Molecules 2018, 23, 2084
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J = 5.0 Hz, 2H), 3.95 (s, 6H), 3.88 (s, 3H), 3.83 (s, 3H), 3.24 (t, J = 5.0 Hz, 2H). 13C-NMR (101 MHz)
δ 194.2,
159.4, 151.4, 148.8, 148.6, 145.7, 141.9, 137.6, 135.3, 133.0, 130.1, 128.5, 126.7, 122.8, 121.0, 120.1, 119.8,
119.7, 118.8, 112.2, 111.2, 108.7, 74.8, 57.0, 56.1, 55.8, 55.5, 55.3, 26.0. HRMS: calcd. for C29H28ClNO6
[M]+: 486.1911, found: 486.1916.
2,3,10-Trimethoxy-9-p-trifloromethylphenylformylmethylenoxy protoberberine chloride (4f). Compound
3
(373 mg, 1 mmol) was treated with 4-(trifluoromethyl) phenacyl bromide (534 mg, 2 mmol) according
to the general procedure to give the desired product 4f. Yield: 29%; red brown solid; m.p. 240–242 ◦C;
1H-NMR (400 MHz)
δ
10.01 (s, 1H), 9.05 (s, 1H), 8.21–8.18 (m, 3H), 8.03–7.96 (m, 3H), 7.74 (s, 1H), 7.12
(s, 1H), 5.93 (s, 2H), 4.97 (t, J = 5.0 Hz, 2H), 3.95 (d, J = 5.0 Hz, 6H), 3.88 (s, 3H), 3.25 (t, J = 5.0 Hz, 2H).
13C-NMR (101 MHz)
194.0, 151.4, 148.8, 148.6, 145.7, 141.7, 137.7, 137.3, 133.0, 128.6 (2), 128.5, 126.7,
δ
125.8 (2), 125.3, 124.9, 122.94, 120.9, 119.77, 118.7, 111.2, 108.7, 75.0, 57.0, 56.1, 55.8, 55.5, 25.9. HRMS:
calcd. for C29H25ClF3NO5 [M]+: 524.1679, found: 524.1686.
2,3,10-Trimethoxy-9-benzyloxyformyloxy protoberberine chloride (4g). Compound
3 (373 mg, 1 mmol) was
treated with benzyl chloroformate (682.4 mg, 4 mmol) according to the general procedure to give the
◦
desired product 4g. Yield: 21%; yellow solid; m.p. 98–100 C; 1H-NMR (400 MHz)
δ 10.02 (s, 1H), 9.16
(s, 1H), 8.29 (dd, J = 10.0 Hz, J = 25.0 Hz, 2H), 7.74 (s, 1H), 7.53–7.43 (m, 5H), 7.11 (s, 1H), 5.41 (s, 2H),
4.96 (t, J = 5.0 Hz, 2H), 4.03 (s, 3H), 3.95 (s, 3H), 3.88 (s, 3H), 3.24 (t, J = 5.0 Hz, 2H). 13C-NMR (101 MHz)
δ
151.6, 150.0, 148.6, 144.2, 138.4, 134.6, 133.3, 132.8, 128.7, 128.6, 128.5 (2), 128.1 (2), 126.9, 125.9, 120.4,
120.2, 118.7, 111.2, 108.7, 70.7, 57.2, 56.1, 55.8, 55.4, 45.3, 25.7. HRMS: calcd. for C28H26ClNO6 [M]+:
472.1755, found: 472.1758.
3.2.3. General Procedure for the Synthesis of Compounds 5a–g
To a stirred solution of JTH (100 m◦g, 0.29 mmol) in anhydrous CH3CN or DMF, K2CO3 (122 mg,
0.88 mmol) was added and heated to 70 C. Then R1Br or benzyl chloroformate (2–4 eq) was added and
stirred for 5–6 h. The mixture was cooled to precipitate completely, filtrated and washed by CH2Cl2 to
afford compounds 5a–g.
