滤, 滤饼经乙醇洗涤数次, 合并滤液, 减压浓缩。浓缩液加入二氯甲烷(100 mL)稀释, 经水(2×100 mL)和饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离得黄色固体9.0 g。

1.7 3-丁基-6-溴异苯并呋喃-1(3H)-酮的合成^[10] (9)

在一圆底烧瓶中, 加入3-丁基-6-氨基异苯并呋喃-1(3H)-酮(5.0 g, 24.36 mmol)和40%氢溴酸(30 mL)。取亚硝酸钠(1.85 g, 26.8 mmol)溶于水(5 mL), 冰浴下缓慢加入反应液中, 保持反应温度0~5 ℃, 滴加完毕后继续反应0.5 h, 备用。在一圆底烧瓶中, 加入溴化亚铜(3.5 g, 24.36 mmol)和40%氢溴酸(80 mL), 75 ℃下搅拌, 将制得的重氮盐溶液加入反应中, 继续反应2 h, TLC [V (石油醚):V (乙酸乙酯)=10:1为展开剂]显示反应基本完全。反应液降至室温后倒入分液漏斗中, 经乙酸乙酯(3×60 mL)萃取, 合并有机相, 饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离得白色固体5.2 g, 收率79.31%。

1.8 (E)-3-丁基-6-苯乙烯基异苯并呋喃-1(3H)-酮的合成^[13] (10a)

在一圆底烧瓶中, 加入3-丁基-6-溴异苯并呋喃-1(3H)-酮(0.5 g, 1.86 mmol)、苯乙烯(0.3 g, 2.88 mmol)、醋酸钯(9.0 mg, 0.04 mmol)、三(邻甲基苯基)磷(24.3 mg, 0.08 mmol)、三乙胺(0.6 g, 5.93 mmol)和N, N-二甲基甲酰胺(20 mL), 氮气保护, 100 ℃下反应4 h, TLC [V (石油醚):V (乙酸乙酯)=10:1为展开剂]显示反应基本完全。将反应液降至室温, 倒入冰水(100 mL)中, 经乙酸乙酯(3×50 mL)萃取, 合并有机相, 饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离, 无水乙醇重结晶得淡黄色固体0.42 g, 收率77.23%, mp 96.8~99.6 ℃。

类似方法合成化合物10b~10p。

1.9 (E)-3-丁基-6-(3-羟基苯乙烯基)异苯并呋喃-1(3H)-酮的合成^[14] (11a)

在一圆底烧瓶中, 加入(E)-3-丁基-6-(3-甲氧基苯乙烯基)异苯并呋喃-1(3H)-酮(1.0 g, 3.1 mmol)和二氯甲烷(20 mL), -20 ℃条件下缓慢滴加三溴化硼的二氯甲烷溶液(1 mol·L^-1, 12.4 mL), 滴加完毕后回温反应3 h, TLC [V (石油醚):V (乙酸乙酯)=2:1为展开剂]显示反应基本完全。将反应液倒入冰水(100 mL)中, 经二氯甲烷(3×50 mL)萃取, 合并有机相, 饱和氯化钠水溶液(100 mL)洗涤, 无水硫酸钠干燥, 过滤, 滤液减压浓缩, 经硅胶柱分离, 乙醇重结晶得白色固体0.68 g, 收率71.13%, mp 117.2~120.3 ℃。

类似方法合成化合物11b~11d。

2 目标化合物生物活性评价

2.1 大鼠大脑皮层神经元的原代培养

取SD大鼠乳鼠(0~1天), 左手紧握乳鼠颈肩部及四肢, 使头部固定, 常规消毒头皮后, 右手持眼科剪沿正中线剪开头皮与颅骨, 用眼科镊迅速取出整个脑组织, 放入冰上盛有D-Hank's液的玻璃培养皿中, 用镊子仔细剥离脑组织表面血管及脑膜, 再用D-Hank's液反复冲洗脑组织。用眼科剪分别剪取大鼠大脑皮质、海马体, 移入玻璃培养皿中, 剪碎大脑皮质、大鼠海马体, 再加入胰酶, 巴氏管反复吸取脑组织、海马体组织与胰酶混合物, 将两者混匀, 置于37 ℃恒温水浴箱中消化后, 加入含有血清的培养基终止消化, 然后用200目筛网过滤, 滤液离心(800 r·min^-1, 10 min), 弃去上清液, 加适量培养液悬浮沉淀, 接种于6孔塑料培养板, 置37 ℃、5% CO₂孵箱中培养。

2.2 化合物对大鼠脑皮层神经元缺氧缺糖损伤的保护

选取生长到第7天左右的细胞进行体外OGD/R模型。调节细胞密度, 以4×10⁴的细胞密度接种于48孔培养板中。使用分别含有1% FBS以及对应浓度的含药DMEM培养基, 常规培养24 h后开始制备OGD/R模型。首先将培养基更换为不含葡萄糖与血清的DMEM培养基, 同时将细胞置于含有5% CO₂、95% N₂三气培养箱中培养2 h, 完成缺氧过程; 随后将细胞培养基更换为完全DMEM培养基, 同时将细胞置于含有5% CO₂、20% O₂培养箱中培养24 h, 完成复氧过程, 孵育结束前4 h, 每孔加入MTT溶液(5 mg·mL^-1) 20 μL。孵育结束后, 弃去各孔上清液, 每孔加入DMSO 150 μL, 细胞振荡仪上振荡10 min, 待结晶物充分溶解后用酶标仪测定OD₅₇₀。通过设置模型对照组, 计算不同组别脑皮层神经元细胞存活率, 结果采用mean ± SD形式表示。数据组间统计学差异采用one-way ANOVA和Dunnett's检验, P值小于0.05认为有显著性差异。公式:存活率=(实验组OD值/空白对照组OD值)×100%。

