Synthesis of Novel p-Anisylpropanoid Metabolites
J ournal of Natural Products, 1998, Vol. 61, No. 9 1113
anal. C 55.71%; H 5.09%, calcd for C10H11ClO3, C
55.95%, H 5.17%.
EtOAc)] to give 4.02 g (57%) of 13 as a light yellow oil:
1H NMR δ 7.94 (1H, d, J ) 2.1 Hz, C-2′), 7.82 (1H, J )
8.6, 2.1 Hz, H-6′), 6.94 (1H, J ) 8.6 Hz, C-5′), 6.14 (1H,
dd, J ) 19.4, 14.6 Hz, Si-CHdCH2), 5.95 (1H, dd, J )
14.6, 4.8 Hz, Si-CHdCHcis), 5.69 (1H, dd, J ) 19.4, 4.8
Hz, Si-CHdCHtrans), 3.93 (3H, s, COCH3), 2.88-2.80
(2H, m, H2-2), 0.97-0.89 (2H, m, H2-3), 0.09 (6H, s, Si-
(CH3)2); 13C NMR δ 198.7 (s, C-1), 158.5 (s, C-4′), 138.1
(d, SiCHdC), 132.4 (t, SiCdCH2), 130.4 (d, C-2′),* 130.3
(s, C-1′), 128.4 (d, C-6′),* 122.7 (s, C-3′), 111.2 (d, C-5′),
56.3 (q, COCH3), 32.7 (t, C-2), 9.6 (t, C-3), -3.5 (q, Si-
(CH3)2); EIMS m/z 284 [M + 2]+ (1.7), 282 [M]+ (4.9),
281 (13), 267 (93), 255 (84), 169 (97), 146 (34), 85 (100),
75 (29), 59 (77); HREIMS m/z [M]+ 282.0841 (calcd for
C14H19ClO2Si, 282.0843); anal. C 59.39%; H 7.08%, calcd
for C14H19ClO2Si, C 59.47%, H 6.77%.
(()-1-(3′,5′-Dich lor o-4′-m eth oxyph en yl)-2-h ydr oxy-
1-p r op a n on e (11). The same procedure applied on 232
mg (1.0 mmol) of 9 afforded 175 mg (71%) of 11 as a
colorless oil that solidified on standing: mp 48-49 °C;
1H NMR δ 7.84 (2H, s, H-2′, H-6′), 5.04 (1H, q, J ) 7.0
Hz, H-2), 3.95 (3H, s, COCH3), 3.61 (1H, br, OH), 1.42
(3H, d, J ) 7.0 Hz, H3-3); 13C NMR δ 199.5 (s, C-1), 156.8
(s, C-4′), 130.3 (s, C-1′),* 130.2 (s, C-3′, C-5′),* 129.4 (d,
C-2′, C-6′), 69.4 (d, C-2), 61.0 (q, COCH3), 22.1 (q, C-3);
EIMS m/z 250 [M + 2]+ (0.7), 248 [M]+ (1.2), 207 (29),
205 (96), 203 (100), 162 (14), 142 (31), 111 (19), 97 (21),
45 (29); HREIMS m/z [M]+ 248.0001 (calcd for C10H10
-
Cl2O3, 248.0007); anal. C 48.35%; H 4.06%, calcd for
C10H10Cl2O3, C 48.21%, H 4.05%.
1-(3′-Ch lor o-4′-m eth oxyp h en yl)-3-h yd r oxy-1-p r o-
p a n on e (3). To a solution of 3.63 g (12.9 mmol) of 13
in a mixture of 25 mL of CH2Cl2 and 16 mL of
CF3COOH was added 2.0 g (25.3 mmol) of KHF2. The
reaction mixture was refluxed for 2.5 h, allowed to come
to 25 °C, and then poured into ice-water. After
extraction with petroleum ether (bp 40-60 °C), the
combined organic layers were washed with saturated
aqueous NaHCO3, dried, and evaporated to give 3.1 g
of the crude silyl fluoride as a yellow oil: HREIMS m/z
[M - 15]+ 259.0348 (calcd for C11H13ClFO2Si, 259.0357).
To a stirred solution of this crude silyl fluoride in 50
mL of a 1:1 mixture of MeOH and THF were added
successively 1.27 g (21.9 mmol) of KF, 1.0 g (11.9 mmol)
of NaHCO3, and 2.86 mL (32.7 mmol) of 35% H2O2. After
being stirred at 25 °C overnight, the reaction mixture
was cooled to 0 °C and quenched with diluted aqueous
NaHSO3. After filtration, the aqueous mixture was
extracted with ether, and the combined organic layers
were washed with saturated aqueous NaHCO3, dried,
and evaporated. The remaining residue was crystal-
lized from a 9:1 mixture of petroleum ether (bp 40-60
°C) and EtOAc, respectively, to give 1.93 g (70%) of 3
(()-er yth r o-1-(3′-Ch lor o-4′-m et h oxyp h en yl)-1,2-
p r op a n ed iol [(()-Tr a m etol] (1). To a stirred solution
of 54 mg (0.25 mmol) of 10 in 4 mL of ether was added
dropwise 1.0 mL (0.14 mmol) of Zn(BH4)2 (0.14 M in
ether) at 0 °C. After being stirred at 0 °C for 30 min,
the reaction mixture was quenched with a few drops of
water. Stirring was continued for an additional 30 min,
and then anhydrous MgSO4 was added. After filtration
and evaporation of the solvent under reduced pressure,
the remaining residue was flash chromatographed [1:1
petroleum ether (bp 40-60 °C)/EtOAc)] to give 52 mg
(95%) of 1 as a white solid: mp 117-118 °C (lit.11 (-)-1
mp 74 °C); 1H NMR spectrum was as previously
reported for (-)-1;11 13C NMR δ 154.5 (s, C-4′), 133.4 (s,
C-1′), 128.5 (d, C-2′),* 126.1 (d, C-6′),* 122.3 (s, C-3′),
111.7 (d, C-5′), 76.4 (d, C-1), 71.1 (d, C-2), 56.2 (q,
COCH3), 17.2 (q, C-3); EIMS m/z 218 [M + 2]+ (0.7),
216 [M]+ (2), 173 (34), 171 (100), 143 (16), 128 (9), 108
(32), 77 (11), 65 (9), 45 (7); HREIMS m/z [M]+ 216.0552
(calcd for C10H13ClO3, 216.0553).
