D. Enders – M. Milovanovic´ · A New Lignan from Phyllanthus niruri
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dard Schlenk techniques. The chiral auxiliary (S,S)-2 was 105 (5), 77 (15). – C20H18O6 (354.35): calcd. C 67.79,
prepared according to the literature procedure [7b]. Opti- H 5.12; found C 68.05, H 5.23.
cal rotation values were measured on a Perkin-Elmer P241
(+)-Dihydrocubebin (9)
polarimeter; solvents used were of Merck UVASOL qual-
ity. Microanalyses were obtained with a Heraeus CHN-O-
To a suspension of LiAlH4 (28 mg, 0.74 mmol) in dry
THF (5 mL) at 0 C under Ar, a solution of (+)-hinokinin
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RAPID or Vario EL element analyzer. Mass spectra were ac-
quired on a Varian MAT 212 (EI, 70 eV, 1 mA) or Finnigan
MAT SSQ 7000 (CI 100 eV) spectrometer. High resolution
mass spectra were recorded on a Finnigan MAT 95 spec-
trometer. IR spectra were recorded on a Perkin-Elmer FT/IR
1760. 1H NMR (300 and 400 MHz) and 13C NMR (75 and
100 MHz) spectra were recorded on Gemini 300 or Varian
Inova 400 spectrometers with CDCl3 as a solvent and TMS
as an internal standard.
(130 mg, 0.37 mmol) in dry THF (5 mL) was slowly added
via syringe. The reaction mixture was stirred at 0 ◦C for 0.5 h
and then at r. t. for further 0.5 h. After addition of EtOAc
(20 mL) the reaction mixture was quenched with saturated
aqueous NH4Cl (10 mL) and water (5 mL). The water phase
was separated and extracted three times with EtOAc (10 mL).
The combined organic layers were dried over MgSO4 and
evaporated in vacuum. The crude product was purified by
column chromatography (Et2O) to give (+)-dihydrocubebin
Compounds 3, 4, 5, and 6 were prepared following the
same procedure and experimental conditions as described
previously [7k, 7g, 7i].
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(9) (119 mg, 90 %) as colourless cubes. – M. p. 102 C
(lit. [11]: 103 – 104 ◦C). – IR (KBr): ν = 3852 (s), 3742 (s),
3681 (m), 3430 (m), 3337 (m), 2361 (s), 2339 (s), 1700 (s),
1650 (s), 1505 (s), 1246 (s), 1036 (s), 669 (m). – 1H NMR
(300 MHz, CDCl3): δ = 1.83 (m, 2H, 2 × CH2CHCH2),
2.60 (dd, J = 13.6, 5.6 Hz, 2H, 2 × CCHH), 2.73 (dd, J =
13.6, 8.6 Hz, 2H, 2 × CCHH), 3.48 (dd, J = 11.1, 3.9 Hz,
2H, 2 × CHHOH), 3.76 (d, J = 11.1 Hz, 2H, 2 × CHHOH),
3.83 (s, 2H, 2 × CH2OH), 5.90 (s, 4H, 2 × OCH2O), 6.59
(d, J = 7.9 Hz, 2H, arom. CH), 6.63 (s, 2H, arom. CH),
6.70 (d, J = 7.9 Hz, 2H, arom. CH) ppm. – 13C NMR
(75 MHz, CDCl3): δ = 35.89 (CCH2), 44.26 (CH2CHCH2),
60.02 (CH2OH), 100.77 (OCH2O), 108.09, 109.33, 121.86
(arom. CH), 134.36, 145.69, 147.55 (arom. C) ppm. – MS
(EI, 70 eV): m/z (%) = 359 (7) [M+1]+, 358 (38) M+,
340 (14), 203 (22), 191 (10), 187 (14), 174 (5), 172 (8),
160 (6), 136 (34), 135 (100), 130 (5), 77 (10). – C20H22O6
(358.39): calcd. C 67.03, H 6.19; found C 67.27, H 6.12.
