6916
M. E. Bolitho et al. / Bioorg. Med. Chem. 19 (2011) 6906–6918
achieved using flash silica gel chromatography, gradient of hexanes
to 20% EtOAc/Hex to give C9. 1H NMR (500 MHz, CDCl3) d 7.10 (d, J
= 8.8 Hz, 1H), 7.02–7.00 (m, 2H), 4.99 (d, J = 4.4 Hz, 1H), 4.31 (d,
J = 4.5 Hz, 1H), 2.40–2.26 (m, 2H), 2.23 (s, 6H), 1.53–1.40 (m, 2H),
1.31–1.02 (m, 12H), 0.84 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz,
CDCl3) d 210.3, 137.5, 137.3, 135.7, 130.3, 128.6, 125.2, 79.6,
37.9, 32.0, 29.1, 29.1, 29.0, 23.9, 22.8, 19.9, 19.7, 14.3. HRMS
(ESI-TOF) calcd for C19H30O2Na, 313.2143; observed, 313.2141
[M+Na]+.
J = 3.9 Hz, 1H), 4.35 (d, J = 4.1 Hz, 1H), 2.36–2.21 (m, 2H), 1.57–
1.40 (m, 2H), 1.30–1.03 (m, 12H), 0.84 (t, J = 6.9 Hz, 3H); 13C
NMR (125 MHz, CDCl3) d 210.2, 156.2, 130.4, 129.2, 116.1, 79.2,
38.0, 32.0, 29.4, 29.3, 29.2, 23.9, 22.9, 14.3. HRMS (ESI-TOF) calcd
for C17H26O3Na, 301.1780; observed 301.1773 [M+Na]+.
4.6.3.3.12.
1-Hydroxy-1-(3,4-dihydroxyphenyl)undecan-2-one
(C15).. Prepared according to the standard procedure utilizing
the 2-nonyl-1,3-dithiane and bis-TBS protected 3,4-dihydroxy-
benzaldehyde. Final deprotection was achieved under standard
TBAF conditions (6.0 equiv TBAF, 1 M in THF, rt). Purification was
achieved using flash silica gel chromatography, gradient of 20%
EtOAc/Hex to 60% EtOAc/Hex to provide C15. 1H NMR (500 MHz,
CDCl3) 6.88–6.75 (m, 1H), 6.75–6.63 (m, 2H), 5.83 (br s, 2H), 4.94
(s, 1H), 4.44 (br s, 1H), 2.37–2.23 (m, 2H), 1.78–1.56 (m, 2H),
1.56–1.40 (m, 2H), 1.33–1.06 (m, 10H), 0.84 (t, J = 6.7 Hz, 3H). 13C
NMR (125 MHz, CDCl3) d 210.2, 144.6, 144.2, 130.5, 120.8, 115.9,
114.4, 79.3, 37.9, 32.5, 29.6, 29.4, 29.4, 29.2, 23.9, 22.9, 14.3. HRMS
(ESI-TOF) calcd for C17H26O4Na, 317.1723; observed 317.1724
[M+Na]+.
4.6.3.3.13. 1-Hydroxy-1-(2-methoxyphenyl)undecan-2-one (C16).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 2-methoxybenzaldehyde. Purification was
achieved using flash silica gel chromatography, gradient of hexanes
to 10% EtOAc/Hex to give C16 (0.026 g, 0.089 mmol, 26%). 1H NMR
(500 MHz, CDCl3) d 7.35 (m, 1H), 7.24 (m, 1H), 6.97 (m, 1H), 6.91
(m, 1H), 5.38 (d, J = 4.7 Hz, 1H), 4.29 (d, J = 4.8 Hz, 1H), 3.85 (s,
3H), 2.33 (m, 2H), 1.51 (m, 2H), 1.15 (m, 12H), 0.87 (t, J = 6.8 Hz,
3H). 13C NMR (125 MHz, CDCl3) d 209.0, 155.9, 128.8, 128.2,
125.5, 120.0, 110.0, 73.8, 54.4, 36.4, 30.8, 28.3, 28.2, 28.2, 28.0,
22.7, 21.6, 13.1. HRMS (EI) calcd for C18H28O3, 292.2038; observed,
292.2038 [M]+.
4.6.3.3.7.
