Synthesis and absolute configuration of (S)-(-)- and (R)-(+)-2,3- dihydro-2-(1-methylethenyl)-6-methoxybenzofuran

Article abstract of DOI:10.1021/np980521o

Resolution of racemic 2,3-dihydro-2-carboxy-6-methoxybenzofuran (2) by recrystallizations of diastereomeric salts prepared with (S)-(-)-α- methylbenzylamine and (R)-(+)-α-methylbenzylamine gave the starting materials for the four-step total syntheses of (S)-(-)-2,3-dihydro-2-(1- methylethenyl)-6-methoxybenzofuran (1a) and (R)-(+)-2,3-dihydro-2-(1- methylethenyl)-6-methoxybenzofuran (1b). Their absolute configuration was established by chemical correlation.

Full text of DOI:10.1021/np980521o

J . Nat. Prod. 1999, 62, 1085-1087
1085
Syn th esis a n d Absolu te Con figu r a tion of (S)-(-)- a n d
(R)-(+)-2,3-Dih yd r o-2-(1-m eth yleth en yl)-6-m eth oxyben zofu r a n
Ricardo Tovar-Miranda,† Rau´l Corte´s-Garc´ıa,† Luis Rau´l Trinidad-Nino,† and Pedro J oseph-Nathan*,‡
Instituto de Ciencias Ba´sicas, Universidad Veracruzana, Apartado Postal 575, Xalapa, Ver., 91000 Me´xico, and
Departamento de Quı´mica del Centro de Investigacio´n y de Estudios Avanzados, Instituto Polite´cnico Nacional,
Apartado 14-740, Me´xico, D.F., 07000 Me´xico
Received November 18, 1998
Resolution of racemic 2,3-dihydro-2-carboxy-6-methoxybenzofuran (2) by recrystallizations of diastereo-
meric salts prepared with (S)-(-)-R-methylbenzylamine and (R)-(+)-R-methylbenzylamine gave the starting
materials for the four-step total syntheses of (S)-(-)-2,3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran
(1a ) and (R)-(+)-2,3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran (1b). Their absolute configuration
was established by chemical correlation.
Sch em e 1. Synthetic Route for (S)-(-)-1a and (R)-(+)-1b
A Chemical Abstracts search for (S)-(-)-2,3-dihydro-2-
(1-methylethenyl)-6-methoxybenzofuran (1a ) and (R)-(+)-
2,3-dihydro-2-(1-methylethenyl)-6-methoxybenzofuran (1b)
revealed that these compounds appear in indexes1,2 as
natural products isolated from Eupatorium gruppe3 and
Eupatorium aschembornianum,4 respectively. When one
carefully looks at the papers referenced, it becomes clear
that the absolute configuration of the (S)-(-)-1a isomer was
suggested tentatively based on analogy to other com-
pounds5 and that the absolute stereochemistry of the (R)-
(+)-1b isomer derives just from the drawing of the mol-
ecule; that is, the authors4 indicate that their compound
is equal to the one published previously3 but have drawn
the reverse stereochemistry. Neither of these papers3,4
reports optical activity data for either isomer. Therefore,
we report here the synthesis and the absolute configuration
of both (S)-(-)-1a and (R)-(+)-1b.
Resu lts a n d Discu ssion
The preparation of (S)-(-)-1a and (R)-(+)-1b is shown
in Scheme 1 using dihydrobenzofuran 26 as the starting
material. This racemic molecule was resolved using the
commercially available enantiomers of R-methylbenzyl-
amine (R-MBA). Thus, compound 2 was dissolved in
acetone, and one equivalent of (S)-(-)-R-MBA was added.
The resultant precipitate was recrystallized several times
from acetone to give the enantiomerically pure salt (-)-
3a , mp 164-166 °C and [R]D -72.6°. The mother liquors
were concentrated and treated with hydrochloric acid to
afford the acid 2, which, in turn, was treated with (R)-(+)-
R-MBA to give the enantiomerically pure salt (+)-3b, mp
165-166 °C and [R]D +73°. Treatment of (-)-3a with
diluted hydrochloric acid yielded acid (-)-2a as an amor-
phous solid, 122-123 °C and [R]D -75°, while treatment
of (+)-3b with diluted hydrochloric acid gave (+)-2b with
[R]D +75.5°.
