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1H), 7.87 (s, 1H), 7.74 (d, J ¼ 8.4 Hz, 2H), 7.43 (s, 1H), 7.34 (d, J ¼ 145.7, 139.9, 139.7, 136.0, 135.8, 133.9, 129.0, 128.4, 127.6,
8.4 Hz, 1H), 7.28 (d, J ¼ 8.4 Hz, 1H), 6.66 (d, J ¼ 5.2 Hz, 1H), 126.8, 126.6, 125.7, 124.4, 123.8, 122.4, 118.6, 114.1, 112.3,
5.44–5.35 (m, 2H), 5.34 (s, 1H), 5.23 (d, J ¼ 6.4 Hz, 1H), 4.05 (s, 110.0, 90.5, 76.0, 69.8, 61.8, 57.0, 55.8, 55.4. HRMS (EI) calcd for
3H), 3.98 (s, 3H), 3.91 (s, 3H), 2.89 (s, 3H). 13C NMR (125 MHz,
C
34H31O6N 549.2146 [M]+, found 549.2146.
DMSO-d6) d 160.6, 152.5, 150.8, 147.3, 147.1, 145.7, 144.6, 135.8,
5-(3-((4-(tert-Butyl)benzyl)oxy)-4-methoxyphenyl)-3,9,10-trime-
133.9, 128.3, 125.7, 124.4, 123.8, 123.6, 122.9, 118.6, 114.4, thoxy-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
(23m).
112.4, 110.1, 90.5, 75.9, 69.1, 61.8, 56.9, 55.9, 55.3. HRMS (EI) Compound 23m was prepared from compound 22m (56 mg, 0.1
calcd for C28H26O8N2 518.1684 [M]+, found 518.1688.
3,9,10-Trimethoxy-5-(4-methoxy-3-((4-(triuoromethyl)benzyl)
oxy)phenyl)-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
mmol) as a yellow solid (46 mg, 86%). 1H NMR (500 MHz,
DMSO-d6) d 8.18 (d, J ¼ 7.2 Hz, 1H), 8.02 (d, J ¼ 6.8 Hz, 1H), 7.88
(23i). (s, 1H), 7.44 (d, J ¼ 5.6 Hz, 3H), 7.40 (d, J ¼ 6.4 Hz, 2H), 7.30 (d, J
Compound 23i was prepared from compound 22i (57 mg, 0.1 ¼ 6.8 Hz, 1H), 7.23 (d, J ¼ 6.8 Hz, 1H), 6.56 (s, 1H), 5.32 (m, 1H),
mmol) as a yellow solid (48 mg, 88%). 1H NMR (500 MHz, 5.26 (m, 1H), 5.17 (m, 2H), 4.05 (s, 3H), 3.99 (s, 3H), 3.88 (s, 3H),
DMSO-d6) d 8.20 (d, J ¼ 7.2 Hz, 1H), 8.03 (d, J ¼ 6.8 Hz, 1H), 7.89 2.82 (s, 3H), 1.29 (s, 9H). 13C NMR (125 MHz, DMSO-d6) d 161.1,
(s, 1H), 7.82 (d, J ¼ 6.0 Hz, 2H), 7.72 (d, J ¼ 6.4 Hz, 2H), 7.46 (s, 153.0, 151.3, 151.1, 148.2, 146.2, 136.5, 134.5, 134.1, 128.3,
1H), 7.35 (d, J ¼ 6.4 Hz, 1H), 7.28 (d, J ¼ 6.4 Hz, 1H), 6.64 (s, 1H), 126.2, 125.7, 124.9, 124.3, 122.8, 119.0, 114.4, 112.7, 110.5, 91.0,
5.36 (m, 3H), 5.27 (s, 1H), 4.07 (s, 3H), 4.01 (s, 3H), 3.93 (s, 3H), 76.5, 70.3, 62.3, 57.5, 56.3, 55.9, 34.8, 31.6. HRMS (EI) calcd for
2.88 (s, 3H). 13C NMR (125 MHz, DMSO-d6) d 160.6, 152.5, 150.8,
C
32H35O6N 529.2459 [M]+, found 529.2459.