2.3 Western blot实验

细胞复氧培养24 h后, 弃去培养基, 加入预冷4 ℃ PBS, 轻柔洗涤3次, 然后将PBS甩干后置于冰面上, 在具有PMSF的RIPA裂解缓冲液中裂解30 min, 使用BCA蛋白质测定试剂盒测定蛋白质浓度。通过10%~15% (w/v) SDS-PAGE分离蛋白质的等分试样(每泳道30 μg), 然后转移到PVDF膜上。将膜在含有5% (w/v)脱脂乳的TBST中在室温下封闭2 h, 并与p-Akt (Ser 473)、Akt和β-肌动蛋白(β-actin, 1:5 000)在4 ℃过夜。用TBST洗涤3次后, 将膜与HRP缀合的山羊抗兔IgG二抗(1:1 000)在室温下孵育1 h, 然后用TBST洗涤3次。等体积混合化学发光试剂A液和B液, 将膜蛋白面向下与此混合液充分接触; 使用Tanon 6600发光成像工作站进行检测, 并使用Image Pro Plus 6.0软件对光密度值进行分析, 将待测蛋白水平与内参照β-actin/非磷酸化蛋白水平进行对比, 表示蛋白相对表达水平/磷酸化水平。

基金

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安徽省自然科学基金资助项目(1508085MB3)

参考文献

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文献

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参考文献引证文献

排序方式：

[1]

Ayuso

, Gonzalo-Gobernado

, Montaner

. Neuroprotective diets for stroke[J]. Neurochem Int, 2017, 107: 4-10.

https://doi.org/10.1016/j.neuint.2017.01.013

[2]

Sifat

, Vaidya

, Abbruscato

. Blood-brain barrier protection as a therapeutic strategy for acute ischemic stroke[J]. AAPS J, 2017, 19: 957-972.

https://doi.org/10.1208/s12248-017-0091-7

[3]

Vaidya

, Sifat

, Karamyan

et al . The neuroprotective role of the brain opioid system in stroke injury[J]. Drug Discov Today, 2018, 23: 1385-1395.

https://doi.org/10.1016/j.drudis.2018.02.011

[4]

Bastianetto

, Menard

, Quirion

. Neuroprotective action of resveratrol[J]. Biochim Biophys Acta, 2015, 1852: 1195-1201.

https://doi.org/10.1016/j.bbadis.2014.09.011

[5]

Chao

, Li

, Cheng

et al . Protective effects of pinostilbene, a resveratrol methylated derivative, against 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells[J]. J Nutr Biochem, 2010, 21: 482-489.

https://doi.org/10.1016/j.jnutbio.2009.02.004

[6]

Chang

, Rimando

, Pallas

et al . Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease[J]. Neurobiol Aging, 2012, 33: 2062-2071.

https://doi.org/10.1016/j.neurobiolaging.2011.08.015

[7]

Yin

, Lan

, Huang

et al . Discovery of a ring-opened derivative of 3-n-butylphthalide bearing NO/H₂S-donating moieties as a potential anti-ischemic stroke agent[J]. Eur J Med Chem, 2016, 115: 369-380.

https://doi.org/10.1016/j.ejmech.2016.03.044

[8]

Barta-Szalai

, Borza

, Bozó

et al . Oxamides as novel NR2B selective NMDA receptor antagonists[J]. Bioorg Med Chem Lett, 2004, 14: 3953-3956.

https://doi.org/10.1016/j.bmcl.2004.05.053

[9]

Wang

, Wang

, Li

et al . Novel hybrids of optically active ring-opened 3-n-butylphthalide derivative and isosorbide as potential anti-ischemic stroke agents[J]. J Med Chem, 2013, 56: 3078-3089.

https://doi.org/10.1021/jm4001693

[10]

Wang

, Cha

, Reiner

et al . Synthesis and biological activity of n-butylphthalide derivatives[J]. Eur J Med Chem, 2010, 45: 1941-1946.

https://doi.org/10.1016/j.ejmech.2010.01.036

[11]

Sun

, Hoshino

, Jermihov

et al . Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer[J]. Bioorg Med Chem, 2010, 18: 5352-5366.

https://doi.org/10.1016/j.bmc.2010.05.042

[12]

Wang

, Wang

, Huang

et al . Synthesis and biological evaluation of nitric oxide releasing derivatives of 6-amino-3-n-butylphthalide as potential antiplatelet agents[J]. Bioorg Med Chem Lett, 2013, 23: 1985-1988.

https://doi.org/10.1016/j.bmcl.2013.02.035

[13]

Nobre

, Muniz

, Seferin

et al . The synthesis of non-symmetrical stilbene analogs of trans-resveratrol using the same Pd catalyst in a sequential double-Heck arylation of ethylene[J]. Appl Org Chem, 2011, 25: 289-293.

https://doi.org/10.1002/aoc.1756

[14]

Uzura

, Sekine-Suzuki

, Nakanishi

et al . A facile and rapid access to resveratrol derivatives and their radioprotective activity[J]. Bioorg Med Chem Lett, 2016, 26: 3886-3891.

https://doi.org/10.1016/j.bmcl.2016.07.018

2019年第54卷第8期

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doi: 10.16438/j.0513-4870.2019-0364

接收时间：2019-05-13
首发时间：2026-01-26
出版时间：2019-08-12

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收稿日期：2019-05-13
修回日期：2019-06-10

基金

安徽省自然科学基金资助项目(1508085MB3)

作者信息

1.合肥工业大学食品与生物工程学院, 安徽合肥 230009

2.安徽中医药大学药学院, 安徽合肥 230012

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*阮班锋, Tel/Fax:86-551-62901534, E-mail:ruanbf@hfut.edu.cn

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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10a	H	H	H	H	77.23	97-99	Light yellow solid
10b	H	CH₃	H	H	56.15	114-116	Light yellow solid
10c	H	H	CH₃	H	61.41	114-116	Light yellow solid
10d	OCH₃	H	H	H	88.38	-	Yellow oil
10e	H	OCH₃	H	H	65.04	82-84	White solid
10f	H	H	OCH₃	H	80.04	106-108	Light yellow solid
10g	H	OCH₃	OCH₃	H	62.55	139-141	Light yellow solid
10h	H	OCH₃	H	OCH₃	67.12	112-114	White solid
10i	H	OCH₃	OCH₃	OCH₃	61.85	142-144	White solid
10j	H	H	OAc	H	50.63	122-123	White solid
10k	H	F	H	H	69.29	96-98	White solid
10l	H	H	F	H	72.75	105-107	Light yellow solid
10m	H	Cl	H	H	52.64	115-116	White solid
10n	H	H	Cl	H	57.58	137-139	Light yellow solid
10o	H	H	NO₂	H	62.15	134-136	Yellow solid
10p	H	H	CF₃	H	52.21	134-136	White solid
11a	H	OH	H	H	71.13	117-120	White solid
11b	H	H	OH	H	62.76	192-193	Light yellow solid
11c	H	OH	OH	H	59.78	201-202	Light yellow solid
11d	H	OH	H	OH	56.52	177-180	Light yellow solid

Compd.

