Notes
J ournal of Natural Products, 2004, Vol. 67, No. 7 1195
and pentane was subsequently added. Evaporation of the
solvent under reduced pressure afforded 3-trimethylsiloxy-
friedel-3-ene (3) (104.3 mg, 0.209 mmol, 84%): white crystals;
mp 195-197 °C. Physical and spectroscopic data of compound
3 are in agreement with literature.2
white crystals from MeOH; mp 152-155 °C (lit.7 157-158 °C);
1H NMR δ 0.91 (3H, s, Me-25); 0.95 (3H, s, Me-30); 1.00 (6H,
s, Me-26 and 29); 1.03 (3H, s, Me-27); 1,17 (3H, s, Me-28); 1.21
(3H, s, Me-24); 2.15 (3H, s, Me-23), 2.34 (2H, m, H-2), 3.63
(3H, s, O-CH3).
4r-Hyd r oxyfr ied ela n -3-on e (5). Compound 3 (100.0 mg,
0.20 mmol) was dissolved in CH2Cl2 (10 mL), and then
m-CPBA (84 mg, 0.0.37 mmol) and NaHCO3 (0.5 M, 5.5 mL)
were added. The mixture was stirred for 2 h at room temper-
3-Nor -2,4-secofr ied ela n -4-oxo-2-oic a cid (9). 3-Hydroxy-
friedel-3-en-2-one (2) (21.6 mg, 0.049 mmol) was dissolved in
CH2Cl2 (1 mL), then KMnO4 (15.5 mg, 0.049 mmol) and
benzyltriethylammonium chloride (22.5 mg, 0.049 mmol) in
CH2Cl2 were added. The mixture was stirred 24 h at room
temperature and then refluxed for 1 h. Diluted HCl (10%) was
added until the manganese oxide was destroyed. Sodium
sulfite (10%, 10 mL) was added, and the organic layer was
separated and dried with Na2SO4 to give 3-nor-2,4-seco-
friedelan-4-oxo-2-oic acid (9) (20.4 mg, 0.046 mmol, 90%): as
crystals (from EtOH); mp 213-214 °C (lit.7 215-217 °C); IR
ature. The organic layer was separated, washed with
a
saturated solution of sodium sulfite, a solution of NaHCO3,
and with distilled H2O, and then concentrated and dried (80
mg, 90.9%). The product was purified by column chromatog-
raphy (petroleum ether-CH2Cl2, 2:1) to afford 4R-hydroxy-
friedelan-3-one (5) (40 mg, 45%) and 4â-hydroxyfriedelan-3-
one (6) (12 mg, 13.5%).
4r-Hyd r oxyfr ied el-3-on e (5): white crystals (from CHCl3);
mp 268-271 °C (lit.7 269-271 °C); IR (KBr) νmax 3448 (OH),
2927, 2867 (CH2, CH3, st), 1703 (CdO), 1458, 1384 (CH2, CH3),
1107, 1071 (C-OH) cm-1; 1H NMR δ (CDCl3) 0.81 (3H, s, Me-
25), 0.88 (3H, s, Me-24), 0.95 (3H, s, Me-30), 1.00 (6H, s, Me-
26 and Me-29), 1.06 (3H, s, Me-27), 1.16 (3H, s, Me-23), 1.18
(3H, s, Me-28), 1.80 (2H, m, H-2), 2.11 (1H, dd, J 10ax1eq ) 3.3
Hz, J 10ax1ax) 12.6 Hz, H-10), 2.22 (1H, ddd, J 2eq1eq ) 2.0 Hz,
(KBr) νmax 2937, 2867, 1733 (CdO ester), 1715 (CdO) cm-1
;
1H NMR δ (CDCl3) 0.90 (3H, s, Me-25), 0.94 (3H, s, Me-30),
0.99 (3H, s, Me-26), 1.01 (3H, s, Me-27), 1.05 (3H, s, Me-29),
1.13 (3H, s, Me-24), 1.18 (3H, s, Me-28), 1.90 (1H, dd, J 1eq10ax
) 4.0 Hz, J gem ) 15.6 Hz, H-1), 2.20 (3H, s, Me-23), 2.30 (1H,
dd, J 10ax1eq ) 4.0 Hz, J 10ax1ax ) 6.6 Hz, H-10), 2.32 (1H, s,
COOH), 2.35 (1H, dd, J 1ax10ax ) 6.6 Hz, J gem ) 15.6 Hz, H-1);
13C NMR δ (CDCl3) 32.9 (C-1), 178.2 (C-2), 233.9 (C-4), 53.4
(C-5), 37.5 (C-6), 17.5 (C-7), 52.5 (C-8), 38.2 (C-9), 49.8 (C-10),
34.4 (C-11), 29.9 (C-12), 39.6 (C-13), 38.3 (C-14), 32.3 (C-15),
35.9 (C-16), 29.9 (C-17), 42.8 (C-18), 35.3 (C-19), 28.1 (C-20),
32.8 (C-21), 39.2 (C-22), 25.3 (C-23), 17.6 (C-24), 17.8 (C-25),
20.2 (C-26), 18.7 (C-27), 32.1 (C-28), 31.8 (C-29), 34.9 (C-30);
EIMS m/z 444 [M]+ (3), 426 (2), 401 (34), 342 (2), 273 (3), 205
(43), 191 (10), 149 (14), 137 (22), 123 (35), 121 (30), 109 (47),
95 (4), 81 (6), 69 (67), 55 (53), 43 (100); anal. calcd for C29H48O3,
C 78.33%, H 10.88%, found C 78.18%, H 11.27%.