Each acid, (-)-2a and (+)-2b, was subjected to the
following sequence of reactions: Treatment of (-)-2a /(+)-
2b with methanol and p-toluenesulfonic acid gave the
methyl esters7 (-)-4a /(+)-4b, which were treated with
methylmagnesium iodide, yielding the tertiary alcohols (+)-
5a /(-)-5b. Acetylation of (+)-5a /(-)-5b in boiling acetic
anhydride afforded the corresponding acetates (+)-6a /
(-)-6b as amorphous solids. Fast pyrolysis8 of (+)-6a at
330 °C for 10 min afforded 2-isopropyl-6-methoxybenzo-
furan (7) and the desired (-)-2,3-dihydro-2-(1-methyl-
ethenyl)-6-methoxybenzofuran (1a )9,10 in a 1:8 ratio. When
(+)-6a was heated for longer periods at 330 °C, compound
7 became the main product. Similarly, treatment of (-)-
6b under the same conditions gave (+)-1b and 7, also in
an 8:1 ratio. Comparison of spectroscopic data of (-)-1a
* To whom correspondence should be addressed. Tel.: +52 5747-7112.
Fax: +52 5747-7113. E-mail: pjoseph@nathan.chem.cinvestav.mx.
† Universidad Veracruzana.
‡ Instituto Polite´cnico Nacional.
10.1021/np980521o CCC: $18.00
© 1999 American Chemical Society and American Society of Pharmacognosy
Published on Web 08/10/1999

1086 J ournal of Natural Products, 1999, Vol. 62, No. 8
Tovar-Miranda et al.
quors remaining from the above recrystallizations were con-
centrated, treated with 12 mL of 5 N HCl and extracted with
EtOAc. The organic layer was washed with H2O, dried, and
concentrated under vacuum to give a brown solid that was
dissolved in CH2Cl2 and treated with activated carbon. After
filtration of the charcoal and evaporation of the filtrate, a white
solid was obtained, which was dissolved in Me2CO, and 1 equiv
of (R)-(+)-R-MBA was added, as in the previous case. The white
crystalline precipitate formed was filtered, washed with
Me2CO, and, after four recrystallizations from Me2CO, gave 5
g of (R)-(+)-3b as a white cotton-like material, mp 165-166
°C; [R]D +73° (c 3.0, MeOH).
(S)-(-)-2,3-Dih yd r o-2-ca r b oxy-6-m et h oxyb en zofu r a n
(2a ). A vigorously stirred mixture of the salt (-)-3a (5 g), H2O
(50 mL), and EtOAc (50 mL) was cooled in an ice-H2O bath
and acidified dropwise with 5.3 mL of 5 N HCl over a period
of 10 min. The separated organic layer was washed with H2O,
dried, and evaporated under vacuum to afford (S)-(-)-2a (3 g)
as a white amorphous solid: mp 122-123 °C; [R]D -75° (c 0.92,
CHCl3); UV (EtOH) λmax (log ꢀ) 201 (1.64), 286 (0.66) nm; IR
(KBr) νmax 3502, 1710, 1240 cm-1; 1H NMR (CDCl3, 300 MHz)
δ 10.55 (1H, s, COOH), 7.03 (1H, d, J ) 8.2 Hz, H-4), 6.50
(1H, d, J ) 2.3 Hz, H-7), 6.45 (1H, dd, J ) 8.2, 2.3 Hz, H-5),
5.23 (1H, dd, J ) 10.8, 6.4 Hz, H-2), 3.75 (3H, s, OCH3), 3.53
(1H, dd, J ) 15.5, 10.8 Hz, H-3â), 3.31 (1H, dd, J ) 15.5, 6.4
Hz, H-3R); 13C NMR (CDCl3, 74.5 MHz) δ 176.72 (s, C-1′),
160.54 (s, C-6), 159.98 (s, C-7a), 124.66 (d, C-4), 116.08 (s,
C-3a), 107.30 (d, C-5), 96.47 (d, C-7), 79.09 (d, C-2), 55.50 (q,
OCH3), 33.24 (t, C-3); EIMS m/ z 194 [M]+ (98), 176 (38), 148
(100), 133 (34).
obtained by us with those reported for the natural product
isolated from E. gruppe3 and E. aschembornianum4 re-
vealed that they are identical.