R₁

R₂

R₃

R₄

Yield%

mp/℃

Character

10a

77.23

97-99

Light yellow solid

10b

CH₃

56.15

114-116

Light yellow solid

10c

CH₃

61.41

114-116

Light yellow solid

10d

OCH₃

88.38

Yellow oil

10e

OCH₃

65.04

82-84

White solid

10f

OCH₃

80.04

106-108

Light yellow solid

10g

OCH₃

62.55

139-141

Light yellow solid

10h

OCH₃

67.12

112-114

White solid

10i

OCH₃

61.85

142-144

White solid

10j

OAc

50.63

122-123

White solid

10k

69.29

96-98

White solid

10l

72.75

105-107

Light yellow solid

10m

52.64

115-116

White solid

10n

57.58

137-139

Light yellow solid

10o

NO₂

62.15

134-136

Yellow solid

10p

CF₃

52.21

134-136

White solid

11a

71.13

117-120

White solid

11b

62.76

192-193

Light yellow solid

11c

59.78

201-202

Light yellow solid

11d

56.52

177-180

Light yellow solid

Compd.	¹H NMR, ¹³C NMR, ESI-MS
10a	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.65 (d, J = 7.2 Hz, 2H, Ar-H), 7.51-7.36 (m, 4H), 7.31 (d, J = 7.2 Hz, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.02 (m, 1H, CH₂a), 1.77-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.54, 138.95, 137.15, 132.89, 130.71, 129.20, 128.49, 127.35, 127.17, 126.57, 123.32, 122.62, 81.59, 33.99, 26.93, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₂: m/z 293.34 [M+H]⁺.
10b	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.49-7.36 (m, 4H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 7.6 Hz, 1H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.34 (s, 3H, Ar-CH₃), 2.12-2.00 (m, 1H, CH₂a), 1.77-1.63 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 149.49, 139.02, 138.25, 137.08, 132.84, 130.79, 129.21, 129.07, 127.65, 127.18, 126.57, 124.48, 123.31, 122.56, 81.57, 34.00, 26.92, 22.35, 21.48, 14.25; ESI-MS for C₂₁H₂₂O₂: m/z 307.22 [M+H]⁺.
10c	¹H NMR (400 MHz, DMSO-d₆) δ: 8.01 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (d, J = 8.0 Hz, 2H, Ar-H), 7.41 (d, J = 16.4 Hz, 1H, =CH), 7.33 (d, J = 16.4 Hz, 1H, =CH), 7.21 (d, J = 8.0 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.32 (s, 3H, Ar-CH₃), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.32, 139.10, 137.95, 134.37, 132.73, 130.62, 129.78, 127.11, 126.54, 126.31, 123.25, 122.43, 81.56, 34.02, 26.95, 22.36, 21.33, 14.26; ESI-MS for C₂₁H₂₂O₂: m/z 307.14 [M+H]⁺.
10d	¹H NMR (400 MHz, DMSO-d₆) δ: 7.98 (d, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.70-7.64 (m, 2H, Ar-H), 7.55 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.34-7.26 (m, 1H, Ar-H), 7.06 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (t, J = 8.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 3.88 (s, 3H, Ar-OCH₃), 2.11-2.02 (m, 1H, CH₂a), 1.76-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.24, 157.18, 149.39, 139.34, 132.58, 129.83, 127.79, 127.10, 126.55, 125.46, 125.27, 123.29, 122.48, 121.04, 111.84, 81.56, 55.91, 34.01, 26.94, 22.36, 14.24; ESI-MS for C₂₁H₂₂O₃: m/z 323.11 [M+H]⁺.
10e	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.43 (s, 2H, =CH×2), 7.32 (t, J = 8.0 Hz, 1H, Ar-H), 7.25-7.20 (m, 2H, Ar-H), 6.92-6.86 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.81 (s, 3H, Ar-OCH₃), 2.14-2.01 (m, 1H, CH₂a), 1.79-1.66 (m, 1H, CH₂b), 1.45-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.27, 160.04, 149.56, 138.90, 138.60, 132.88, 130.63, 130.18, 127.64, 126.56, 123.32, 122.62, 119.75, 114.26, 112.23, 81.59, 55.51, 33.98, 26.95, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 322.92 [M+H]⁺.
10f	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (d, J = 8.8 Hz, 2H, Ar-H), 7.40 (d, J = 16.4 Hz, 1H, =CH), 7.24 (d, J = 16.4 Hz, 1H, =CH), 6.97 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.79 (s, 3H, Ar-OCH₃), 2.14-2.00 (m, 1H, CH₂a), 1.78-1.63 (m, 1H, CH₂b), 1.42-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 159.73, 149.08, 139.34, 132.60, 130.37, 129.76, 128.54, 126.52, 124.99, 123.25, 122.17, 114.65, 81.57, 55.61, 34.00, 26.94, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 323.16 [M+H]⁺.
10g	¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.96 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.32-7.26 (m, 2H), 7.15 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 3H, Ar-OCH₃), 3.78 (s, 3H, Ar-OCH₃), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 149.51, 149.37, 149.05, 139.35, 132.53, 130.72, 130.05, 126.53, 125.12, 123.24, 122.12, 120.78, 112.09, 109.74, 81.58, 55.90, 34.04, 26.99, 22.36, 14.25; ESI-MS for C₂₂H₂₄O₄: m/z 353.10 [M+H]⁺.
10h	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.44 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 6.83 (d, J = 2.4 Hz, 2H, Ar-H), 6.46 (t, J = 2.4 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.80 (s, 6H, Ar-OCH₃), 2.13-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.45-1.21 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 161.12, 149.56, 139.15, 138.85, 132.84, 130.70, 127.84, 126.56, 123.27, 122.63, 105.17, 100.62, 81.59, 55.63, 34.02, 26.99, 22.36, 14.24; ESI-MS for C₂₂H₂₄O₄: m/z 353.23 [M+H]⁺; HR-MS (ESI⁺) [M+H]⁺: m/z Calcd. for C₂₂H₂₄O₄: 353.174 7; Found: 353.174 5.
10i	¹H NMR (400 MHz, DMSO-d₆) δ: 8.02 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.40 (s, 2H, Ar-H), 6.99 (s, 2H, =CH×2), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 6H, Ar-OCH₃), 3.69 (s, 3H, Ar-OCH₃), 2.12-2.01 (m, 1H, CH₂a), 1.76-1.65 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 153.52, 149.32, 139.09, 138.06, 132.87, 132.68, 130.85, 126.65, 126.57, 123.31, 122.30, 104.56, 81.60, 60.52, 56.28, 34.03, 26.99, 22.36, 14.24; ESI-MS for C₂₃H₂₆O₅: m/z 383.06 [M+H]⁺; HR-MS (ESI⁺) [M+Na]⁺: m/z Calcd. for C₂₃H₂₆O₅: 405.167 2; Found: 405.167 0.
