K . Ueno et al.
2-(2,3,3,4,4-Pentadeutero-7,7-dimethyl-1-oxo-2,3,4,5,6,7-
hexahydro-1H-inden-2-yl)acetic acid (4)
The diester 3 (0.45 g, 1.4 mmol) was dissolved in AcOD (98 atom
% D, 1 ml, purchased from ACROS), and 20% DCl in D2O (991
atom % D, 1 ml, ACROS) was added to the solution. The mixture
was refluxed for 4 hr and diluted with H2O (50 ml), which was
extracted with EtOAc (12 ml ꢀ 5). The organic layer was washed
with brine and H2O, dried over Na2SO4 and concentrated. The
residual oil was purified by column chromatography with 30%
EtOAc in hexane to give 4 (0.29 g, 1.3 mmol, 93% yield) as a
yellow oil. 1H NMR (500 MHz, CDCl3): d 1.16 and 1.17 (each 3H, s,
Me2-7), 1.48 (2H, m H2-6), 1.70 (2H, m, H2-5), 2.39 and 2.83 (each
1H, d, J = 17.0 Hz, CH2CO2H).
Figure 4. The relative levels of deuterium incorporation at the C-3a, C-4, and C-5
positions of 5 as a function of reflux time. Compound 3 was refluxed in AcOD/DCl/
D2O for 2, 4 or 6 hr to give 4, which was subsequently reduced to give 5. The plot
displays the relative hydrogen content (obtained by integrating the peak area and
normalizing it to that of the C-8b hydrogen) at the C-3a carbon, open squares; the
C-4 carbon (2.6 ppm), filled triangles; the C-5 carbon, filled circles; and the C-3
carbon (2.3 ppm), open diamond of 5 versus reflux time. The C-3 carbon was not
deuterated.
3a,4,4,5,5-Pentadeutero-8,8-dimethyl-3,3a,4,5,6,7,8,8b-oc-
tahydro-2H-indeno[1,2-b]furan-2-one (5)
CeCl3 ꢁ 7H2O (0.98 g, 2.6 mmol) was added to a solution of 4
(0.28 g, 1.2 mmol) in MeOH (20 ml) and dissolved with stirring.
NaBH4 (0.30 g, 7.9 mmol) was carefully added to the mixture at
01C, and stirred at room temperature. After 1 hr, NaBH4 (ca 0.3 g)
was added to the mixture to reduce the unreacted 4, which was
stirred for 30 min. The resulting mixture was acidified with 20%
H2SO4 (4 ml) and diluted with H2O (150 ml). The solution was
extracted with EtOAc (18 ml ꢀ 6). The organic layer was washed
with saturated NaHCO3 (to remove the unreacted 4) and H2O,
dried over Na2SO4 and concentrated. The residual oil was
purified by column chromatography with 15% EtOAc in hexane
to give the lactone 5 (0.11 g, 0.54 mmol, 43% yield) as a pale
yellow oil. 1H NMR (500 MHz, CDCl3): d 1.08 and 1.10 (each 3H, s,
Me2-8), 1.37 and 1.47 (each 1H, m, H2-7), 1.66 (2H, m, H2-6), 2.32
and 2.79 (each 1H, d, J = 18.3 Hz, H2-3), 5.47 (1H, s, H-8b).
Table 2. Integrated 1H NMR signal intensities for the
spectra of 5 and 4 just after the samples were dissolved in
water and eight days later.
Position in 5
beforea,b
aftera,b
3a (1H)
0.0573
0.0722
0.0896
0.1441
Befored,e
0.0563
0.0560
0.0685
0.1145
0.0678
0.0496
0.2339c
0.1668
Afterd,e
0.0525
0.0455
0.0704
0.1068
4 (d 2.6, 1H)
4 (d 2.1, 1H)
5 (2H)
Position in 4
3 (1H)
4 (d 2.7, 1H)
4 (d 2.2, 1H)
5 (2H)
NaOHd,f
0.0536
0.0535
0.0628
0.1135
(3aR*,8bS*,20R*)-3a,4,4,5,5.60-hexadeutero-5-deoxystrigol
and its 2’-epimer
aThe compounds (ca 5 mg each) were first dissolved in small
amounts of MeOH, and then H2O (50 ml) was added. The 1H-
NMR spectrum of the sample labeled ‘before’ was taken
immediately after the sample was dissolved in water;
DCO2Me (981atom % D, 0.3 ml, ACROS) was added to a solution
of 5 (0.11 g, 0.50 mmol) in dry ether (2.5 ml), and sodium hydride
(40 mg) was then added to the mixture at room temperature.