The absolute configuration of (-)-4a and (+)-4b was
established by chemical correlation using the (S)-(-)-
methyl coumarancarboxylate (8) of known configuration,11
which was debenzylated by catalytic hydrogenolysis12 in
the presence of palladium on charcoal in ethanol to give
the phenol (S)-(-)-9. Treatment of (S)-(-)-9 with iodo-
methane in acetone and K2CO3 afforded (S)-(-)-4a . Com-
parison of the spectroscopic and optical activity data of (S)-
(-)-4a obtained from methyl ester (S)-(-)-8 with that
prepared from salt (-)-3a revealed that they are identical.
Therefore, the series of compounds prepared from salt (-)-
3a have the S absolute configuration, while those prepared
from (+)-3b are R.
The two protons at C-3 were stereochemically assigned
after generating minimum energy structures using MMX
force-field calculations as implemented in the PCMODEL
program13 V4.00. The obtained dihedral angles for the
dihydrofuran ring protons were used to estimate vicinal
coupling constants using Karplus-type calculations by
means of a computer program we developed almost a
decade ago.14 The agreement between experimental and
estimated values allowed individual assignment of H-3R
and H-3â for 2a , 4a , 6a , and 9. In these four cases H-3â
has a large coupling constant due to the trans orientation
of H-2 and H-3â, in which H-3R has a smaller coupling
constant due to the cis orientation of H-2 and H-3R.
Because, in the latter four cases, H-3â appears at higher
fields than H-3R, we assigned by chemical-shift analogy
the two protons at C-3 in 1a , where J 2,3R ) J 2,3â ) 8.8 Hz.
Finally, in the case of 5a , instead of the ABX spin-spin
system15 shown in all previously discussed 1H NMR
spectra, the dihydrofuran protons appear as an AX2
system,15 characterized by chemical shifts and a single
vicinal coupling constant, due to chemical shift coincidence
of H-3R and H-3â. To gain evidence supporting a similar
conformation of the five-membered 2,3-dihydrofuran ring
(R)-(+)-2,3-Dih yd r o-2-ca r b oxy-6-m et h oxyb en zofu r a n
(2b). Using the previous procedure, acidification of 5 g of salt
(+)-3b gave (R)-(+)-2b (2.9 g) as a white amorphous solid: mp
121-122 °C; [R]D +75.5° (c 2.9, CHCl3).
(S)-(-)-2,3-Dih yd r o-2-ca r boxym eth yl-6-m eth oxyben zo-
fu r a n (4a ). A solution of (S)-(-)-2a (3 g, 15.5 mmol) and
p-toluenesulfonic acid (100 mg) in 30 mL of anhydrous MeOH
was refluxed for 3 h. The solution was concentrated to a small
volume under vacuum and extracted with EtOAc. The organic
layer was washed with 10% aqueous K2CO3 (2 × 30 mL) and
H2O and dried. Evaporation of the solvent under reduced
pressure yielded (S)-(-)-4a (3.04 g, 95%) as a colorless oil: bp
90 °C/0.04 mmHg; [R]D -52.2° (c 4.4, CHCl3); UV (EtOH) λmax
(log ꢀ) 202 (1.50), 286 (0.68) nm; IR (dry film) νmax 1742, 1148
1
in 5a , the H NMR spectrum was determined in benzene-
1
cm-1; H NMR (CDCl3, 300 MHz) δ 7.03 (1H, d, J ) 8.2 Hz,
d6, where it gave an ABX system, the pertinent data being
H-4), 6.50 (1H, d, J ) 2.3 Hz, H-7), 6.44 (1H, dd, J ) 8.2, 2.3
Hz, H-5), 5.22 (1H, dd, J ) 10.5, 6.8 Hz, H-2), 3.80 (3H, s,
OCH3), 3.76 (3H, s, OCH3), 3.49 (1H, dd, J ) 15.4, 10.5 Hz,
H-3â), 3.30 (1H, dd, J ) 15.4, 6.8 Hz, H-3R); 13C NMR (CDCl3,
74.5 MHz) δ 171.66 (s, C-1′), 160.61 (s, C-6), 160.30 (s, C-7a),
124.66 (d, C-4), 116.48 (s, C-3a), 107.05 (d, C-5), 96.50 (d, C-7),
79.84 (d, C-2), 55.53 (q, OCH3), 52.54 (q, OCH3), 33.24 (t, C-3);
EIMS m/ s 208 [M]+ (100), 176 (81), 148 (99), 121 (68).