10j	¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.71-7.65 (m, 3H, Ar-H), 7.48 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 8.8 Hz, Ar-H), 5.65 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.29 (s, 3H, COCH₃), 2.14-2.02 (m, 1H, CH₂a), 1.78-1.66 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 169.64, 150.64, 149.58, 138.90, 134.87, 132.92, 129.79, 128.14, 127.49, 126.57, 123.35, 122.64, 81.60, 33.97, 26.92, 22.36, 21.33, 14.27; ESI-MS for C₂₂H₂₂O₄: m/z 351.09 [M+H]⁺.
10k	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.55-7.40 (m, 5H), 7.17-7.09 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ:170.21, 163.05 (J_C-F = 241.9 Hz), 149.84, 139.86 (J_C-F = 7.8 Hz), 138.57, 133.06, 131.07 (J_C-F = 8.6 Hz), 129.45 (J_C-F = 2.7 Hz), 128.92, 126.58, 123.60 (J_C-F = 2.7 Hz), 123.37, 122.76, 115.09 (J_C-F = 21.1 Hz), 113.14 (J_C-F = 21.8 Hz), 81.61, 33.96, 26.93, 22.35, 14.25; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10l	¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73-7.64 (m, 3H, Ar-H), 7.47 (d, J = 16.4 Hz, 1H, =CH), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.29-7.20 (m, 2H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 162.34 (J_C-F = 244.1 Hz), 149.50, 138.88, 133.75 (J_C-F = 3.0 Hz), 132.85, 129.52, 129.06 (J_C-F = 8.0 Hz), 127.23 (J_C-F = 2.4 Hz), 126.55, 122.90 (J_C-F = 77.2 Hz), 116.18, 115.97, 81.58, 33.99, 26.93, 22.35, 14.23; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.
10m	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73 (t, J = 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.59 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 16.4 Hz, 1H, =CH), 7.48-7.39 (m, 2H), 7.38-7.32 (m, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.21, 149.86, 139.50, 138.56, 134.07, 133.08, 130.97, 129.15, 129.04, 128.08, 126.57, 125.87, 123.36, 122.80, 81.60, 33.97, 26.94, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.8 [M+H]⁺.
10n	¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.72-7.63 (m, 3H, Ar-H), 7.51-7.38 (m, 4H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.23, 149.69, 138.69, 136.11, 132.99, 132.80, 129.35, 129.18, 128.77, 128.18, 126.57, 123.31, 122.69, 81.60, 33.98, 26.95, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.9 [M+H]⁺.
10o	¹H NMR (400 MHz, DMSO-d₆) δ: 8.24 (d, J = 8.8 Hz, 2H, Ar-H), 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.87 (d, J = 8.8 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.66 (d, J = 16.4 Hz, 1H, =CH), 7.61 (d, J = 16.4 Hz, 1H, =CH), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.10, 150.40, 146.81, 144.03, 138.13, 133.44, 132.01, 128.55, 127.94, 126.63, 124.45, 123.44, 123.27, 81.64, 33.93, 26.98, 22.35, 14.24; ESI-MS for C₂₀H₁₉NO₄: m/z 337.9 [M+H]⁺.
10p	¹H NMR (400 MHz, DMSO-d₆) δ: 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.85 (d, J = 8.4 Hz, 2H, Ar-H), 7.76 (d, J = 8.4 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (s, 2H, =CH×2), 5.66 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.02 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.17, 150.07, 141.27, 138.38, 133.22, 130.20, 129.11, 128.32 (J_C-F = 31.6 Hz), 127.63, 126.60, 126.02 (J_C-F = 3.9 Hz), 124.74 (J_C-F = 269.8 Hz), 123.37, 123.03, 81.60, 33.96, 26.95, 22.34, 14.21; ESI-MS for C₂₁H₁₉F₃O₂: m/z 360.9 [M+H]⁺.
11a	¹H NMR (400 MHz, DMSO-d₆) δ: 9.48 (s, 1H, Ar-OH), 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.37 (d, J = 16.4 Hz, 1H, =CH), 7.30 (d, J = 16.4 Hz, 1H, =CH), 7.19 (t, J = 8.0 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 7.02 (t, J = 2.0 Hz, 1H, Ar-H), 6.72 (dd, J = 8.0, 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.00 (m, 1H, CH₂a), 1.78- 1.64 (m, 1H, CH₂b), 1.44-1.21 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 158.13, 149.46, 138.95, 138.46, 132.85, 130.93, 130.10, 127.12, 126.54, 123.22, 122.65, 118.18, 115.72, 113.81, 81.56, 34.01, 26.94, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₃: m/z 309.04 [M+H]⁺.
11b	¹H NMR (400 MHz, DMSO-d₆) δ: 9.68 (s, 1H, Ar-OH), 8.00-7.92 (m, 2H, Ar-H), 7.64 (d, J = 8.0 Hz, 1H, Ar-H), 7.47 (d, J = 8.8 Hz, 2H, Ar-H), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 16.4 Hz, 1H, =CH), 6.80 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.37, 158.16, 148.88, 139.51, 132.47, 130.77, 128.66, 128.18, 126.50, 123.97, 123.20, 122.02, 116.06, 81.56, 34.03, 26.94, 22.37, 14.27; ESI-MS for C₂₀H₂₀O₃: m/z 309.23 [M+H]⁺.
11c	¹H NMR (400 MHz, DMSO-d₆) δ: 9.19 (s, 1H, Ar-OH), 8.99 (s, 1H, Ar-OH), 7.98-7.92 (m, 2H, Ar-H), 7.62 (d, J = 8.0 Hz, 1H, Ar-H), 7.26 (d, J = 16.4 Hz, 1H, =CH), 7.07 (d, J = 16.4 Hz, 1H, =CH), 6.92 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.76 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.38, 148.84, 146.49, 145.91, 139.52, 132.48, 131.17, 128.75, 126.48, 123.88, 123.17, 122.06, 119.45, 116.17, 114.05, 81.54, 34.02, 26.92, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₄: m/z 325.39 [M+H]⁺.
11d	¹H NMR (400 MHz, DMSO-d₆) δ: 9.30 (s, 2H, Ar-OH), 8.02 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.27 (d, J = 16.4 Hz, 1H, =CH), 7.19 (d, J = 16.4 Hz, 1H, =CH), 6.49 (d, J = 2.0 Hz, 2H, Ar-H), 6.20 (t, J = 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.29, 159.04, 149.40, 138.97, 138.88, 132.84, 131.29, 126.84, 126.51, 123.19, 122.66, 105.44, 103.21, 81.55, 34.00, 26.92, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₄: m/z 325.16 [M+H]⁺.