J 2eq1ax ) 4.8 Hz, J gem ) 13.5 Hz, H-2), 2.98 (1H, ddd, J 2ax1eq
)
7.5 Hz, J 2ax1ax ) 13.5 Hz, J gem ) 13.5 Hz, H-2); 13C NMR δ
(CDCl3) 29.7 (C-1), 39.3 (C-2), 213.1 (C-3), 81.0 (C-4), 44.6 (C-
5), 37.1 (C-6), 21.7 (C-7), 49.3 (C-8), 37.1 (C-9), 52.4 (C-10),
35.3 (C-11), 30.5 (C-12), 39.7 (C-13), 38.2 (C-14), 32.4 (C-15),
35.8 (C-16), 29.9 (C-17), 42.8 (C-18), 33.4 (C-19), 28.2 (C-20),
32.8 (C-21), 36.0 (C-22), 16.7 (C-23), 16.9 (C-24), 18.0 (C-25),
20.3 (C-26), 18.8 (C-27), 32.1 (C-28), 31.8 (C-29), 35.1 (C-30);
EIMS m/z 442 [M]+ (17), 427 (2), 412 (7), 341 (6), 289 (2), 221
(3), 218 (17), 205 (51), 123 (56), 95 (100), 55 (80); anal. calcd
for C30H50O2, C 81.39%, H 11.38%, found C 81.42%, H 11.63%.
4â-Hyd r oxyfr ied el-3-on e (6): white crystals (from ethyl
acetate); mp 218-220 °C (lit.7 234.5-236.0 °C); 1H NMR δ
(CDCl3) 0.83 (3H, s, Me-25), 0.88 (3H, s, Me-24), 0.95 (3H, s,
Me-30), 1.00 (3H, s, Me-26), 1.01 (3H, s, Me-29), 1.06 (3H, s,
Me-27), 1.18 (3H, s, Me-28), 1.39 (3H, s, Me-23), 1.55 (2H, m,
H-1), 1.70 (1H, m, H-10), 2.50 (2H, m, H-2), 3.82 (1H, s, OH);
13C NMR δ (CDCl3) 17.6 (C-1), 39.3 (C-2), 213.0 (C-3), 81.3 (C-
4), 45.3 (C-5), 36.0 (C-6), 21.9 (C-7), 53.2 (C-8), 37.6 (C-9), 57.8
(C-10), 35.9 (C-11), 30.5 (C-12), 39.7 (C-13), 38.3 (C-14), 32.5
(C-15), 35.4 (C-16), 30.0 (C-17), 42.8 (C-18), 33.3 (C-19), 28.2
(C-20), 32.8 (C-21), 35.9 (C-22), 21.9 (C-23), 21.8 (C-24), 17.9
(C-25), 20.4 (C-26), 18.8 (C-27), 32.1 (C-28), 31.8 (C-29), 35.1
(C-30); EIMS m/z 442 [M]+ (28), 427 (2), 412 (3), 341 (4), 289
(2), 221 (2), 218 (15), 205 (57), 123 (53), 95 (100), 55 (85); anal.
calcd for C30H50O2, C 81.39%, H 11.38%, found C 81.49%, H
11.60%.