(R)-(+)-2,3-Dih yd r o-2-ca r b oxym et h yl-6-m et h oxyb en -
zofu r a n (4b). The ester (R)-(+)-4b (2.95 g, 95%) was obtained
from (R)-(+)-2b, using the previous procedure, as a colorless
oil; bp 92 °C/0.04 mmHg, [R]D +52.6° (c 2.5, CHCl3).
in the Experimental Section.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. Organic layers were
dried using anhydrous Na2SO4. Columns for chromatographic
separations were packed with Merck Si gel 60 (230-400 mesh
ASTM). Melting points were measured on a Melt-Temp II and
are uncorrected. Specific rotations [R]D were measured at the
sodium-D line using a Perkin-Elmer 241 polarimeter at 25
°C. The concentration, c, given after specific rotations is
indicated in g/100 mL. IR spectra were recorded on a Perkin-
Elmer 16F PC FT-IR spectrophotometer. UV spectra were
recorded on a Perkin-Elmer Lambda 2S spectrometer. 1H and
13C NMR measurements were performed on a Varian XL-
300GS spectrometer using CDCl3 solutions containing TMS
as internal standard. MS were obtained on a Hewlett-Packard
598A spectrometer at 20 eV. The 1H, 13C NMR, UV, IR, and
MS data for the b series are not described herein; they are
identical to those of the a series.
(S)-(+)-2,3-Dih yd r o-2-(2-h yd r oxyisop r op yl)-6-m eth oxy-
ben zofu r a n (5a ). A solution of (S)-(-)-4a (3.0 g, 14.4 mmol)
in 20 mL of dry Et2O was added dropwise to a solution of
methylmagnesium iodide, prepared from iodomethane (4.5 mL,
72.3 mmol) and magnesium turnings (1.4 g, 57.6 mmol) in dry
Et2O (20 mL), at room temperature under a nitrogen atmo-
sphere. After stirring for 12 h at room temperature, the
mixture was quenched with a saturated NH4Cl solution. The
reaction was extracted with Et2O (2 × 50 mL), the combined
organic layer was washed with H2O, dried, and concentrated.
The residue was purified by column chromatography eluting
with hexane-EtOAc (98:2) to afford (S)-(+)-5a (2.1 g, 70%) as
a colorless oil: bp 106 °C/0.04 mmHg; [R]D +33.5° (c 5.1,
CHCl3); UV (EtOH) λrnax (log ꢀ) 202 (1.58) nm; IR (dry film)
(S)-(-)-Meth ylben zylam m on iu m (S)-2,3-Dih ydr o-6-m eth -
oxyben zofu r a n -2-ca r boxyla te (3a ). To a stirred solution of
26 (10 g, 51.6 mmol) in Me2CO (40 mL) was added 6.7 mL (51.6
mmol) of (S)-(-)-R-MBA and further stirred for 1 min. The
white crystalline precipitate formed was filtered and washed
with Me2CO. Six recrystallizations from Me2CO gave 5 g of
the homogeneous salt (S)-(-)-3a as a white cotton-like mate-
rial, mp 164-166 °C; [R]D -72.6° (c 2.3, MeOH).
ν
max 3582 cm-1; 1H NMR (CDCl3, 300 MHz) δ 7.01 (1H, d, J )
8.8 Hz, H-4), 6.38 (1H, d, J ) 2.3 Hz, H-7), 6.38 (1H, dd, J )
8.8, 2.3 Hz, H-5), 4.60 (1H, t, J ) 9.0 Hz, H-2), 3.74 (3H, s,
OCH3), 3.06 (2H, d, J ) 9.0 Hz, CH2-3), 2.17 (1H, s, OH), 1.31
(R)-(+)-Met h ylb en zyla m m on iu m (R)-2,3-Dih yd r o-6-
m eth oxyben zofu r a n -2-ca r boxyla te (3b). The mother li-

Synthesis and Configuration of Methoxybenzofurans
J ournal of Natural Products, 1999, Vol. 62, No. 8 1087
(3H, s, CH3-2′), 1.19 (3H, s, CH3-3′); 1H NMR (C6D6, 300 MHz)
δ 6.87 (1H, d, J ) 8.1 Hz, H-4), 6.55 (1H, d, J ) 2.3 Hz, H-7),
6.43 (1H, dd, J ) 8.1, 2.3 Hz, H-5), 4.33 (1H, t, J ) 9.0 Hz,
H-2), 3.34 (3H, s, OCH3), 2.94 (1H, dd, J ) 15.1, 9.0 Hz, H-3â),
2.64 (1H, dd, J ) 15.1, 9.0 Hz, H-3R), 2.04 (1H, s, OH), 1.16
(3H, s, CH3-2′), 1.02 (3H, s, CH3-3′); 13C NMR (CDCl3, 74.5
MHz) δ 160.64 (s, C-6), 160.10 (s, C-7a), 124.68 (d, C-4), 118.90
(s, C-3a), 105.86 (d, C-5), 95.92 (d, C-7), 90.15 (d, C-2), 71.71
(s, C-1′), 55.35 (q, OCH3), 29.94 (t, C-3), 25.89 (q, C-2′), 23.90
(q, C-3′); EIMS m/ z 208 [M]+ (82), 149 (98), 148 (11), 59 (50).