Compd.

¹H NMR, ¹³C NMR, ESI-MS

10a

¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.65 (d, J = 7.2 Hz, 2H, Ar-H), 7.51-7.36 (m, 4H), 7.31 (d, J = 7.2 Hz, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.02 (m, 1H, CH₂a), 1.77-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.54, 138.95, 137.15, 132.89, 130.71, 129.20, 128.49, 127.35, 127.17, 126.57, 123.32, 122.62, 81.59, 33.99, 26.93, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₂: m/z 293.34 [M+H]⁺.

10b

¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.49-7.36 (m, 4H), 7.28 (t, J = 7.6 Hz, 1H, Ar-H), 7.12 (d, J = 7.6 Hz, 1H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.34 (s, 3H, Ar-CH₃), 2.12-2.00 (m, 1H, CH₂a), 1.77-1.63 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 149.49, 139.02, 138.25, 137.08, 132.84, 130.79, 129.21, 129.07, 127.65, 127.18, 126.57, 124.48, 123.31, 122.56, 81.57, 34.00, 26.92, 22.35, 21.48, 14.25; ESI-MS for C₂₁H₂₂O₂: m/z 307.22 [M+H]⁺.

10c

¹H NMR (400 MHz, DMSO-d₆) δ: 8.01 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.53 (d, J = 8.0 Hz, 2H, Ar-H), 7.41 (d, J = 16.4 Hz, 1H, =CH), 7.33 (d, J = 16.4 Hz, 1H, =CH), 7.21 (d, J = 8.0 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.32 (s, 3H, Ar-CH₃), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 149.32, 139.10, 137.95, 134.37, 132.73, 130.62, 129.78, 127.11, 126.54, 126.31, 123.25, 122.43, 81.56, 34.02, 26.95, 22.36, 21.33, 14.26; ESI-MS for C₂₁H₂₂O₂: m/z 307.14 [M+H]⁺.

10d

¹H NMR (400 MHz, DMSO-d₆) δ: 7.98 (d, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.95 (s, 1H, Ar-H), 7.70-7.64 (m, 2H, Ar-H), 7.55 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.34-7.26 (m, 1H, Ar-H), 7.06 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (t, J = 8.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 3.88 (s, 3H, Ar-OCH₃), 2.11-2.02 (m, 1H, CH₂a), 1.76-1.66 (m, 1H, CH₂b), 1.42-1.24 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.24, 157.18, 149.39, 139.34, 132.58, 129.83, 127.79, 127.10, 126.55, 125.46, 125.27, 123.29, 122.48, 121.04, 111.84, 81.56, 55.91, 34.01, 26.94, 22.36, 14.24; ESI-MS for C₂₁H₂₂O₃: m/z 323.11 [M+H]⁺.

10e

¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.43 (s, 2H, =CH×2), 7.32 (t, J = 8.0 Hz, 1H, Ar-H), 7.25-7.20 (m, 2H, Ar-H), 6.92-6.86 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.81 (s, 3H, Ar-OCH₃), 2.14-2.01 (m, 1H, CH₂a), 1.79-1.66 (m, 1H, CH₂b), 1.45-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.27, 160.04, 149.56, 138.90, 138.60, 132.88, 130.63, 130.18, 127.64, 126.56, 123.32, 122.62, 119.75, 114.26, 112.23, 81.59, 55.51, 33.98, 26.95, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 322.92 [M+H]⁺.

10f

¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (d, J = 8.8 Hz, 2H, Ar-H), 7.40 (d, J = 16.4 Hz, 1H, =CH), 7.24 (d, J = 16.4 Hz, 1H, =CH), 6.97 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.79 (s, 3H, Ar-OCH₃), 2.14-2.00 (m, 1H, CH₂a), 1.78-1.63 (m, 1H, CH₂b), 1.42-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 159.73, 149.08, 139.34, 132.60, 130.37, 129.76, 128.54, 126.52, 124.99, 123.25, 122.17, 114.65, 81.57, 55.61, 34.00, 26.94, 22.36, 14.27; ESI-MS for C₂₁H₂₂O₃: m/z 323.16 [M+H]⁺.

