PAPER
Asymmetric Synthesis of Yangambin and Caruilignan A
403
crystallization from hexane–THF gave colorless crystals; mp 179–
(1S,2R,3R,4S)-2,3-Bis(hydroxymethyl)-1,4-bis(3,4,5-trimeth-
oxyphenyl)butane-1,4-diol (14)
180 °C; [a]D22 +37 (c = 1.0, CHCl3).
CaCl2 (1.26 g, 11.4 mmol) and NaBH4 (860 mg, 22.7 mmol) were
added to EtOH (20 mL). After stirring at r.t. for 15 min, 6 (770 mg,
1.62 mmol) in EtOH (5 mL) was added to the mixture. After stirring
at r.t. overnight, the reaction mixture was poured into diluted HCl
and extracted with CHCl3. The organic layer was washed with sat.
(NH4)2SO4 solution, dried with anhyd MgSO4 and concentrated in
vacuo. Recrystallization from EtOAc gave 14 (580 mg, 74%) as
colorless crystals; mp 204–205 °C; [a]D23 –31 (c = 1.0, MeOH).
IR (KBr): 2944, 2841, 1769, 1594, 1509, 1466, 1427, 1364, 1334,
1241, 1128, 1002 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.55 (s, 2 H, H-1, H-5), 3.81 (s, 6
H, OCH3), 3.86 (s, 12 H, OCH3), 5.87 (s, 2 H, H-4, H-8), 6.49 (s, 4
H, ArH).
13C NMR (75 MHz, CDCl3): d = 48.5, 56.3, 60.8, 81.5, 101.3, 133.6,
138.4, 153.9, 174.9.
IR (KBr): 3481, 2938, 1595, 1507, 1460, 1420, 1329, 1233, 1127,
999 cm–1.
Anal. Calcd for C24H26O10: C, 60.76; H, 5.52. Found: C, 60.91; H,
5.44.
1H NMR (300 MHz, CD3OD): d = 2.20–2.25 (m, 2 H, H-2, H-3),
3.72 (s, 18 H, OCH3), 3.72–3.88 (m, 4 H, CH2OH), 4.80 (d, J = 3.9
Hz, 2 H, H-1, H-4), 6.37 (s, 4 H, ArH).
13C NMR (75 MHz, CD3OD): d = 46.1, 56.2, 61.0, 61.8, 74.2, 103.9,
137.2, 141.3, 153.9.
Dimethyl (2R,3R)-Bis(3,4,5-trimethoxyphenylmethyl)butane-
dioate (7)
To a solution of 6 (non-recrystallized, 115 mg, 0.243 mmol) in
EtOH–AcOH (8 mL, 1:1) was added 10% Pd/C (230 mg) and the
mixture was stirred at r.t. for 2 d under H2 atmosphere. The mixture
was filtered through Celite® and concentrated in vacuo. The residue
was dissolved in MeOH (10 mL) and treated with a solution of
CH2N2 in Et2O at 0 °C. After addition of few drops of AcOH to de-
stroy the unreacted CH2N2, the reaction mixture was concentrated
in vacuo. The residue was chromatographed over silica gel. Elution
with hexane–EtOAc (2:1–1:2) gave crude 7 (98.0 mg, 80%, > 95%
ee). Recrystallization from hexane–EtOAc gave pure 7 (> 99% ee)
as colorless crystals. HPLC [column: Daicel Chiralcel OD (0.46 cm
× 25 cm), eluent: hexane–i-PrOH (2.5:1), flow rate: 0.9 mL/min, de-
tection: UV (254 nm)]: tR = 15.7 min [(R,R)-isomer]; tR = 18.8 min
[(S,S)-isomer]; mp 100–102 °C; [a]D21 –39 (c = 1.0, CHCl3).
Anal. Calcd for C24H34O10: C, 59.74; H, 7.10. Found: C, 59.34; H,
7.03.
(1S,3aR,4S,6aR)-1,3a,4,6a-Tetrahydro-1,4-bis(3,4,5-trimeth-
oxyphenyl)-3H,6H-furo[3,4-c]furan (1, Yangambin)
To a solution of 14 (100 mg, 0.207 mmol) in pyridine (1.8 mL) were
added DMAP (4.3 mg) and MsCl (48 mL, 0.622 mmol) at 0 °C. Af-
ter stirring at 0 °C for 6 h, the mixture was warmed to r.t. and stirring
was continued for 2 d. The reaction mixture was poured into H2O
and extracted with EtOAc. The organic layer was dried with anhyd
MgSO4 and concentrated in vacuo. The residue was chromato-
graphed over silica gel. Elution with hexane–EtOAc (1:1) gave 1
(88.9 mg, 96%). Recrystallization from EtOAc gave colorless crys-
tals; mp 119–120 °C; [a]D23 +44 (c = 1.0, CHCl3) {Lit.17 [a]D29 +46
(c = 0.4, CHCl3)}.
IR (KBr): 2943, 2834, 1734, 1589, 1509, 1456, 1437, 1243, 1167,
1002 cm–1.
1H NMR (300 MHz, CDCl3): d = 2.90–3.30 (m, 6 H, H-2, H-3,
CH2Ar), 3.66 (s, 6 H, COOCH3), 3.78 (s, 12 H, OCH3), 3.80 (s, 6 H,
OCH3), 6.29 (s, 4 H, ArH).