(R)-(+)-2,3-Dih yd r o-2-(1-m et h ylet h en yl)-6-m et h oxy-
ben zofu r a n (1b). The olefin (R)-(+)-1b was prepared from
(R)-(-)-6b (2 g, 8.0 mmol) in the same way as described above,
giving (R)-(+)-1b (1.03 g, 68%) as a colorless oil: [R]D +5.4° (c
2.2, CHCl3).
(S)-(-)-2,3-Dih yd r o-2-ca r boxym eth yl-6-h yd r oxyben zo-
fu r a n (9). A mixture of 100 mg of prehydrogenated 5%
palladium on charcoal catalyst in EtOH and 1 g of the ester
(S)-(-)-8,11 [R]D -53° (c 2.5, CHCl3), dissolved in EtOH, was
shaken in a hydrogen atmosphere over 15 h. The catalyst was
filtered off and the EtOH evaporated under vacuum to give
(S)-(-)-9 (531 mg, 80%) as an amorphous solid: mp 125-127
°C; [R]D -44° (c 1.9, CHCl3); UV (EtOH) λmax (log ꢀ) 221 (4.42),
289 (4.16) nm; IR (KBr) νmax 3376, 1742, 1244, 1142 cm-1; 1H
NMR (CDCl3, 300 MHz) δ 6.97 (1H, d, J ) 8.0 Hz, H-4), 6.48
(1H, d, J ) 2.2 Hz, H-7), 6.37 (1H, dd, J ) 8.0, 2.2 Hz, H-5),
5.70 (1H, s, OH), 5.22 (1H, dd, J ) 10.5, 6.7 Hz, H-2), 3.81
(3H, s, COOCH3), 3.49 (1H, dd, J ) 15.4, 10.5 Hz, H-3â), 3.27
(1H, dd, J ) 15.4, 6.7 Hz, H-3R); 13C NMR (CDCl3, 74.5 MHz)
δ 172.12 (s, C-1′), 160.15 (s, C-6), 156.57 (s, C-7a), 124.83 (d,
C-4), 116.30 (s, C-3a), 108.24 (d, C-5), 98.18 (d, C-7), 79.76 (d,
C-2), 52.69 (q, COOCH3), 33.27 (t, C-3); EIMS m/ z 194 [M]+
(68), 162 (45), 134 (100), 107 (100), 77 (20).
(R)-(-)-2,3-Dih ydr o-2-(2-h ydr oxyisopr opyl)-6-m eth oxy-
ben zofu r a n (5b). Using the previous procedure, the Grignard
reaction with the ester (R)-(+)-4b (2.9 g) gave carbinol (R)-
(-)-5b (2.03 g, 70%) as a colorless oil: [R]D -33° (c 2.8; CHCl3).