10g

¹H NMR (400 MHz, DMSO-d₆) δ: 7.99 (s, 1H, Ar-H), 7.96 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.32-7.26 (m, 2H), 7.15 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.97 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 3H, Ar-OCH₃), 3.78 (s, 3H, Ar-OCH₃), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.34, 149.51, 149.37, 149.05, 139.35, 132.53, 130.72, 130.05, 126.53, 125.12, 123.24, 122.12, 120.78, 112.09, 109.74, 81.58, 55.90, 34.04, 26.99, 22.36, 14.25; ESI-MS for C₂₂H₂₄O₄: m/z 353.10 [M+H]⁺.

10h

¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.67 (d, J = 8.0 Hz, 1H, Ar-H), 7.44 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 6.83 (d, J = 2.4 Hz, 2H, Ar-H), 6.46 (t, J = 2.4 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.80 (s, 6H, Ar-OCH₃), 2.13-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.45-1.21 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 161.12, 149.56, 139.15, 138.85, 132.84, 130.70, 127.84, 126.56, 123.27, 122.63, 105.17, 100.62, 81.59, 55.63, 34.02, 26.99, 22.36, 14.24; ESI-MS for C₂₂H₂₄O₄: m/z 353.23 [M+H]⁺; HR-MS (ESI⁺) [M+H]⁺: m/z Calcd. for C₂₂H₂₄O₄: 353.174 7; Found: 353.174 5.

10i

¹H NMR (400 MHz, DMSO-d₆) δ: 8.02 (s, 1H, Ar-H), 7.97 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.68 (d, J = 8.0 Hz, 1H, Ar-H), 7.40 (s, 2H, Ar-H), 6.99 (s, 2H, =CH×2), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 3.84 (s, 6H, Ar-OCH₃), 3.69 (s, 3H, Ar-OCH₃), 2.12-2.01 (m, 1H, CH₂a), 1.76-1.65 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 153.52, 149.32, 139.09, 138.06, 132.87, 132.68, 130.85, 126.65, 126.57, 123.31, 122.30, 104.56, 81.60, 60.52, 56.28, 34.03, 26.99, 22.36, 14.24; ESI-MS for C₂₃H₂₆O₅: m/z 383.06 [M+H]⁺; HR-MS (ESI⁺) [M+Na]⁺: m/z Calcd. for C₂₃H₂₆O₅: 405.167 2; Found: 405.167 0.

10j

¹H NMR (400 MHz, DMSO-d₆) δ: 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.71-7.65 (m, 3H, Ar-H), 7.48 (d, J = 16.4 Hz, 1H, =CH), 7.38 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 8.8 Hz, Ar-H), 5.65 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.29 (s, 3H, COCH₃), 2.14-2.02 (m, 1H, CH₂a), 1.78-1.66 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.88 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 169.64, 150.64, 149.58, 138.90, 134.87, 132.92, 129.79, 128.14, 127.49, 126.57, 123.35, 122.64, 81.60, 33.97, 26.92, 22.36, 21.33, 14.27; ESI-MS for C₂₂H₂₂O₄: m/z 351.09 [M+H]⁺.

10k

¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.55-7.40 (m, 5H), 7.17-7.09 (m, 1H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.43-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ:170.21, 163.05 (J_C-F = 241.9 Hz), 149.84, 139.86 (J_C-F = 7.8 Hz), 138.57, 133.06, 131.07 (J_C-F = 8.6 Hz), 129.45 (J_C-F = 2.7 Hz), 128.92, 126.58, 123.60 (J_C-F = 2.7 Hz), 123.37, 122.76, 115.09 (J_C-F = 21.1 Hz), 113.14 (J_C-F = 21.8 Hz), 81.61, 33.96, 26.93, 22.35, 14.25; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.

10l

¹H NMR (400 MHz, DMSO-d₆) δ: 8.03 (s, 1H, Ar-H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73-7.64 (m, 3H, Ar-H), 7.47 (d, J = 16.4 Hz, 1H, =CH), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.29-7.20 (m, 2H, Ar-H), 5.64 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.78-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.26, 162.34 (J_C-F = 244.1 Hz), 149.50, 138.88, 133.75 (J_C-F = 3.0 Hz), 132.85, 129.52, 129.06 (J_C-F = 8.0 Hz), 127.23 (J_C-F = 2.4 Hz), 126.55, 122.90 (J_C-F = 77.2 Hz), 116.18, 115.97, 81.58, 33.99, 26.93, 22.35, 14.23; ESI-MS for C₂₀H₁₉FO₂: m/z 310.9 [M+H]⁺.

10m

¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.73 (t, J = 1.6 Hz, 1H, Ar-H), 7.69 (d, J = 8.0 Hz, 1H, Ar-H), 7.59 (d, J = 7.6 Hz, 1H, Ar-H), 7.51 (d, J = 16.4 Hz, 1H, =CH), 7.48-7.39 (m, 2H), 7.38-7.32 (m, 1H, Ar-H), 5.65 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.14-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.21, 149.86, 139.50, 138.56, 134.07, 133.08, 130.97, 129.15, 129.04, 128.08, 126.57, 125.87, 123.36, 122.80, 81.60, 33.97, 26.94, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.8 [M+H]⁺.

10n

¹H NMR (400 MHz, DMSO-d₆) δ: 8.05 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.72-7.63 (m, 3H, Ar-H), 7.51-7.38 (m, 4H, Ar-H), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.23, 149.69, 138.69, 136.11, 132.99, 132.80, 129.35, 129.18, 128.77, 128.18, 126.57, 123.31, 122.69, 81.60, 33.98, 26.95, 22.36, 14.26; ESI-MS for C₂₀H₁₉ClO₂: m/z 326.9 [M+H]⁺.

