K. M. Lovell et al. / Bioorg. Med. Chem. 20 (2012) 3100–3110
3107
2.23–2.09 (m, 6H), 1.84–1.56 (m, 4H), 1.47 (s, 3H), 1.09 (s, 3H). 13
C
0.055 g (43.9%) isolated as a white solid, mp = 124–127 °C. 1H
NMR (500 MHz, CDCl3) d 8.25 (t, J = 1.4 Hz, 1H), 8.18–8.14 (m,
1H), 7.92–7.88 (m, 1H), 7.66 (t, J = 7.8 Hz, 1H), 5.79 (t, J = 8.3 Hz,
1H), 5.18–5.10 (m, 1H), 3.72 (s, 3H), 2.80–2.71 (m, 1H), 2.58 (dd,
J = 7.9, 13.7 Hz, 1H), 2.35–2.26 (m, 2H), 2.21 (s, 1H), 2.20–2.08
(m, 5H), 1.82–1.52 (m, 4H), 1.48 (s, 3H), 1.10 (s, 3H). 13C NMR
NMR (126 MHz, CDCl3) d 202.20, 200.58, 171.74, 170.98, 170.06,
163.70, 137.98, 129.64, 119.97, 119.25, 116.55, 75.08, 74.43,
64.96, 53.46, 52.22, 49.49, 42.23, 38.94, 37.93, 35.83, 30.88, 20.79,
18.49, 16.82, 16.22. HRMS (m/z): [MÀH] calcd for C26H29O9,
485.1812; found 485.1808. HPLC tR = 6.986 min; purity = 96.16%.
(126 MHz, CDCl3)
d 202.11, 193.43, 171.71, 170.42, 170.09,
5.4.6. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-(3-hy-
droxybenzoyl)-6a,10b-dimethyl-4,10-dioxododecahydro-1H-
benzo[f]isochromene-7-carboxylate (17)
137.18, 134.85, 133.13, 132.96, 130.28, 117.76, 113.99, 75.65,
75.05, 64.78, 53.49, 52.22, 50.01, 42.18, 37.90, 37.64, 35.72,
30.88, 20.80, 18.41, 16.77, 16.30. HRMS (m/z): [MÀH] calcd for
Compound 17 was synthesized from compound 11 using the
general procedure and 3-hydroxyphenylboronic acid to afford
0.033 g (28.9%) isolated as a white solid, mp = 131–135 °C. 1H
NMR (500 MHz, CDCl3) d 7.23 (t, J = 7.9 Hz, 1H), 7.16–7.12 (m,
1H), 7.10 (d, J = 7.8 Hz, 1H), 6.96 (s, 1H), 6.92 (dd, J = 1.9, 8.1 Hz,
1H), 5.78 (dd, J = 6.9, 10.2 Hz, 1H), 5.17 (dd, J = 8.0, 12.1 Hz, 1H),
3.73 (d, J = 2.0, 3H), 3.00–2.89 (m, 2H), 2.82 (dd, J = 10.3, 13.4 Hz,
1H), 2.37–2.25 (m, 2H), 2.21 (s, 3H), 2.19–2.09 (m, 2H), 1.84 (d,
J = 9.8 Hz, 1H), 1.78–1.62 (m, 3H), 1.48 (s, 3H), 1.07 (s, 3H). 13C
NMR (126 MHz, CDCl3) d 202.84, 196.51, 172.04, 171.73, 171.59,
157.11, 133.45, 130.47, 122.70, 120.61, 114.06, 76.42, 75.37,
63.95, 52.94, 52.19, 48.83, 42.71, 38.75, 37.79, 35.85, 30.81, 21.00,
18.82, 17.22, 16.13. HRMS (m/z): [MÀH] calcd for C26H29O9,
485.1812; found 485.1801. HPLC tR = 4.286 min; purity = 99.66%.
C27H28NO8, 494.1815; found 494.1806. HPLC tR = 6.510 min;
purity = 95.94%.
