6
HWANG ET AL.
CH2Cl2 (100 mL). The resulting organic extracts were
combined, washed with H2O (50 mL), and dried (MgSO4).
After evaporation of the solvent in vacuo, a mixture of the
lactone alcohol O,O0-dibenzyl-7α,7'α and 7β,7'β–
dihydroxy-50-methoxymatairesinols (31a/b) (550 mg,
0.916 mmol, 90% yield) was obtained as white foam. This
product was used without further purification. To a stirred
suspension of LiAlH4 (197.2 mg, 5.2 mmol) in dry THF
(5 mL) under Ar, the lactone alcohol 31a/b (~380 mg,
0.633 mmol) in THF (20 mL) was added dropwise. The
reaction mixture was stirred at room temperature for
1.5 hours and then cooled to 0ꢀC. Excess LiAlH4 was des-
troyed with EtOAc (3 mL), with H2O (20 mL) next added.
The resulting mixture was then extracted with EtOAc
(30 mL × 3). The combined EtOAc solubles were dried
(MgSO4), evaporated in vacuo, with the residue so
obtained subjected to silica gel CC (eluent, CHCl3:MeOH,
20:1) to afford a mixture of O,O0-dibenzyl-7α,7'α and
7β,7'β-dihydroxy-50-methoxysecoisolariciresinols (32a/b,
320 mg, 0.53 mmol, 83.7% yield). To a stirred solution of
32a/b (280 mg, 0.464 mmol) in CH2Cl2 (20 mL) under Ar
at 0ꢀC, Me3SiBr (132 μL, 1.0 mmol) was added dropwise.
The reaction mixture was allowed to stir for 10 minutes at
0ꢀC, then quenched by adding saturated NaHCO3
(20 mL). The organic layer was separated, and the H2O
phase extracted with CH2Cl2 (50 mL × 3). The combined
CH2Cl2 solubles were washed successively with H2O
(50 mL) and brine (50 mL), then dried (MgSO4). After
removal of the solvent in vacuo, the resulting residue was
subjected to silica gel CC (eluent, hexanes:EtOAc, 3:1, v/v)
to afford O,O0-dibenzylmedioresinols (33a/b) (100 mg,
0.176 mmol, 34% yield) as a syrup. To a solution of 33a/b
(390 mg, 0.07 mmol) in EtOAc (10 mL) was added 10%
Pd/C (100 mg), with the resulting suspension stirred at
room temperature under H2 for 2 hours. The reaction mix-
ture was diluted with EtOAc (10 mL) and filtered through
Celite (1 g). The resulting filtrate was evaporated to dry-
ness in vacuo, with the residue applied to a silica gel col-
umn (eluent, hexanes:EtOAc, 2:1, v/v) to yield ( )-
medioresinols (8a/b) (150 mg, 0.387 mmol, 56% yield).
The mass, 1H and 13C NMR spectra for 8a/b were in close
agreement with reported data.28,40 HRMS (ESI, m/z):
[M − H]− calcd for C21H23O7, 387.1444; found, 387.1446,
[M + HCOO]− calcd for C22H25O9, 433.1499; found,
433.1508.
( )-5-Methoxylariciresinols (13a/b): 1H NMR
(500 MHz, CDCl3, δ); 2.41 (m, 1H, H-8), 2.54 (dd, 1H,
J = 13.5, 10.5 Hz, Hβ-70), 2.72 (m, 1H, H-80), 2.9 (dd, 1H,
J = 13.1, 5.3 Hz, Hα-70), 3.76 (dd, 1H, J = 8.5, 6.5 Hz, Hβ-
90), 3.80 (dd, 1H, J = 7, 11 Hz, Hβ-9), 3.86 (s, 3H, OMe),
3.88 (6H, 2 × OMe), 3.92 (dd, 1H, J = 7, 11.0 Hz, Hα-9),
4.06 (dd, 1H, J = 6.5, 8.5 Hz, Hα-90), 4.80 (d, 1H, J = 6 Hz,
H-7), 5.5 (s, Ar-OH), 5.56 (s, 1H, Ar-OH), 6.56 (s, 2H, H-
2, H-6), 6.68 (d, 2H, J = 6 Hz, H-20, H-60), 6.83 (d, 1H,
J = 8.5 Hz, H-50); 13C NMR (500 MHz, CDCl3, δ): 33.27
(C70), 42.3 (C80), 52.55 (C8), 55.88 (OMe), 56.3 (2 × OMe),
60.9 (C9), 72.9 (C90), 83.0 (C7), 102.39 (C2, C6), 111.1
(C20), 114.39 (C50), 121.1 (C60), 132.19 (C10), 133.9 (C1),
133.98 (C4), 143.9 (C40), 146.5 (C30), 147.0 (C3, C5).