The mixture was stirred at 15 hr at same temperature, and the
reaction was quenched with 1 M HCl (3 ml). The solution was
diluted to 30 ml with H2O and extracted with EtOAc (10 ml ꢀ 5).
The organic layer was washed with H2O, dried over Na2SO4 and
concentrated. The residual yellow oil was dissolved in N-methyl-
2-pyrrolidinone (1 ml). Potassium carbonate (0.14 g, 1.0 mmol)
and then 5-bromo-3-methyl-2(5H)-furanone9 (0.20 g, 1.1 mmol)
were added to the solution, which was stirred for 1 d at room
temperature. The resulting mixture was poured into 1 M HCl
(10 ml), diluted with H2O (20 ml) and extracted with EtOAc
(6 ml ꢀ 5). The organic layer was washed with H2O, dried over
Na2SO4 and concentrated. The residual oil was purified by
column chromatography with 25–30% EtOAc in hexane to give
multideuterated 1 (71 mg, 0.21 mmol, 42% yield), its 20-epimer
(48 mg, 0.14 mmol, 29% yield), and mixture of these diaster-
1
whereas, the H-NMR spectrum of the sample labeled ‘after’
was taken eight days later.
bThe values were normalized to a signal intensity of 1 for H-8b.
cThe increased signal intensity may be attributable to the
1
appearance of a new compound with a H signal at 2.1 ppm.
dThe samples were treated as described above.
eThe values were normalized to a signal intensity of 1 for H-2b.
fAfter dissolving compound 4 in water (50 ml), 1 M NaOH
(50 ml) was added.
40 mmol) was added to the mixture and stirred overnight at
401C. H2O (70 ml) was added to the resulting mixture and the
solution was extracted with EtOAc (15 ml ꢀ 5). The organic layer
was washed with saturated NH4Cl, brine and H2O, dried over
Na2SO4 and concentrated. The residual oil was purified by
column chromatography with 10–40% EtOAc in hexane to give
2 (6.6 g, 36 mmol, 91% yield) as a white solid. The 1H NMR
spectrum of 2 was consistent with the previous report.9
1
eomers (45 mg). Multideuterated 1. H NMR (500 MHz, CDCl3): d
1.10 and 1.12 (each 3H, s, Me2-8), 1.34-1.39 and 1.45–1.50 (each
1H, m, H2-7), 1.62–1.68 (2H, m, H2-6), 2.03 (3H, m, Me-40), 5.51
(1H, s, H-8b), 6.15 (1H, m, H-20), 6.93 (1H, m, H-30). Epimer of
multideuterated 1. 1H NMR (500 MHz, CDCl3): d 1.09 and 1.11
(each 3H, s, Me2-8), 1.33–1.38 and 1.45–1.50 (each 1H, m, H2-7),
1.60–1.70 (2H, m, H2-6), 2.03 (3H, m, Me-40), 5.52 (1H, s, H-8b),
6.15 (1H, m, H-20), 6.94 (1H, m, H-30).
Ethyl 2-(2-ethoxy-2-oxoethyl)-7,7-dimethyl-1-oxo-
2,3,4,5,6,7-hexahydro-1H-indene-2-carboxylate (3)
The diester 3 (0.45 g, 1.4 mmol, 48% yield) was prepared from 2
(0.48 g, 2.9 mmol) by the literature procedure.9
J. Label Compd. Radiopharm 2010, 53 763–766
Copyright r 2010 John Wiley & Sons, Ltd.