5.4.10. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-6a,10b-
dimethyl-4,10-dioxo-2-(3-(tri-fluoromethoxy)benzoyl)dodeca-
hydro-1H-benzo[f]isochromene-7-carboxylate (21)
Compound 21 was synthesized from compound 11 using the
general procedure and 3-(trifluoromethoxy)-phenylboronic acid
to afford 0.038 g (24.3%) isolated as a white solid, mp = 92–
94 °C. 1H NMR (500 MHz, CDCl3) d 7.86–7.80 (m, 2H), 7.56 (t,
J = 8.0 Hz, 1H), 7.48 (d, J = 7.2 Hz, 1H), 5.81 (t, J = 8.3 Hz, 1H),
5.16–5.09 (m, 1H), 3.72 (s, 3H), 2.78–2.69 (m, 1H), 2.62 (dd,
J = 8.3, 13.6 Hz, 1H), 2.29 (dd, J = 7.2, 13.5 Hz, 2H), 2.19 (s, 1H),
2.18–2.09 (m, 5H), 1.77 (d, J = 13.2 Hz, 1H), 1.71–1.53 (m, 3H),
1.47 (s, 3H), 1.09 (s, 3H). 13C NMR (126 MHz, CDCl3) d 202.15,
5.4.7. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-(4-hy-
droxybenzoyl)-6a,10b-dimethyl-4,10-dioxododecahydro-1H-
benzo[f]isochromene-7-carboxylate (18)
Compound 18 was synthesized from compound 11 using the
general procedure and 4-hydroxyphenylboronic acid to afford
0.092 g (68.0%) isolated as a white solid, mp = 232–236 °C. 1H
3
193.97, 171.75, 170.72, 170.07, 150.00 (q JCF = 1.97), 135.62,
130.91, 127.43, 126.77, 121.56, 120.56 (q JCF = 258.18), 75.62,
75.06, 64.91, 53.48, 52.21, 49.77, 42.19, 38.03, 37.91, 35.76,
30.89, 20.79, 18.44, 16.88, 16.27. HRMS (m/z): [M+Na] calcd for
C27H29F3O9Na, 577.1661; found 577.1621. HPLC tR = 15.925 min;
NMR (500 MHz, CDCl3)
d 7.82 (d, J = 8.8 Hz, 2H), 6.85 (d,
purity = 97.74%.
J = 8.8 Hz, 2H), 6.16 (s, 1H), 5.80 (t, J = 8.3 Hz, 1H), 5.13–5.08 (m,
1H), 3.72 (s, 3H), 2.72 (d, J = 7.7 Hz, 1H), 2.62 (dd, J = 8.7, 13.6 Hz,
1H), 2.30 (d, J = 10.7 Hz, 2H), 2.20 (s, 1H), 2.17 (s, 5H), 1.79–1.52
(m, 4H), 1.45 (s, 3H), 1.08 (s, 3H). 13C NMR (126 MHz, CDCl3) d
202.27, 193.59, 171.80, 171.60, 170.41, 161.34, 131.84, 126.60,
116.09, 77.44, 75.25, 65.01, 53.45, 52.21, 49.43, 42.25, 38.48,
37.94, 35.71, 30.88, 20.85, 18.46, 17.06, 16.23. HRMS (m/z):
5.4.11. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-6a,10b-
dimethyl-4,10-dioxo-2-(3-(tri-fluoromethyl)benzoyl)dodecahy-
dro-1H-benzo[f]isochromene-7-carboxylate (22)
Compound 22 was synthesized from compound 11 using the
general procedure and 3-(trifluoromethyl)phenylboronic acid to
afford 0.044 g (38.8%) isolated as an off-white solid, mp = 94–
97 °C. 1H NMR (500 MHz, CDCl3) d 8.23 (s, 1H), 8.10 (d, J = 7.9 Hz,
1H), 7.88 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.8 Hz, 1H), 5.84 (t,
J = 8.3 Hz, 1H), 5.16–5.10 (m, 1H), 3.72 (s, 3H), 2.79–2.70 (m, 1H),
2.61 (dd, J = 8.2, 13.6 Hz, 1H), 2.29 (dd, J = 7.5, 13.5 Hz, 2H), 2.20
(s, 1H), 2.19–2.08 (m, 5H), 1.77 (d, J = 13.2 Hz, 1H), 1.75–1.53 (m,
3H), 1.48 (s, 3H), 1.09 (s, 3H). 13C NMR (126 MHz, CDCl3) d
202.15, 194.16, 171.74, 170.66, 170.08, 134.49, 132.33, 132.05 (q,
MÀH] calcd for
C26H29O9, 485.1812; found 485.1783. HPLC
tR = 4.624 min; purity = 95.63%.