13C NMR (75 MHz, CDCl3): d = 35.9, 47.5, 51.8, 60.0, 60.8, 105.8,
134.2, 136.5, 153.1, 173.6.
IR (KBr): 2952, 2824, 1588, 1510, 1464, 1422, 1329, 1238, 1131,
998 cm–1.
1H NMR (300 MHz, CDCl3): d = 3.09–3.13 (m, 2 H, H-3a, H-6a),
3.83 (s, 6 H, OCH3), 3.87 (s, 12 H, OCH3), 3.93 (dd, J = 3.6, 9.3 Hz,
2 H, Ha-3, Ha-6), 4.31 (dd, J = 6.6, 9.3 Hz, 2 H, Hb-3, Hb-6), 4.75 (d,
J = 3.3 Hz, 2 H, H-1, H-4), 6.57 (s, 4 H, ArH).
Anal. Calcd for C26H34O10: C, 61.65; H, 6.77. Found: C, 61.67; H,
6.71.
13C NMR (75 MHz, CDCl3): d = 54.3, 56.1, 60.8, 71.9, 85.9, 102.7,
(2R,3R)-Bis(3,4,5-trimethoxyphenylmethyl)butane-1,4-diol (8)
To a solution of 7 (72.3 mg, 0.143 mmol) in THF (5 mL) was added
LiAlH4 (20.0 mg, 0.527 mmol) at 0 °C. The reaction mixture was
stirred at r.t. for 2 h, and then cooled to 0 °C. H2O and 3 N HCl were
added to the mixture and the reaction mixture was extracted with
CHCl3. The organic layer was dried with anhyd MgSO4 and concen-
trated in vacuo. The residue was chromatographed over silica gel.
Elution with EtOAc gave 8 (58.9 mg, 92%). Recrystallization from
hexane–EtOAc gave colorless crystals; mp 146–149 °C; [a]D21 –30
(c = 1.0, CHCl3), {Lit.16 (S,S)-8: [a]D23 +23.6 (c = 0.11, CHCl3)}.
136.7, 137.4, 153.4.
Anal. Calcd for C24H30O8: C, 64.56; H, 6.77. Found: C, 64.75; H,
6.75.
(1R,3aR,4S,6aR)-1,3a,4,6a-Tetrahydro-1,4-bis(3,4,5-trimeth-
oxyphenyl)-1-methoxy-3H,6H-furo[3,4-c]furan (2, Caruilignan
A)
To a solution of 1 (20 mg, 0.045 mmol) in CH2Cl2 (2 mL) were add-
ed DDQ (10.2 mg, 0.045 mmol) and MeOH (0.1 mL) at 0 °C. After
stirring at 0 °C for 3 h, the remaining DDQ was destroyed by the ad-
dition of NaBH4 (ca. 10 mg). The reaction mixture was poured into
H2O and extracted with Et2O. The organic layer was dried with an-
hyd MgSO4 and concentrated in vacuo. The residue was purified by
preparative TLC [hexane–EtOAc (1:1)] to give 2 (4.0 mg, 19%) as
an amorphous solid with recovery of 1 (16.2 mg, 81%); [a]D27 +86
(c = 0.93, CHCl3) {Lit.9 [a]D24 +62 (c = 0.83, CHCl3)}.
IR (KBr): 3503, 2933, 2835, 1593, 1508, 1462, 1422, 1238, 1133,
1039, 1007 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.87–1.93 (m, 2 H, H-2, H-3), 2.68
(dd, J = 6.3, 13.8 Hz, 2 H, CHaAr), 2.78 (dd, J = 7.8, 13.8 Hz, 2 H,
CHbAr), 3.56 (dd, J = 3.9, 11.4 Hz, 2 H, Ha-1, Ha-4), 3.80 (s, 12 H,
OCH3), 3.81 (s, 6 H, OCH3), 3.81–3.86 (m, 2 H, Hb-1, Hb-4), 6.35
(s, 4 H, ArH).
13C NMR (75 MHz, CDCl3): d = 36.6, 43.7, 56.1, 60.6, 60.8, 105.9,
136.2, 136.3, 153.1.
IR (KBr): 2939, 1593, 1506, 1460, 1415, 1342, 1234, 1126, 1005
cm–1.
1H NMR (300 MHz, CDCl3): d = 2.99 (s, 3 H, OCH3-1), 3.04 (m, 1
H, H-3a), 3.10 (t, J = 8.7 Hz, 1 H, Ha-6), 3.31 (q, J = 8.7 Hz, 1 H,
H-6a), 3.83 (s, 3 H, ArOCH3), 3.86 (m, 1 H, Hb-6), 3.87 (s, 9 H,
ArOCH3), 3.89 (s, 6 H, ArOCH3), 4.06–4.16 (m, 2 H, H-3), 4.48 (d,
J = 6.6 Hz, 1 H, H-4), 6.57 (s, 2 H, ArH), 6.72 (s, 2 H, ArH).
Anal. Calcd for C24H34O8: C, 63.98; H, 7.61. Found: C, 63.69; H,
7.58.
Synthesis 2006, No. 3, 400–404 © Thieme Stuttgart · New York