HMBC correlation (500 MHz, CD3OD, δ) proton and cor-
related carbons: 2.41 (C70, C80, C8, C9, C90, C7, C4), 2.54
(C80, C8, C90, C20, C60, C10), 2.72 (C8, C9, C90, C7, C10),
2.9 (C8, C80 C90, C20, C60, C10), 3.76 and 4.06 (C70, C80,
C8, C30-OMe, C3,5-OMe, C90, C7), 3.80 and 3.92 (C80, C8,
C7), 3.86 (C30-OMe, C2, C6, C30), 3.88 (C3,5-OMe, C2,
C6, C3, C5), 4.80 (C8, C80, C90, C90, C1, C2, C6), 6.56 (C7,
C2, C6, C1, C60, C3, C5), 6.68 (C70, C20, C50, C60, C10, C30,
C40), 6.83 (C20, C60, C10, C30). HSQC correlation
(500 MHz, CD3OD, δ) proton and correlated carbons:
2.41 (C8), 2.54 (C8, C70), 2.72 (C80), 2.9 (C70), 3.76 and
4.06 (C90), 3.80 and 3.92 (C9), 3.86 (C30-OMe), 3.88
(C3,5-OMe), 4.8 (C7), 6.56 (C2, C6), 6.68 (C60, C50, C20),
6.83 (C50, C60). LC APCI (m/z) 389.1 [M − H]−
(tR = 24.18 min). HRMS (ESI, m/z): [M − H]− calcd for
C21H25O7, 389.1600; found, 389.1596, [M + HCOO]−
calcd for C22H27O9, 435.1655; found, 435.1654.
1
( )-50-Methoxysecoisolariciresinols (19a/b): H NMR
(600 MHz, CDCl3, δ): 1.86 (m, 2H, H-8, H-80), 2.17 (s,
1H, OH), 2.18 (s, 1H, OH), 2.65 (dd, 1H, J = 7.8,
16.8 Hz, Hβ-70), 2.67 (dd, 1H, J = 7.8, 16.8 Hz, Hβ-7),
2.7 (m, 1H, Hα-7), 2.75 (m, 1H, Hα-70), 3.57 (d, 2H,
J = 4.8 Hz, Hβ-9, Hβ-90), 3.59 (d, 2H, J = 5.4 Hz, Hα-9,
Hα-90), 3.82 (s, 3H, OMe), 3.85 (s, 6H, 2 × OMe), 5.38
(s, 1H, Ar-OH), 5.49 (s, 1H, Ar-OH), 6.33 (s, 2H, H-20,
H-60), 6.58 (d, 1H, J = 1.8 Hz, H-2), 6.63 (dd, 1H,
J = 1.8, 9.6 Hz, H-6), 6.8 (d, 1H, J = 9.6 Hz, H-5); 13C
NMR (600 MHz, CDCl3, δ): 36.0 (C7), 36.5 (C70), 43.8
(C8), 43.84 (C80), 55.8 (OMe), 56.2 (2 × OMe), 61.0
(C9), 61.2 (C90), 104.8 (C20, C60), 111.6 (C2), 114.0 (C5),
121.8 (C6), 131.8 (C1), 132.2 (C10), 132.5 (C40), 143.8
(C4), 146.5 (C3), 147.0 (C30, C50). HMBC correlation
(500 MHz, CD3OD, δ) (proton and correlated carbons):
2.65 and 2.67 (C8, C9, C20, C60, C2, C6, C1), 3.57, 3.59
and 3.82 (C80, C7, C70), 3.82 and 3.85 (C3), 6.33 (C70,
C20, C60, C1, C10, C30, C50), 6.58 (C7, C6, C4, C3), 6.63
(C7, C2, C4), 6.8 (C40, C4, C3). HSQC correlation
(600 MHz, CD3OD, δ)-(proton and correlated carbons):
1.86 (C8, C80), 3.57 and 3.59 (C9, C90), 3.82 and 3.85
( )-5-Methoxylariciresinols (13a/b) and ( )-50-
methoxysecoisolariciresinols (19a/b) were synthesized
and purified (as described above for 11a/b and 17a/b) via
Pd/C-hydrogenation (5 mg) of 8a/b (15 mg, 0.038 mmol)
in MeOH (2 mL) at room temperature under H2 for
6 hours. The residue so obtained was purified as above to
yield 13a/b (10 mg, 0.025 mmol, 66% yield)41 and 19a/b
(2 mg, 0.005 mmol, 13% yield).