147.4, 145.7, 141.6, 135.9, 133.9, 128.1, 125.7, 125.4, 125.4,
5-(3-((4-Isopropylbenzyl)oxy)-4-methoxyphenyl)-3,9,10-trime-
124.4, 123.8, 122.7, 119.4, 118.6, 114.3, 112.4, 110.1, 90.5, 75.9, thoxy-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
(23n).
69.3, 61.8, 56.9, 55.9, 55.3. HRMS (EI) calcd for C29H26O6NF3 Compound 23n was prepared from compound 22n (55 mg, 0.1
541.1707 [M]+, found 541.1710.
3,9,10-Trimethoxy-5-(4-methoxy-3-(quinolin-7-ylmethoxy)
phenyl)-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
mmol) as a yellow solid (50 mg, 90%).1H NMR (600 MHz,
DMSO-d6) d 8.18 (d, J ¼ 6.0 Hz, 1H), 8.01 (d, J ¼ 6.0 Hz, 1H), 7.87
(23j). (s, 1H), 7.43 (d, J ¼ 1.2 Hz, 1H), 7.39 (d, J ¼ 5.2 Hz, 2H), 7.31–
Compound 23j was prepared from compound 22j (58 mg, 0.1 7.27 (m, 3H), 7.22 (d, J ¼ 5.6 Hz, 1H), 6.55 (d, J ¼ 4.0 Hz, 1H),
mmol) as a yellow solid (45 mg, 85%). 1H NMR (400 MHz, 5.31 (m, 1H), 5.24 (m, 1H), 5.18 (m, 1H), 5.13 (m, 1H), 4.05 (s,
DMSO-d6) d 8.99 (s, 1H), 8.57 (d, J ¼ 7.2 Hz, 1H), 8.18 (d, J ¼ 3H), 3.98 (s, 3H), 3.87 (s, 3H), 2.94–2.85 (m, 1H), 2.82 (s, 3H),
8.0 Hz, 1H), 8.07 (d, J ¼ 7.6 Hz, 1H), 8.00 (s, 2H), 7.89 (s, 1H), 1.20 (s, 3H), 1.19 (s, 3H). 13C NMR (125 MHz, DMSO-d6) d 161.1,
7.73 (s, 1H), 7.70 (s, 1H), 7.57 (s, 1H), 7.32 (d, J ¼ 5.6 Hz, 1H), 153.0, 151.3, 148.8, 148.2, 146.2, 136.5, 134.5, 134.4, 128.5,
7.26 (d, J ¼ 7.2 Hz, 1H), 6.74 (s, 1H), 5.91 (m, 1H), 5.82 (m, 1H), 126.9, 126.1, 124.9, 124.3, 122.8, 119.0, 114.4, 112.7, 110.5, 91.0,
5.34 (m, 1H), 5.23 (s, 1H), 4.04 (s, 3H), 3.96 (s, 3H), 3.89 (s, 3H), 76.4, 70.4, 62.3, 57.4, 56.3, 55.9, 33.7, 24.3. HRMS (EI) calcd for
2.93 (s, 3H). 13C NMR (125 MHz, DMSO-d6) d 161.1, 153.0, 151.2,
C
31H33O6N 515.2302 [M]+, found 515.2295.
150.0, 148.5, 146.2, 136.5, 134.5, 134.0, 129.8, 129.2, 128.7,
5-(3-((3,5-Dimethoxybenzyl)oxy)-4-methoxyphenyl)-3,9,10-tri-
128.4, 127.3, 126.1, 125.0, 124.4, 122.9, 122.3, 119.1, 115.7, methoxy-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
(23o).
114.3, 112.8, 110.6, 91.0, 76.5, 67.0, 62.3, 57.5, 56.4, 55.8. HRMS Compound 23o was prepared from compound 22o (56 mg, 0.1
(EI) calcd for C31H28O6N2 524.1942 [M]+, found 524.1951.