(()-er yth r o-1-(3′,5′-Dich lor o-4′-m eth oxyp h en yl)-
1,2-p r op a n ed iol (2). The same procedure applied on
54 mg (0.22 mmol) of 11 afforded 53 mg (97%) of 2 as a
1
as white needles: mp 77-78 °C; H NMR δ 7.98 (1H,
1
white solid: mp 100-102 °C; H NMR δ 7.25 (2H, s,
d, J ) 2.2 Hz, H-2′), 7.86 (1H, dd, J ) 8.6, 2.2 Hz, H-6′),
6.96 (1H, d, J ) 8.6 Hz, H-5′), 3.99 (2H, t, J ) 5.2 Hz,
H2-2), 3.96 (3H, s, COCH3), 3.14 (2H, t, J ) 5.2 Hz, H2-
3), 2.63 (1H, br, OH); 13C NMR δ 198.1 (s, C-1), 159.1
(s, C-4′), 130.4 (d, C-2′),* 130.2 (s, C-1′), 128.6 (d, C-6′),*
123.0 (s, C-3′), 111.3 (d, C-5′), 58.1 (t, C-3), 56.4 (q,
COCH3), 40.0 (t, C-2); EIMS m/z 216 [M + 2]+ (2.4), 214
[M]+ (7.7), 196 (12), 184 (5), 169 (100), 141 (7), 126 (12),
111 (8), 77 (17), 63 (14); HREIMS m/z [M]+ 214.0399
(calcd for C10H11ClO3, 214.0397); anal. C 55.77%; H
5.17%, calcd for C10H11ClO3, C 55.95%, H 5.17%.
H-2′, H-6′), 4.56 (1H, d, J ) 4.0 Hz, H-1), 3.94 (1H, dq,
J ) 6.3, 4.0 Hz, H-2), 3.85 (3H, s, COCH3), 2.78 (2H,
br, 2 × OH), 1.02 (3H, d, J ) 6.3 Hz, H3-3); 13C NMR δ
151.3 (s, C-4′), 138.0 (s, C-1′), 129.1 (s, C-3′, C-5′), 127.0
(d, C-2′, C-6′), 75.9 (d, C-1), 70.9 (d, C-2), 60.7 (q,
COCH3), 17.1 (q, C-3); EIMS m/z 252 [M + 2]+ (0.4),
250 [M]+ (0.7), 209 (11), 207 (54), 205 (87), 191 (37), 177
(18), 142 (100), 99 (36), 45 (40); HREIMS m/z [M]+
250.0158 (calcd for C10H12Cl2O3, 250.0164); anal. C
47.55%; H 4.72%, calcd for C10H12Cl2O3, C 47.83%, H
4.82%.
Ack n ow led gm en t. This project was financially sup-
ported by the Technology Foundation, Utrecht, The
Netherlands, under project no. WLM33.3127, entitled
“Fungal Chlorinated Aromatic Metabolites: Natural
Priority Pollutants and Dioxin Precursors in the Envi-
ronment”. The authors are grateful to Dr. O. Vajna de
Pava from the Dipartimento di Chimica del Politecnico
di Milano, Italy, for the gift of a sample of (-)-trametol
(1).
[3-(3′-Ch lor o-4′-m eth oxyph en yl)-3-oxo]pr opyldim -
eth ylvin ylsila n e (13). A mixture of 1.21 g (50.0 mmol)
of Mg powder, 0.2 g (0.8 mmol) of I2, and 23.5 g (200
mmol) of chlorodimethylvinylsilane in 50 mL of N-
methylpyrrolidinone was stirred at 25 °C for 5 min, after
which time 5.0 g (25.0 mmol) of methyl 3-chloro-4-
methoxybenzoate (12) was added in small portions. The
reaction mixture was stirred at 25 °C overnight and
then quenched with diluted aqueous NH4Cl. After
extraction with EtOAc, the combined organic layers
were washed with saturated aqueous NaHCO3, dried,
and evaporated. The remaining residue was flash
chromatographed [30:1 petroleum ether (bp 40-60 °C)/
Refer en ces a n d Notes
(1) Gribble, G. W. Fortschr. Chem. Org. Naturst. 1996, 68, 1-498.
(2) Field, J . A.; Verhagen, F. J . M.; de J ong, E. Trends Biotechnol.
1995, 13, 451-456.