Please cite this article in press as: Brand et al., Combined Proteomic and In Silico Target Identification Reveal a Role for 5-Lipoxygenase in Develop-
The crude product was purified by HPLC (method 3). The resulting trifluoroacetate salt was partitioned between ethyl acetate and
aqueous 2M Na2CO3 solution (2:1 ratio v/v). The heterogeneous mixture was rapidly stirred at ambient temperature for 30 min. The
organic layer was separated, washed with brine and dried over MgSO4. The solvent was removed under reduced pressure to give the
title product.
Colorless oil, 59%; Rf: 0.24 (2% methanol/dichloromethane); 1H-NMR (600 MHz, CDCl3): d = 3.23 (s, 3H), 3.94 (s, 3H), 3.97 (s, 3H),
6.42 (s, 1H), 6.94-6.98 (m, 1H), 7.40 (dd, 3J = 8.2, 4.2 Hz, 1H), 7.59-7.61 (m, 1H), 7.74 (d, 3J = 8.8 Hz, 1H), 7.85 (s, 1H), 8.04 (s, 1H), 8.08
(d, 3J = 8.8 Hz, 1H), 8.16 (d, 3J = 8.2 Hz, 1H), 8.20 (d, 3J = 4.2 Hz, 1H), 8.87 (d, 4J = 3.8 Hz, 1H); 13C-NMR (151 MHz, CDCl3): d = 53.81,
54.15, 60.88, 68.10, 116.96, 117.06, 118.52, 119.85, 121.34, 123.70, 128.14, 128.29, 129.06, 136.67, 139.72, 142.71, 146.96, 147.27,
149.11, 149.94, 161.43, 162.18, 164.15; ESI-MS: m/z 404.23 [M+H]+; HRMS (ESI): calculated for C23H22O4N3 m/z 404.16048 [M+H]+,
found m/z 404.15876 [M+H]+.
( )-Cyclohexyl(2’,4,6-trimethoxy-[3,3’-bipyridin]-5-yl)methanol (1q)
Colorless oil, 28%; Rf: 0.38 (50% ethyl acetate/petroleum ether); 1H-NMR (400 MHz, CDCl3): d = 0.94-1.35 (m, 6H), 1.60-1.70
(m, 2H), 1.72-1.84 (m, 2H), 2.21 (d, 3J = 12.9 Hz, 1H), 3.28 (bs, 1H), 3.38 (s, 3H), 3.92 (s, 3H), 4.01 (s, 3H), 4.70 (d, 3J = 8.3 Hz,
3
1H), 6.96 (dd, J = 7.2, 5.0 Hz, 1H), 7.57 (dd, 3,4J = 7.3, 1.9 Hz, 1H), 7.95 (s, 1H), 8.20 (dd, 3,4J = 5.0, 1.9 Hz, 1H); 13C-NMR (101
MHz, CDCl3): d = 26.17, 26.34, 26.63, 29.70, 30.08, 43.96, 53.77, 53.91, 60.88, 72.33, 116.92, 117.16, 119.03, 119.68, 139.75,
146.74, 147.87, 161.54, 162.37, 164.20; ESI-MS: m/z 359.21 [M+H]+; HRMS (ESI): calculated for C20H27O4N2 m/z 359.19653
[M+H]+, found m/z 359.19672 [M+H]+.
( )-1-(2’,4,6-Trimethoxy-[3,3’-bipyridin]-5-yl)decan-1-ol (1r)
Colorless oil, 71%; Rf: 0.25 (30% ethyl acetate/petroleum ether); 1H-NMR (500 MHz, CDCl3): d = 0.87 (t, 3J = 6.9 Hz, 3H), 1.20-1.37
(m, 13H), 1.46-1.57 (m, 1H), 1.68-1.76 (m, 1H), 1.87-1.96 (m, 1H), 3.36 (d, 3J = 10.3 Hz, 1H), 3.41 (s, 3H), 3.93 (s, 3H), 4.02 (s, 3H), 4.98-
5.06 (m, 1H), 6.96 (dd, 3J = 7.2, 5.0 Hz, 1H), 7.57 (dd, 3,4J = 7.3, 1.9 Hz, 1H), 7.96 (s, 1H), 8.20 (dd, 3,4J = 5.0, 1.9 Hz, 1H); 13C-NMR (126
MHz, CDCl3): d = 14.25, 22.82, 26.37, 29.48, 29.66, 29.74, 29.79, 32.05, 37.69, 53.78, 53.91, 61.04, 67.70, 116.92, 118.34, 118.87,
119.89, 139.83, 146.75, 147.81, 161.53, 162.34, 163.62; ESI-MS: m/z 403.27 [M+H]+; HRMS (ESI): calculated for C23H35O4N2 m/z
403.25913 [M+H]+, found m/z 403.25559 [M+H]+.
( )-(5-(3,4-Bis((tert-butyldimethylsilyl)oxy)phenyl)-2,4-dimethoxypyridin-3-yl)-(naphthalen-2-yl)methanol (11)
Colorless oil, 98%; Rf: 0.29 (20% ethyl acetate/petroleum ether); 1H-NMR (400 MHz, CDCl3): d = 0.23 (s, 6H), 0.24 (s, 6H), 1.00 (s,
9H), 1.01 (s, 9H), 3.19 (s, 3H), 3.99 (s, 3H), 4.25 (d, 3J = 11.7 Hz, 1H), 6.43 (d, 3J = 11.4 Hz, 1H), 6.89 (d, 3J = 8.2 Hz, 1H), 6.95 (dd, 3,4J =
6.8, 2.2 Hz, 1H), 7.00 (d, 4J = 2.1 Hz, 1H), 7.41-7.49 (m, 2H), 7.52 (dd, 3,4J = 8.6, 1.6 Hz, 1H), 7.77-7.85 (m, 4H), 8.06 (s, 1H); 13C-NMR
(101 MHz, CDCl3): d = -3.92, -3.90. 18.62, 26.07, 54.09, 60.58, 68.57, 118.03, 121.39, 121.72, 122.03, 123.85, 124.48, 125.09, 125.80,
126.14, 127.71, 128.00, 128.15, 128.44, 132.73, 133.36, 141.70, 146.82, 147.17, 147.77, 161.68, 163.82; ESI-MS: m/z 632.66
[M+H]+; HRMS (ESI): calculated for C36H50O5NSi2 m/z 632.32220 [M+H]+, found m/z 632.32227 [M+H]+.
( )-(5-(4-((tert-Butyldimethylsilyl)oxy)phenyl)-2,4-dimethoxypyridin-3-yl)(naphthalen-2-yl)methanol (12)
Cell Chemical Biology 25, 1–12.e1–e23, September 20, 2018 e13