(+)-Hinokinin (8)
To a solution of ketone 6 (354 mg, 0.96 mmol) in CH2Cl2
(30 mL) was added NaBH4 (0.12 g, 3.04 mmol) and MeOH
(15 mL). After 2 h the reaction mixture was diluted with
CH2Cl2 (30 mL) and water (10 mL). The aqueous phase
was extracted three times with CH2Cl2 (15 mL). The com-
bined organic layers were dried over MgSO4 and evaporated
in vacuum. The crude product was directly used for the next
step. The epimeric mixture of alcohol 7 (356 mg, 0.96 mmol)
was dissolved in dry ethanol (60 mL) and two drops of aque-
ous HClO4 were added. The mixture was hydrogenated us-
ing Pd/C (60 mg) as a catalyst at 4 atm H2 pressure. Af-
ter 48 h, the solution was neutralized with Na2CO3 and the
catalyst was filtered off. The solvent was evaporated in vac-
uum and the crude product was purified by column chro-
matography (Et2O : pentane = 1 : 1) to give 299 mg (88 %)
of (+)-hinokinin (8) as a colourless syrup. – IR (CHCl3):
ν = 2903 (s), 2362 (m), 1768 (s, C=O), 1492 (s), 1443 (s),
Cubebin dimethyl ether (1)
To a stirred solution of (+)-dihydrocubebin (9) (60 mg,
1247 (s), 1191 (s), 1038 (s), 928 (s), 811 (m), 756 (m), 0.20 mmol) in dry THF (5 mL) methyl iodide (123 mg,
668 (m). – 1H NMR (400 MHz, CDCl3): δ = 2.41 – 2.62 0.86 mmol), sodium hydride (370 mg, 9.20 mmol, 60 % dis-
(m, 4H, OCH2CHCH2, OCH2CHCH2, OCCHCH2), 2.84 persion in oil) and a second portion of methyl iodide (68 mg,
(dd, J = 14.0, 7.1 Hz, 1H, OCCHCHH), 2.98 (dd, J = 14.0, 0.48 mmol) were added. After 2.5 h at r. t., the mixture was
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4.9 Hz, 1H, OCCHCHH), 3.85 (dd, J = 9.0, 7.4 Hz, 1H, cooled to 0 C and methanol (5 mL) was added. Concen-
OCHHCH), 4.12 (dd, J = 9.0, 7.1 Hz, 1H, OCHHCH), 5.93 tration under reduced pressure and flash chromatography of
(s, 4H, 2 × OCH2O), 6.46 (m, 2H, arom. CH), 6.60 (dd, the crude compound (Et2O : pentane = 1 : 3) afforded 76 mg
J = 7.9, 1.6 Hz, 1H, arom. CH), 6.62 (d, J = 1.6 Hz, 1H, (98 %) of cubebin dimethyl ether (1) as a colourless oil. – IR
arom. CH), 6.69 (d, J = 8.2 Hz, 1H, arom. CH), 6.73 (d, (CHCl3): ν = 2889 (s), 2356 (s), 1493 (s), 1477 (s), 1246 (s),
J = 7.7 Hz, 1H, arom. CH) ppm. – 13C NMR (100 MHz, 1195 (m), 1111 (s), 1040 (s), 933 (m), 866 (s), 808 (m),
CDCl3): δ = 34.76 (CH2CHCO), 38.29 (CH2CHCH2O), 758 (s). – 1H NMR (400 MHz, CDCl3): δ = 2.01 (m, 2H, 2×
41.22 (CH2CHCH2), 46.40 (CH2CHCO), 71.02 (CHCH2O), CH2CHCH2), 2.56 (dd, J = 13.7, 8.2 Hz, 2H, 2 × CCHH),
100.86 (OCH2O), 108.10, 108.17, 108.64, 109.26, 121.35, 2.65 (dd, J = 13.7, 6.0 Hz, 2H, 2 × CCHH), 3.28 (s, 6H,
122.03 (arom. CH), 131.13, 131.41, 146.12, 146.24, 147.63, 2 × CH3O), 3.28 (dd, J = 9.9, 4.9 Hz, 4H, 2 × CH3OCH2),
147.66 (arom. C), 178.14 (CO) ppm. – MS (EI, 70 eV): m/z 5.91 (s, 4H, 2 × OCH2O), 6.56 (dd, J = 7.9, 1.6 Hz, 4H,
(%) = 355 (15) [M+1]+, 354 (67) M+, 219 (6), 217 (16), arom. CH), 6.70 (d, J = 7.9 Hz, 2H, arom. CH) ppm. –
172 (6), 161 (8), 160 (7), 135 (33), 134 (100), 130 (7), 13C NMR (100 MHz, CDCl3): δ = 34.81 (CCH2), 40.89
Unauthenticated
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