1-(4-Ethylphenyl)-1-hydroxyundecan-2-one (C10).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 4-ethylbenzaldehyde. Purification was achieved
using flash silica gel chromatography, gradient of hexanes to 20%
EtOAc/Hex to give C10 1H NMR (500 MHz, CDCl3) d 7.20–7.17 (m,
4H), 5.03 (s, 1H), 4.33 (s, 1H), 2.63 (q, J = 7.6 Hz, 2H), 2.39–2.19
(m, 2H), 1.55–1.36 (m, 2H), 1.32–1.06 (m, 15H), 0.84 (t,
J = 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 210.2, 145.0, 135.5,
128.6, 127.6, 79.6, 37.9, 32.0, 28.8, 28.7, 28.7, 28.6, 23.9, 22.9,
15.7, 14.3. HRMS (ESI-TOF) calcd for C19H30O2Na, 313.2143; ob-
served, 313.2142 [M+Na]+.
4.6.3.3.8. 1-Hydroxy-1-(4-propylphenyl)-undecan-2-one (C11).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 4-propylbenzaldehyde. Purification was achieved
using flash silica gel chromatography, gradient of hexanes to 10%
EtOAc/Hex to give C11. 1H NMR (400 MHz, CDCl3) d 7.20 (d,
J = 8 Hz, 2H), 7.18 (d, J = 8 Hz, 2H), 5.05 (s, 1H), 2.58 (t, J = 7 Hz,
2H), 2.33 (m, 2H), 1.64 (m, 2H), 1.48 (m, 2H), 1.10–1.30 (m,
12H), 0.93 (t, J = 7 Hz, 3H), 0.87 (t, J = 7 Hz, 3H). 13C NMR
(100 MHz, CDCl3) d 210.2, 143.5, 135.6, 129.3, 127.6, 79.7, 38.1,
37.9, 32.1, 29.5, 29.4, 29.2, 24.7, 24.0, 22.9, 14.3, 14.0. HRMS (EI)
calcd for C20H32O2, 304.24023; observed 304.2402 [M]+.
4.6.3.3.9. 1-Hydroxy-1-(2-hydroxyphenyl)undecan-2-one (C12).
Prepared according to the standard procedure utilizing the 2-non-
yl-1,3-dithiane and TBS protected 2-hydroxybenzaldehyde. Final
deprotection was achieved under standard TBAF conditions
(3.0 equiv TBAF, 1 M in THF, rt). Purification was achieved using
flash silica gel chromatography, gradient of 20% EtOAc/Hex to
40% EtOAc/Hex to provide C12 (0.025 g, 0.090 mmol, 33%). 1H
NMR (400 MHz, CDCl3) d 7.25 (m, 2H), 6.96 (m, 1H), 6.88 (m,
1H), 5.18 (s, 1H), 2.83 (s, 1H), 2.37 (m, 2H), 1.51 (m, 2H), 1.11
(m, 12H), 0.88 (t, J = 7.0 Hz, 3H). 13C NMR (126 MHz, CDCl3) d
204.9, 149.9, 125.0, 124.3, 116.7, 115.5, 112.2, 73.8, 32.2, 26.6,
24.0, 23.9, 23.6, 18.3, 17.4, 8.9. HRMS (EI) calcd for C17H26O3,
278.1882; observed 278.1881 [M]+.
4.6.3.3.10. 1-Hydroxy-1-(3-hydroxyphenyl)undecan-2-one (C13).
Prepared according to the standard procedure utilizing the 2-non-
yl-1,3-dithiane and TBS protected 3-hydroxybenzaldehyde. Final
deprotection was achieved under standard TBAF conditions
(3.0 equiv TBAF, 1 M in THF, rt). Purification was achieved using
flash silica gel chromatography, gradient of 20% EtOAc/Hex to
40% EtOAc/Hex to provide C13 (0.02 g, 0.072 mmol, 27%). 1H
4.6.3.3.14. 1-Hydroxy-1-(3-methoxyphenyl)undecan-2-one (C17).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 3-methoxybenzaldehyde. Purification was
achieved using flash silica gel chromatography, gradient of hexanes
to 10% EtOAc/Hex to give C17 (0.007 g, 0.024 mmol, 9%). 1H NMR
(500 MHz, CDCl3) d 7.23 (m, 1H), 6.80 (m, 3H), 4.98 (d, J = 4.4 Hz,
1H), 4.31 (d, J = 4.4 Hz, 1H), 3.74 (s, 3H), 2.27 (m, 2H), 1.42 (m,
2H), 1.11 (m, 12H), 0.80 (t, J = 6.9 Hz, 3H). 13C NMR (125 MHz,
CDCl3) d 208.5, 158.5, 139.6, 130.0, 119.9, 114.3, 112.6, 79.1,
55.3, 37.8, 31.9, 29.4, 29.2, 29.0, 23.7, 22.7, 14.2. HRMS (EI) calcd
for C18H28O3, 292.2038; observed, 292.2038 [M]+.