(S)-(+)-2,3-Dih yd r o-2-(2-a cetoxyisop r op yl)-6-m eth oxy-
ben zofu r a n (6a ). A solution of (S)-(+)-5a (2 g, 9.6 mmol) in
5 mL of Ac2O was heated under reflux for 2 h. The solution
was poured over ice and extracted with Et2O. The organic layer
was washed with 2% aqueous NaOH (2 × 50 mL) and H2O,
dried, and evaporated. The residue was chromatographed,
eluting with hexane-EtOAc (99:1), to yield (S)-(+)-6a (1.92
g, 80%) as an amorphous solid: mp 88-90 °C; [R]D +42.8° (c
1.5, CHCl3); UV (EtOH) λmax (log ꢀ) 202 (1.71), 287 (0.81) nm;
1
IR (KBr) νmax 1732, 1198 cm-1; H NMR (CDCl3, 300 MHz) δ
7.01 (1H, d, J ) 8.8 Hz, H-4), 6.39 (1H, d, J ) 2.5 Hz, H-7),
6.39 (1H, dd, J ) 8.8, 2.5 Hz, H-5), 4.98 (1H, dd, J ) 9.6, 8.1
Hz, H-2), 3.75 (3H, s, OCH3), 3.13 (1H, dd, J ) 15.5, 9.6 Hz,
H-3â), 3.03 (1H, dd, J ) 15.5, 8.1 Hz, H-3R), 1.99 (3H, s,
COCH3), 1.55 (3H, s, CH3-2′), 1.49 (3H, s, CH3-3′); 13C NMR
(CDCl3, 74.5 MHz) δ 170.23 (s, COCH3), 160.94 (s, C-6), 160.29
(s, C-7a), 124.54 (d, C-4), 118.23 (s, C-3a), 105.94 (d, C-5), 95.89
(d, C-7), 87.48 (d, C-2), 82.56 (s, C-1′), 55.39 (q, OCH3), 30.07
(t, C-3), 22.27 (q, COCH3), 21.88 (q, C-2′), 20.88 (q, C-3′); EIMS
m/ z 250 [M]+ (10), 175 (100), 149 (7), 43 (8).
(S)-(-)-2,3-Dih yd r o-2-ca r boxym eth yl-6-m eth oxyben zo-
fu r a n (4a ). A mixture of K2CO3 (712 mg, 5.16,mmol), (S)-
(-)-9 (500 mg, 2.58 mmol) and iodomethane (0.16 mL, 2.58
mmol) in anhydrous Me2CO (30 mL) was refluxed for 3 h. The
reaction mixture was concentrated to a small volume under
vacuum, extracted with Et2O, washed with H2O, dried, and
evaporated. The residue was purified by column chromatog-
raphy eluting with hexane-EtOAc (98:2) to afford (S)-(-)-4a
(429 mg, 80%) as a colorless oil, [R]D -51.6° (c 2.0, CHCl3),
identical by IR, 1H NMR, and 13C NMR comparison to a sample
obtained as described above.
(R)-(-)-2,3-Dih yd r o-2-(2-a cetoxyisop r op yl)-6-m eth oxy-
ben zofu r a n (6b). Using the previous procedure, the acetyl-
ation of (R)-(-)-5b (2.5 g, 12 mmol) gave (R)-(-)-6b (2.34 g,
78%) as a white amorphous solid: mp 88-90 °C; [R]D -42.5°
(c 1.3, CHCl3).
Ack n ow led gm en t. Partial financial support from CoNa-
(S)-(-)-2,3-Dih ydr o-2-(1-m eth yleth en yl)-6-m eth oxyben -
zofu r a n (1a ) a n d 6-Meth oxy-2-isop r op ylben zofu r a n (7).
A sample of (S)-(+)-6a (1.5 g, 6 mmol) was heated in a muffle
furnace at 330 °C for 10 min. The evolution of HOAc began at
about 280 °C. The residue was allowed to cool to room
temperature, dissolved in Et2O, washed with 5% aqueous
NaHCO3 and H2O, dried, and evaporated. The residue was
purified by flash column chromatography eluting with petro-
leum ether-EtOAc (98:2) to give (S)-(-)-1a (800 mg, 70%, Rf
0.45, hexane-EtOAc 95:5) and 7 (100 mg, 8.2%, Rf 0.54.).
CyT (Me´xico) and Universidad Veracruzana is acknowledged.
Refer en ces a n d Notes
(1) (a) Formula Index, A-C15, Chem. Abstr. 1978, 88, 849F, left column,
ninth line from bottom. (b) Tenth Collective Index, Formula C11H12O5-
C13H16FN5, Chem. Abstr. 1977-1981, 86-95, 6195F, left column, 12th
line from bottom.
(2) (a) Formula Index, A-C15, Chem. Abstr. 1983, 98, 985F, left column,
33rd line from bottom. (b) Eleventh Collective Index, Formula C10H13
-
NOS-C12H15NO5V, Chem. Abstr. 1982-1986, 96-105, 6950F, central
column, 11th line from bottom.