5.4.8. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-(3-car-
bamoylbenzoyl)-6a,10b-dimethyl-4,10-dioxododecahydro-1H-
benzo[f]isochromene-7-carboxylate (19)
Compound 19 was synthesized from compound 11 using the
general procedure and 3-aminocarbonylphenylboronic acid to af-
ford 0.062 g (37.8%) isolated as a white solid, mp = 148–152 °C.
1H NMR (500 MHz, CDCl3) d 8.30 (s, 1H), 8.07 (d, J = 7.8 Hz, 1H),
8.02 (d, J = 7.9 Hz, 1H), 7.58 (t, J = 7.8 Hz, 1H), 6.52–6.31 (m, 1H),
5.88 (t, J = 8.4 Hz, 1H), 5.84–5.65 (m, 1H), 5.18–5.11 (m, 1H), 3.72
(s, 3H), 2.82–2.73 (m, 1H), 2.65 (dd, J = 8.4, 13.6 Hz, 1H), 2.28
(dd, J = 7.3, 13.3 Hz, 3H), 2.20–2.09 (m, 5H), 1.78 (d, J = 13.0 Hz,
1H), 1.75–1.54 (m, 3H), 1.47 (s, 3H), 1.09 (s, 3H). 13C NMR
3
2JCF =33.11 Hz), 130.87 (q, JCF = 3.41 Hz), 129.97, 126.18 (q,
3JCF = 3.84 Hz), 123.63 (q, JCF = 272.85 Hz), 75.56, 75.06, 64.91,
53.49, 52.22, 49.84, 42.20, 37.92, 37.86, 35.75, 30.90, 20.80,
18.44, 16.90, 16.28. HRMS (m/z): [M+Na] calcd for C27H29F3O8Na,
561.1712; found 561.1670. HPLC tR = 5.799 min; purity = 95.0% as
determined using a Phenomenex Luna column (250 Â 4.5 mm,
5 lm).
(126 MHz, CDCl3)
d 202.32, 194.95, 171.81, 170.95, 170.22,
168.05, 134.59, 133.96, 133.38, 132.26, 129.75, 127.79, 75.66,
75.18, 64.74, 53.40, 52.20, 49.71, 42.24, 38.11, 37.91, 35.78,
30.90, 20.82, 18.49, 16.87, 16.27. HRMS (m/z): [M+Na] calcd for
5.4.12. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-(fu-
ran-2-carbonyl)-6a,10b-dimethyl-4,10-dioxododecahydro-1H-
benzo[f]isochromene-7-carboxylate (23)
C27H31NO9Na, 536.1897; found 536.1901. HPLC tR = 3.465 min;
Compound 23 was synthesized from compound 11 using the
general procedure and 2-furanylboronic acid to afford 0.109 g
(84.6%) isolated as a white solid, mp = 207–209 °C. HRMS (m/z):
purity = 96.22% using 40% CH3CN:60% H2O as the mobile phase.
5.4.9. (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-(3-cya-
nobenzoyl)-6a,10b-dimethyl-4,10-dioxododecahydro-1H-ben-
zo[f]isochromene-7-carboxylate (20)
Compound 20 was synthesized from compound 11 using the
general procedure and 3-cyanophenylboronic acid to afford
[M+H] calcd for
C24H29O9, 461.1812; found 461.1796. HPLC
tR = 13.29 min; purity = 97.83% using 40% CH3CN:60% H2O as the
mobile phase. The 1H NMR and 13C NMR spectra were in agree-
ment with that previously reported.32