10o

¹H NMR (400 MHz, DMSO-d₆) δ: 8.24 (d, J = 8.8 Hz, 2H, Ar-H), 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.87 (d, J = 8.8 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.66 (d, J = 16.4 Hz, 1H, =CH), 7.61 (d, J = 16.4 Hz, 1H, =CH), 5.65 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.43-1.22 (m, 4H, CH₂×2), 0.86 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.10, 150.40, 146.81, 144.03, 138.13, 133.44, 132.01, 128.55, 127.94, 126.63, 124.45, 123.44, 123.27, 81.64, 33.93, 26.98, 22.35, 14.24; ESI-MS for C₂₀H₁₉NO₄: m/z 337.9 [M+H]⁺.

10p

¹H NMR (400 MHz, DMSO-d₆) δ: 8.11 (s, 1H, Ar-H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.85 (d, J = 8.4 Hz, 2H, Ar-H), 7.76 (d, J = 8.4 Hz, 2H, Ar-H), 7.71 (d, J = 8.0 Hz, 1H, Ar-H), 7.58 (s, 2H, =CH×2), 5.66 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.02 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.22 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.17, 150.07, 141.27, 138.38, 133.22, 130.20, 129.11, 128.32 (J_C-F = 31.6 Hz), 127.63, 126.60, 126.02 (J_C-F = 3.9 Hz), 124.74 (J_C-F = 269.8 Hz), 123.37, 123.03, 81.60, 33.96, 26.95, 22.34, 14.21; ESI-MS for C₂₁H₁₉F₃O₂: m/z 360.9 [M+H]⁺.

11a

¹H NMR (400 MHz, DMSO-d₆) δ: 9.48 (s, 1H, Ar-OH), 8.04 (s, 1H, Ar-H), 8.01 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.66 (d, J = 8.0 Hz, 1H, Ar-H), 7.37 (d, J = 16.4 Hz, 1H, =CH), 7.30 (d, J = 16.4 Hz, 1H, =CH), 7.19 (t, J = 8.0 Hz, 1H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 7.02 (t, J = 2.0 Hz, 1H, Ar-H), 6.72 (dd, J = 8.0, 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 8.0, 4.0 Hz, 1H, CH), 2.14-2.00 (m, 1H, CH₂a), 1.78- 1.64 (m, 1H, CH₂b), 1.44-1.21 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.28, 158.13, 149.46, 138.95, 138.46, 132.85, 130.93, 130.10, 127.12, 126.54, 123.22, 122.65, 118.18, 115.72, 113.81, 81.56, 34.01, 26.94, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₃: m/z 309.04 [M+H]⁺.

11b

¹H NMR (400 MHz, DMSO-d₆) δ: 9.68 (s, 1H, Ar-OH), 8.00-7.92 (m, 2H, Ar-H), 7.64 (d, J = 8.0 Hz, 1H, Ar-H), 7.47 (d, J = 8.8 Hz, 2H, Ar-H), 7.35 (d, J = 16.4 Hz, 1H, =CH), 7.17 (d, J = 16.4 Hz, 1H, =CH), 6.80 (d, J = 8.8 Hz, 2H, Ar-H), 5.63 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.64 (m, 1H, CH₂b), 1.43-1.23 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.37, 158.16, 148.88, 139.51, 132.47, 130.77, 128.66, 128.18, 126.50, 123.97, 123.20, 122.02, 116.06, 81.56, 34.03, 26.94, 22.37, 14.27; ESI-MS for C₂₀H₂₀O₃: m/z 309.23 [M+H]⁺.

11c

¹H NMR (400 MHz, DMSO-d₆) δ: 9.19 (s, 1H, Ar-OH), 8.99 (s, 1H, Ar-OH), 7.98-7.92 (m, 2H, Ar-H), 7.62 (d, J = 8.0 Hz, 1H, Ar-H), 7.26 (d, J = 16.4 Hz, 1H, =CH), 7.07 (d, J = 16.4 Hz, 1H, =CH), 6.92 (dd, J = 8.4, 2.0 Hz, 1H, Ar-H), 6.76 (d, J = 8.4 Hz, 1H, Ar-H), 5.62 (dd, J = 7.6, 4.0 Hz, 1H, CH), 2.12-2.00 (m, 1H, CH₂a), 1.76-1.64 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.38, 148.84, 146.49, 145.91, 139.52, 132.48, 131.17, 128.75, 126.48, 123.88, 123.17, 122.06, 119.45, 116.17, 114.05, 81.54, 34.02, 26.92, 22.36, 14.27; ESI-MS for C₂₀H₂₀O₄: m/z 325.39 [M+H]⁺.

11d

¹H NMR (400 MHz, DMSO-d₆) δ: 9.30 (s, 2H, Ar-OH), 8.02 (s, 1H, Ar-H), 8.00 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.65 (d, J = 8.0 Hz, 1H, Ar-H), 7.27 (d, J = 16.4 Hz, 1H, =CH), 7.19 (d, J = 16.4 Hz, 1H, =CH), 6.49 (d, J = 2.0 Hz, 2H, Ar-H), 6.20 (t, J = 2.0 Hz, 1H, Ar-H), 5.64 (dd, J = 7.6, 3.6 Hz, 1H, CH), 2.13-2.01 (m, 1H, CH₂a), 1.77-1.65 (m, 1H, CH₂b), 1.44-1.20 (m, 4H, CH₂×2), 0.87 (t, J = 7.2 Hz, 3H, CH₃); ¹³C NMR (100 MHz, DMSO-d₆) δ: 170.29, 159.04, 149.40, 138.97, 138.88, 132.84, 131.29, 126.84, 126.51, 123.19, 122.66, 105.44, 103.21, 81.55, 34.00, 26.92, 22.36, 14.25; ESI-MS for C₂₀H₂₀O₄: m/z 325.16 [M+H]⁺.