Olefin (S)-(-)-1a : colorless oil; [R]D -5.8° (c 2.0, CHCl3);
UV (EtOH) λmax (log ꢀ) 202 (4.27), 248 (3.97), 255 (3.95), 290
(3) Bohlmann, F.; Mahanta, P. K.; Suwita, A.; Suwita, A.; Natu, A. A.;
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(8) Bowen, D. M.; DeGraw, J . I., J r.; Shah, V. R.; Bonner, W. A. J . Med.
Chem. 1963, 6, 315-319.
(9) Yamaguchi, S.; Miyata, A.; Ueno, M.; Hase, T.; Yamamoto, K.;
Kawase, Y. Bull. Chem. Soc. J pn. 1984, 57, 617-618.
(10) Asakawa, Y.; Hashimoto, T.; Takikawa, K.; Tori, M.; Ogawa, S.
Phytochemistry 1991, 30, 235-251.
(11) Harada, I.; Hirose, Y.; Nakazaki, M. Tetrahedron Lett. 1968, 5463-
5466.
1
(3.68) nm; IR (dry film) νmax 1654 cm-1; H NMR (CDCl3, 300
MHz) δ 7.01 (1H, dd, J ) 7.7, 1.2 Hz, H-4), 6.40 (1H, d, J )
2.2 Hz, H-7), 6.38 (1H, dd, J ) 7.7, 2.2 Hz, H-5), 5.17 (1H, t,
J ) 8.8 Hz, H-2), 5.07 (1H, m, H-2′a), 4.89 (1H, m, H-2′b), 3.75
(3H, s, OCH3), 3.26 (1H, dd, J ) 15.1, 8.8 Hz, H-3â), 2.95 (1H,
ddd, J ) 15.1, 8.8, 1.2 Hz, H-3R), 1.75 (3H, t, J ) 1.3 Hz, CH3-
3′); 13C NMR (CDCl3, 74.5 MHz) δ 161.00 (s, C-6), 160.39 (s,
C-7a), 144.09 (s, C-1′), 124.68 (d, C-4), 118.50 (s, C-3a), 111.87
(t, C-2′), 105.85 (d, C-5), 96.03 (d, C-7), 86.63 (d, C-2), 55.48
(q, OCH3), 34.10 (t, C-3), 17.19 (q, C-3′); EIMS m/ z 190 [M]+
(85), 175 (100), 160 (17), 41 (4).
Ben zofu r a n e 7: colorless oil; UV (EtOH) λmax (log ꢀ) 202
(4.27), 248 (3.97) 255 (3.95), 290 (3.68) nm; IR (dry film) νmax
1
2964, 1490, 1030, 820, 740 cm-1; H NMR (CDCl3, 300 MHz)
δ 7.31 (1H, d, J ) 8.5 Hz, H-4), 6.96 (1H, d, J ) 2.3 Hz, H-7),
6.80 (1H, dd, J ) 8.5, 2.3 Hz, H-5), 6.23 (1H, t, J ) 1.0 Hz,
H-3), 3.78 (3H, s, OCH3), 3.01 (1H, dh, J ) 6.9, 1.0 Hz, H-1′),
1.30 (6H, d, J ) 6.9 Hz, CH3-2′ and CH3-3′); 13C NMR (CDCl3,
74.5 MHz) δ 163.96 (s, C-2), 157.23 (s, C-6), 155.49 (s, C-7a),
122.18 (s, C-3a), 120.27 (d, C-4), 111.01 (d, C-5), 99.34 (d, C-3),
95.88 (d, C-7), 55.63 (q, OCH3), 28.20 (d, C-1′), 20.96 (q, C-2′
and C-3′); EIMS m/ z 190 [M]+ (48), 175 (100), 160 (7), 132
(8), 43 (28).
(12) Nakajima, M.; Oda, J .; Fukami, H. Agr. Biol. Chem. 1963, 27, 695-
699.
(13) PCMODEL Molecular Modeling program is available from Serena
Software, Box 3076, Bloomington, IN 47402-3076.
(14) Cerda-Garc´ıa-Rojas, C. M.; Zepeda, L. G.; J oseph-Nathan, P. Tetra-
hedron Comput. Methodol. 1990, 3, 113-118.
(15) J oseph-Nathan, P.; D´ıaz, E. Introduccio´n a la Resonancia Magne´tica
Nuclear; Limusa-Wiley: Me´xico, 1970; pp 40-46.
NP980521O