New Techniques of Structure Elucidation for Sesquiterpenes
293
Three new dihydro-β-agarofurans named bilocularins A–C (227–229) were
isolated from the dichloromethane extracts of the leaves of the Australian rainforest tree Maytenus bilocularis. Their structural elucidation was carried out through
the analysis of NMR and mass spectrometric data, while the relative configuration was proposed from ROESY experiments. The absolute configurations of
bilocularins A (227) and B (228) were determined as (1S,4R,5S,6R,7R,8R,9S,10S)
and (1S,4R,5S,6R,7R,9S,10S), respectively, using the anomalous dispersion effects
measured in their single-crystal X-ray diffraction analyses [105]. The Flack parameter of 5 was 0.02(6), by considering of a total of 1955 Bijvoet pairs, while that
for 6 was 0.05(6) with a total of 1825 Bijvoet pairs. The absolute configuration of
bilocularin C (229) was assigned as (1S,4R,5S,6R,7S,8R,9S,10S) based on biosynthesis considerations and comparison of chiroptical data. Bilocularins A (227) and B
(228) each displayed a biological effect comparable to the drug efflux pump inhibitor
verapamil in reversing drug resistance of a the CEM/VCR R human leukemia cell
line [105].
O
OR
1
AcO
OBz
OAc
OR
2
O
OAc
AcO
OBz
OAc
O
228 (bilocularin B)
227 R
1 = Ac, R
2 = H (bilocularin A)
229 R
1 = H, R
2 = Ac (bilocularin C)
1
3
5
9
7
11
12
13
14
15
The chemical examination of extracts of Eupatorium chinense, a shrub of the
Asteraceae family collected at Changyang, People’s Republic of China, gave ten
new germacrane-type sesquiterpene lactones (230–239) [106]. The absolute configuration of compound 230, named eupachinsin, was determined as (2R,3R,6R,7R,8R)
by single-crystal X-ray diffraction analysis and the calculation of the Flack parameter
0.07(7) determined with 1701 quotients. The relative stereochemistry for compounds
231–239 was determined by the similarity of the ROESY correlations and coupling
constants as compared to those of 230. The ECD spectra of 230–239 were found to
be very similar, showing a weak positive Cotton effect around 250 nm and an intense
negative effect around 210 nm, mainly attributed to the α,β-unsaturated lactone chromophore containing the exocyclic double bond. The resemblance observed in the
ECD spectra of these compounds indicated that compounds 231–239 have the same
absolute configuration at C-6 and C-7 as compound 230. Compounds 232 and 233
showed cytotoxicity against the MDA-MB-231 human breast cancer cell line, with
IC 50 values of 0.8 and 3.4 μM, respectively, while 232–234 showed cytotoxic activity
against a human hepatocellular carcinoma cell line (HepG2), with IC 50 values ranging
from 3.6 to 7.6 μM [106].
293
Three new dihydro-β-agarofurans named bilocularins A–C (227–229) were
isolated from the dichloromethane extracts of the leaves of the Australian rainforest tree Maytenus bilocularis. Their structural elucidation was carried out through
the analysis of NMR and mass spectrometric data, while the relative configuration was proposed from ROESY experiments. The absolute configurations of
bilocularins A (227) and B (228) were determined as (1S,4R,5S,6R,7R,8R,9S,10S)
and (1S,4R,5S,6R,7R,9S,10S), respectively, using the anomalous dispersion effects
measured in their single-crystal X-ray diffraction analyses [105]. The Flack parameter of 5 was 0.02(6), by considering of a total of 1955 Bijvoet pairs, while that
for 6 was 0.05(6) with a total of 1825 Bijvoet pairs. The absolute configuration of
bilocularin C (229) was assigned as (1S,4R,5S,6R,7S,8R,9S,10S) based on biosynthesis considerations and comparison of chiroptical data. Bilocularins A (227) and B
(228) each displayed a biological effect comparable to the drug efflux pump inhibitor
verapamil in reversing drug resistance of a the CEM/VCR R human leukemia cell
line [105].
O
OR
1
AcO
OBz
OAc
OR
2
O
OAc
AcO
OBz
OAc
O
228 (bilocularin B)
227 R
1 = Ac, R
2 = H (bilocularin A)
229 R
1 = H, R
2 = Ac (bilocularin C)
1
3
5
9
7
11
12
13
14
15
The chemical examination of extracts of Eupatorium chinense, a shrub of the
Asteraceae family collected at Changyang, People’s Republic of China, gave ten
new germacrane-type sesquiterpene lactones (230–239) [106]. The absolute configuration of compound 230, named eupachinsin, was determined as (2R,3R,6R,7R,8R)
by single-crystal X-ray diffraction analysis and the calculation of the Flack parameter
0.07(7) determined with 1701 quotients. The relative stereochemistry for compounds
231–239 was determined by the similarity of the ROESY correlations and coupling
constants as compared to those of 230. The ECD spectra of 230–239 were found to
be very similar, showing a weak positive Cotton effect around 250 nm and an intense
negative effect around 210 nm, mainly attributed to the α,β-unsaturated lactone chromophore containing the exocyclic double bond. The resemblance observed in the
ECD spectra of these compounds indicated that compounds 231–239 have the same
absolute configuration at C-6 and C-7 as compound 230. Compounds 232 and 233
showed cytotoxicity against the MDA-MB-231 human breast cancer cell line, with
IC 50 values of 0.8 and 3.4 μM, respectively, while 232–234 showed cytotoxic activity
against a human hepatocellular carcinoma cell line (HepG2), with IC 50 values ranging
from 3.6 to 7.6 μM [106].