Compd.	Survival rate ± SD
NBP	58.87 ± 1.44	64.63 ± 2.13^**	72.12 ± 1.52^**	87.17 ± 1.24^**
Resveratrol	58.76 ± 1.59	63.22 ± 2.33^**	67.44 ± 2.41^**	79.86 ± 1.93^**
10a	60.00 ± 1.03	64.53 ± 0.78^**	72.38 ± 1.52^**^△△	85.15 ± 1.83^**^△△
10b	59.03 ± 1.77	62.77 ± 2.45^**	67.62 ± 1.59^**##	79.59 ± 1.05^**##
10c	59.67 ± 1.88	63.04 ± 1.45^**	69.68 ± 1.37^**	79.84 ± 1.45^**##
10d	58.57 ± 1.01	59.50 ± 0.98^##^△△	64.64 ± 1.22^**##	66.96 ± 1.41^**##^△△
10e	58.19 ± 1.06	59.61 ± 1.22^##^△	64.64 ± 0.81^**##	66.90 ± 0.64^**##^△△
10f	59.77 ± 2.63	60.83 ± 2.70^##	65.54 ± 2.30^**##	68.49 ± 2.40^**##^△△
10g	58.60 ± 2.89	65.42 ± 0.95^**	72.07 ± 2.70^**^△△	86.36 ± 2.14^**^△△
10h	59.62 ± 0.55	68.59 ± 1.16^**##^△△	79.64 ± 1.84^**##^△△	85.64 ± 0.90^**^△△
10i	58.59 ± 1.03	72.83 ± 1.64^**##^△△	81.75 ± 1.07^**##^△△	88.34 ± 1.34^**^△△
10j	58.77 ± 2.31	67.61 ± 1.43^**^△△	75.36 ± 2.58^**#^△△	81.99 ± 2.69^**##
10k	59.11 ± 1.30	60.14 ± 1.17^##	61.73 ± 2.25^*##^△△	63.41 ± 1.77^**##^△△
10l	59.77 ± 2.03	61.45 ± 2.24^#	62.44 ± 2.22^*##^△△	63.26 ± 2.84^**##^△△
10m	58.75 ± 0.76	59.32 ± 1.48^##^△△	62.37 ± 2.36^**##^△△	64.91 ± 1.71^**##^△△
10n	60.72 ± 1.63	62.13 ± 2.01	63.33 ± 1.89^*##^△△	64.62 ± 1.83^**##^△△
10o	58.30 ± 1.81	59.84 ± 0.68^##^△	62.74 ± 1.95^**##^△△	64.94 ± 1.68^**##^△△
10p	57.90 ± 1.00	67.60 ± 1.65^**^△△	73.79 ± 1.14^**^△△	79.51 ± 1.46^**##
11a	59.56 ± 1.47	66.76 ± 0.51^**^△	72.01 ± 1.33^**^△△	79.99 ± 1.88^**##
11b	59.00 ± 0.69	61.91 ± 0.96^*	68.82 ± 1.37^**#	77.72 ± 1.76^**##
11c	58.36 ± 1.30	61.50 ± 1.96^*	69.72 ± 2.10^**	78.29 ± 1.32^**##
11d	58.68 ± 1.10	62.30 ± 0.94^**	69.40 ± 1.71^**	77.64 ± 0.32^**##

Compd.

Survival rate ± SD

OGD/R

0.1 μmol·L^-1

1 μmol·L^-1

10 μmol·L^-1

NBP

58.87 ± 1.44

64.63 ± 2.13^**

72.12 ± 1.52^**

87.17 ± 1.24^**

Resveratrol

58.76 ± 1.59

63.22 ± 2.33^**

67.44 ± 2.41^**

79.86 ± 1.93^**

10a

60.00 ± 1.03

64.53 ± 0.78^**

72.38 ± 1.52^**^△△

85.15 ± 1.83^**^△△

10b

59.03 ± 1.77

62.77 ± 2.45^**

67.62 ± 1.59^**##

79.59 ± 1.05^**##

10c

59.67 ± 1.88

63.04 ± 1.45^**

69.68 ± 1.37^**

79.84 ± 1.45^**##

10d

58.57 ± 1.01

59.50 ± 0.98^##^△△

64.64 ± 1.22^**##

66.96 ± 1.41^**##^△△

10e

58.19 ± 1.06

59.61 ± 1.22^##^△

64.64 ± 0.81^**##

66.90 ± 0.64^**##^△△

10f

59.77 ± 2.63

60.83 ± 2.70^##

65.54 ± 2.30^**##

68.49 ± 2.40^**##^△△

10g

58.60 ± 2.89

65.42 ± 0.95^**

72.07 ± 2.70^**^△△

86.36 ± 2.14^**^△△

10h

59.62 ± 0.55

68.59 ± 1.16^**##^△△

79.64 ± 1.84^**##^△△

85.64 ± 0.90^**^△△

10i

58.59 ± 1.03

72.83 ± 1.64^**##^△△

81.75 ± 1.07^**##^△△

88.34 ± 1.34^**^△△

10j

58.77 ± 2.31

67.61 ± 1.43^**^△△

75.36 ± 2.58^**#^△△

81.99 ± 2.69^**##

10k

59.11 ± 1.30

60.14 ± 1.17^##

61.73 ± 2.25^*##^△△

63.41 ± 1.77^**##^△△

10l

59.77 ± 2.03

61.45 ± 2.24^#

62.44 ± 2.22^*##^△△

63.26 ± 2.84^**##^△△

10m

58.75 ± 0.76

59.32 ± 1.48^##^△△

62.37 ± 2.36^**##^△△

64.91 ± 1.71^**##^△△

10n

60.72 ± 1.63

62.13 ± 2.01

63.33 ± 1.89^*##^△△

64.62 ± 1.83^**##^△△

10o

58.30 ± 1.81

59.84 ± 0.68^##^△

62.74 ± 1.95^**##^△△

64.94 ± 1.68^**##^△△

10p

57.90 ± 1.00

67.60 ± 1.65^**^△△

73.79 ± 1.14^**^△△

79.51 ± 1.46^**##

11a

59.56 ± 1.47

66.76 ± 0.51^**^△

72.01 ± 1.33^**^△△

79.99 ± 1.88^**##

11b

59.00 ± 0.69

61.91 ± 0.96^*

68.82 ± 1.37^**#

77.72 ± 1.76^**##

11c

58.36 ± 1.30

61.50 ± 1.96^*

69.72 ± 2.10^**

78.29 ± 1.32^**##

11d

58.68 ± 1.10

62.30 ± 0.94^**

69.40 ± 1.71^**

77.64 ± 0.32^**##