4.6.3.3.15. 1-Hydroxy-1-(4-methoxyphenyl)-undecan-2-one (C18).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 4-methoxybenzaldehyde. Purification was
achieved using flash silica gel chromatography, gradient of hexanes
to 10% EtOAc/Hex to give C18 (0.08 g, 2.7 mmol, 80%). 1H NMR
(500 MHz, CDCl3) d 7.22 (m, 2H), 6.86 (m, 2H), 5.05 (d, J = 9.5 Hz,
1H), 4.35 (d, J = 9.5 Hz, 1H), 3.81 (s, 3H), 2.31 (m, 2H), 1.50 (m,
2H), 1.20 (m, 12H), 0.87 (t, J = 7.1 Hz, 3H). 13C NMR (125 MHz,
CDCl3) d 210.2, 160.0, 130.3, 129.2, 114.7, 79.3, 55.5, 38.0, 32.0,
29.5, 29.4, 29.4, 29.1, 24.2, 22.8, 14.3. HRMS (EI) calcd for
NMR (500 MHz, CDCl3)
d 7.22 (t, J = 7.9 Hz, 1H), 6.86 (d,
J = 7.6 Hz, 1H), 6.78 (dd, J = 8.1, 2.5 Hz, 1H), 6.73 (s, 1H), 5.93 (br
s, 1H), 5.03 (s, 1H), 4.61 (br s, 1H), 2.36 (m, 2H), 1.50 (m, 2H),
1.22 (m, 12H), 0.87 (t, J = 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3)
d 209.9, 156.6, 139.4, 130.5, 112.0, 116.2, 114.3, 79.5, 38.0, 32.0,
29.5, 29.4, 29.1, 23.8, 22.9, 14.3. HRMS (EI) calcd for C17H26O3,
278.1882; observed, 278.1879 [M]+.
4.6.3.3.11. 1-Hydroxy-1-(4-hydroxyphenyl)undecan-2-one (C14).
Prepared according to the standard procedure utilizing the 2-non-
yl-1,3-dithiane and TBS protected 4-hydroxybenzaldehyde. Final
deprotection was achieved under standard TBAF conditions
(3.0 equiv TBAF, 1 M in THF, rt). Purification was achieved using
flash silica gel chromatography, gradient of 20% EtOAc/Hex to
40% EtOAc/Hex to provide C14. 1H NMR (500 MHz, CDCl3) d 7.13
(d, J = 8.1 Hz, 2H), 6.81 (d, J = 8.1 Hz, 2H), 5.13 (s, 1H), 5.00 (d,
C
18H28O3 292.2038; observed, 292.2037 [M]+.
4.6.3.3.16. 1-(2-Fluorophenyl)-1-hydroxyundecan-2-one (C19).
Prepared according to the standard procedure utilizing 2-nonyl-
1,3-dithiane and 2-fluorobenzaldehyde. Purification was achieved
using flash silica gel chromatography, gradient of hexanes to 20%
EtOAc/Hex to give C19. 1H NMR (500 MHz, CDCl3) d 7.35–7.04
(m, 4H), 5.39 (d, J = 4.4 Hz, 1H), 4.32 (d, J = 4.5 Hz, 1H), 2.47–2.23
(m, 2H), 1.55–1.42 (m, 2H), 1.34–1.06 (m, 12H), 0.84 (t,
J = 7.1 Hz, 3H). 13C NMR (125 MHz, CDCl3) d 209.1, 161.6, 159.6,
130.6, 129.0, 125.6, 124.9, 116.0, 73.3, 37.7, 32.0, 29.4, 29.3, 29.1,
23.8, 22.9, 14.3. HRMS (ESI-TOF) calcd for
C17H25FO2Na,
303.1736; observed 303.1732 [M+Na]+.
4.6.3.3.17. 1-(3-Fluorophenyl)-1-hydroxyundecan-2-one (C20).
Prepared according to the standard procedure utilizing the