Compound 9, upon methylation with diazomethane, afforded
methyl 3-nor-2,4-secofriedelan-4-oxo-2 oate (9a ): white powder
from EtOH; mp 189-192 °C (lit.7 166-167 °C); IR (KBr) νmax
3449 (OH), 2944, 2868, 1715 (CdO, ketone) cm-1, 1701 (CdO
1
carboxylic acid); H NMR δ (CDCl3) 0.89 (3H, s, Me-25), 0.94
(3H, s, Me-30), 0.99 (3H, s, Me-26), 1.04 (3H, s, Me-27), 1.06
(3H, s, Me-29), 1.10 (3H, s, Me-24), 1.18 (3H, s, Me-28), 1.90
(1H, dd, J gem ) 16.5, J 1eq10ax ) 4.0 Hz, H-1), 2.20 (3H, s, Me-
23), 2.30 (1H, dd, J gem ) 2.1, J 1ax10ax ) 6.0 Hz, H-1), 2.40 (1H,
dd, J 10ax1ax ) 6.0; J 10ax1eq ) 4.0 Hz, H-10); 3.63 (3H, s, OMe);
13C NMR δ 32.7 (C-1), 174.6 (C-2), 214.4 (C-4), 53.6 (C-5), 37.4
(C-6), 17.5 (C-7), 52.6 (C-8), 38.1 (C-9), 49.8 (C-10), 34.3 (C-
11), 30.1 (C-12), 39.7 (C-13), 38.3 (C-14), 32.3 (C-15), 35.9 (C-
16), 29.9 (C-17), 42.8 (C-18), 35.3 (C-19), 28.2 (C-20), 32.8 (C-
21), 39.2 (C-22), 25.3 (C-23), 17.6 (C-24), 17.9 (C-25), 20.2 (C-
26), 18.8 (C-27), 32.1 (C-28), 31.8 (C-29), 35.0 (C-30); 51.7
(OCH3); EIMS m/z 458 [M]+ (4), 427 (3), 415 (44), 401 (3), 287
(3), 273 (6), 205 (56), 191 (12), 149 (22), 137 (25), 123 (40), 121
(32), 109 (51), 95 (65), 81 (43), 69 (54), 59 (100), 55 (47), 43
(70); anal. calcd for C30H50O3, C 78.55%, H 10.99%, found C
78.45%, H 10.78%.
3â,4r-Dih yd r oxyfr ied ela n e (8). 4R-Hydroxifriedel-3-one
(5) (16.8 mg, 0.038 mmol) was dissolved in CH2Cl2-MeOH (1:
1, 4 mL) and cooled to -70 °C, and NaBH4 (16.5 mg, 0.44
mmol) was added. The solution was stirred for 1 h at -70 °C
and for 3 additional hours at room temperature. Sodium
hydroxide (1 M, 10 mL) was added, and the reaction mixture
was extracted with CH2Cl2 to give 8 (6.9 mg, 0.016 mmol, 41%),
mp 240-241 °C; all the spectroscopic data were identical with
the literature.6
3,4-Secofr ied ela n -4-oxo-3-oic a cid (7). 4R-Hydroxy-
friedelan-3-one (5) (54.8 mg, 0.124 mmol) was dissolved in Et2O
(11 mL) and treated with periodic acid (37 mg, 0.16 mmol) at
0 °C with stirring for 1 h. After 5 h of further stirring at room
temperature, the reaction mixture was filtered and washed
with Et2O and the filtrate concentrated to give 3,4-secof-
riedelan-4-oxo-3-oic acid (7) (47.7 mg, 0.104 mmol, 84%): mp
141-144 °C (lit.7 205-207 °C); 1H NMR δ 0.92 (3H, s, Me-25),
0.95 (3H, s, Me-30), 1.00 (6H, s, Me-26 and Me-29), 1.03 (3H,
s, Me-27), 1.17 (3H, s, Me-28), 1.21 (3H, s, Me-24), 1.65 (1H,
m, H-10), 2.15 (3H, s, Me-23), 2.17 (1H, s, COOH), 2.39 (2H,
m, H-2); IR, 13C NMR, and EIMS are in agreement with
literature.7,8
Tu m or Cell Gr ow th Assa y. Compounds, prepared in
DMSO, were freshly diluted with cell culture medium just
prior to the assays. Final concentrations of DMSO (0.25%) did
not interfere with the cell growth. The effects of compounds
on the growth of tumor cell lines MCF-7 (breast adenocarci-
noma), NCI-H460 (non-small cell lung cancer), and SF-268
(CNS cancer) were evaluated according to the procedure
adopted by the National Cancer Institute (NCI) for the in vitro
anticancer drug screening that uses the protein-binding dye
sulforhodamine B (SRB) to assess growth inhibition. The
methodology used was the same as originally described in the
literature.9,10 Doxorubicin was used as positive control.
Ack n ow led gm en t. This work was supported by INETI,
FCT (I&D N°226/94; Ph.D. grant SFRH/BD/1456/2000), POC-
TI (QCA III), and FEDER. We would like to thank the National
Cancer Institute, Bethesda, MD, for kindly providing the
tumor cell lines. The authors are grateful to P. Puapairoj and
N. Nazareth for their help with the tumor cell growth assays.
Compound 7, upon methylation with diazomethane, afforded
the corresponding methyl 3,4-secofriedelan-4-oxo-3-oate (7a ):