3,9,10-Trimethoxy-5-(4-methoxy-3-((4-methylbenzyl)oxy)
phenyl)-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
mmol) as a yellow solid (51 mg, 95%). 1H NMR (500 MHz,
DMSO-d6) d 8.18 (d, J ¼ 8.5 Hz, 1H), 8.00 (d, J ¼ 9.0 Hz, 1H), 7.87
(23k). (m, 1H), 7.39 (s, 1H), 7.32–7.26 (m, 1H), 7.24 (d, J ¼ 8.5 Hz, 1H),
Compound 23k was prepared from compound 22k (52 mg, 0.1 6.62 (s, 2H), 6.52 (s, 1H), 6.47 (s, 1H), 5.33 (m, 1H), 5.26–5.17 (m,
mmol) as a yellow solid (45 mg, 92%). 1H NMR (400 MHz, 1H), 5.15 (s, 2H), 4.05 (s, 3H), 3.98 (s, 3H), 3.90 (s, 3H), 3.74 (s,
DMSO-d6) d 8.16 (s, 1H), 7.99 (s, 1H), 7.85 (s, 1H), 7.39 (s, 1H), 6H), 2.84 (s, 3H). 13C NMR (125 MHz, DMSO-d6) d 161.1, 161.1,
7.33 (s, 2H), 7.26 (s, 1H), 7.20 (s, 3H), 6.54 (s, 1H), 5.31 (s, 1H), 153.0, 151.4, 148.0, 146.2, 139.5, 136.5, 134.4, 126.2, 124.9,
5.13 (s, 3H), 4.02 (s, 3H), 3.95 (s, 3H), 3.85 (s, 3H), 2.82 (s, 3H), 124.2, 123.0, 119.0, 114.7, 112.9, 110.5, 106.1, 99.8, 91.0, 76.4,
2.28 (s, 3H). 13C NMR (125 MHz, DMSO-d6) d 160.6, 152.4, 150.8, 70.4, 62.3, 57.5, 56.4, 55.9, 55.7. HRMS (EI) calcd for C30H31O8N
147.6, 145.7, 137.3, 136.0, 133.9, 133.5, 129.0, 127.9, 125.7, 533.2044 [M]+, found 533.2031.
124.5, 123.7, 122.4, 118.5, 114.1, 112.3, 110.0, 90.5, 76.0, 70.0,
61.9, 57.1, 55.9, 55.4, 20.8. HRMS (EI) calcd for C29H29O6N
Biology
487.1989 [M]+, found 487.1989.
5-(3-([1,10-Biphenyl]-4-ylmethoxy)-4-methoxyphenyl)-3,9,10-tri-
Materials. Fluorescein diacetate (FD) and loperamide (LPA)
(23l). were purchased from TCI (Tokyo Japan), Luciferin Detection
Compound 23l was prepared from compound 22l (58 mg, 0.1 Reagent (LDR) was purchased from Promega Corporation
mmol) as a yellow solid (45 mg, 81%). 1H NMR (500 MHz, (USA).
N-(2-Butyl-1,3-dioxo-2,3-dihydro-1H-phenalen-6-yl)-2-
methoxy-2,3-dihydrooxazolo[2,3-a]isoquinolin-4-ium
DMSO-d6) d 8.20 (d, J ¼ 6.8 Hz, 1H), 8.03 (d, J ¼ 6.8 Hz, 1H), 7.90 chloroacetamide (NCEN) and D-luciferin methyl ester (DME)
(s, 1H), 7.74 (d, J ¼ 6.0 Hz, 2H), 7.70 (d, J ¼ 6.0 Hz, 2H), 7.58 (d, J were synthesized by authors according to the previously re-
¼ 6.0 Hz, 2H), 7.53–7.47 (m, 3H), 7.40 (t, J ¼ 6.0 Hz, 1H), 7.33 (d, ported synthetic scheme.37,38 Nevadensin was purchased from
J ¼ 6.4 Hz, 1H), 7.27 (d, J ¼ 6.4 Hz, 1H), 6.63 (s, 1H), 5.34 (m, Chengdu Preferred Biotech Co., Ltd. (Chengdu, China). Pooled
1H), 5.27 (m, 3H), 4.07 (s, 3H), 4.00 (s, 3H), 3.93 (s, 3H), 2.88 (s, human liver microsomes (HLMs, from 50 donors, lot no.
3H). 13C NMR (125 MHz, DMSO-d6) d 160.6, 152.5, 150.8, 147.7, X008067) were obtained from Bioreclamation IVT (Baltimore,
35910 | RSC Adv., 2019, 9, 35904–35912
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