2,9,10-Trimethoxy-3-ethyloxyformylmethylenoxy protoberberine chloride (5a). JTH (373 mg, 1 mmol) was
treated with ethyl bromoacetate (668 mg, 4 mmol) according to the general procedure to give the
desired product 5a. Yield: 35%; yellow solid; m.p. 234–236 ◦C; 1H-NMR (500 MHz)
δ 9.91 (s, 1H), 9.07
(s, 1H), 8.23 (d, J = 10.0 Hz, 1H), 8.06–8.04 (m, 1H), 7.76 (s, 1H), 7.04 (s, 1H), 4.94 (t, J = 5.0 Hz, 2H), 4.92
(s, 2H), 4.20 (dd, J = 5.0 Hz, J = 15.0 Hz, 2H), 4.10 (s, 3H), 4.08 (s, 3H), 3.97 (s, 3H), 3.19 (t, J = 5.0 Hz,
2H), 1.24 (t, J = 5.0 Hz, 3H). 13C-NMR (126 MHz)
δ 168.2, 150.2, 149.5, 148.6, 145.4, 143.5, 137.4, 132.9,
128.2, 126.6, 123.3, 121.3, 112.0, 119.7, 112.4, 109.1, 64.9, 61.8, 60.7, 56.9, 56.1, 55.2, 25.7, 14.0. HRMS:
calcd. for C24H26ClNO6 [M]+: 424.1755, found: 424.1751.
2,9,10-Trimethoxy-3-pivalylmethylenoxy protoberberine chloride (5b). JTH (373 mg, 1 mmol) was treated
with 1-bromo-3,3-dimethyl-2-butanone (358.1 mg, 2 mmol) according to the general procedure to give
the desired product 5b. Yield: 28%; yellow solid; m.p. 223–225 ◦C; 1H-NMR (500 MHz)
δ 9.90 (s, 1H),
9.05 (s, 1H), 8.23 (d, J = 5.0 Hz, 1H), 8.05 (d, J = 5.0 Hz, 1H), 7.74 (s, 1H), 6.88 (s, 1H), 5.27 (s, 2H), 4.94 (t,
J = 5.0 Hz, 2H), 4.10 (s, 3H), 4.08 (s, 3H), 3.96 (s, 3H), 3.18 (t, J = 5.0 Hz, 2H), 1.20 (s, 9H). 13C NMR
(126 MHz)
δ
209.2, 150.2, 145.0, 148.6, 145.3, 143.5, 137.5, 132.9, 128.1, 126.6, 123.3, 121.2, 119.8, 119.1,
209.2, 150.2, 145.0,
112.0, 109.1, 68.8, 61.8, 56.9, 56.1, 55.2, 42.4, 25.8, 25.6 (3). 13C-NMR (126 MHz)
δ
148.6, 145.3, 143.5, 137.5, 132.9, 128.1, 126.6, 123.3, 121.2, 119.8, 119.1, 112.0, 109.1, 68.8, 61.8, 56.9, 56.1,
55.2, 42.4, 25.8, 25.6 (3). HRMS: calcd. for C26H30 ClNO5 [M]+: 436.2119, found: 436.2118.
2,9,10-Trimethoxy-3-benzyloxyformylmethylenoxy protoberberine chloride (5c). JTH (373 mg, 1 mmol) was
treated with benzyl bromoacetate (916.2 mg, 4 mmol) according to the general procedure to give the
desired product 5c. Yield: 38%; yellow solid; m.p. 217–219 ◦C; 1H-NMR (500 MHz)
δ 9.90 (s, 1H), 9.06
(s, 1H), 8.23 (d, J = 10.0 Hz, 1H), 8.04 (d, J = 10.0 Hz, 1H), 7.75 (s, 1H), 7.40–7.35 (m, 4H), 7.03 (s, 1H),
5.23 (s, 2H), 5.01 (s, 2H), 4.93 (t, J = 5.0 Hz, 2H), 4.10 (s, 3H), 4.08 (s, 3H), 3.96 (s, 3H), 3.16 (t, J = 5.0 Hz,