PAPER
Total Synthesis of Genistein and Orobol 6,8-Di-C-b-D-glucopyranosides
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1
were washed with aq 0.5 M HCl (7 mL) and brine (10 mL), and
dried (Na2SO4). After evaporation of the solvent in vacuo, the resi-
due was purified by silica gel column chromatography (1:1 n-hex-
ane–EtOAc) to afford 9 (58.2 mg, 29% from 5). To a solution of 9
(58.2 mg) in anhyd MeOH (1 mL) was added 28% NaOMe in
MeOH (0.05 mL, ca. 50 mg), followed by stirring at r.t. for 1 h. Af-
ter monitoring by TLC, Dowex® 50WX8-200 (H+) resin was added
to the mixture until the pH was neutral. The mixture was filtered,
and then washed with MeOH (5 mL). The filtrate was evaporated in
vacuo to afford 2 (27.5 mg, 25% from 5) as a yellow solid.
Mp 228–230 °C (Lit.3 mp 225 °C, Lit.4 mp 222–224 °C, Lit.2 mp
225–227 °C); [a]D21 +72 (c 0.54, MeOH).
IR (KBr): 3346, 2925, 2893, 1709, 1647, 1585, 1516 1458 cm–1.
1H NMR (500 MHz, DMSO-d6 + D2O at 90 °C): d = 3.30–3.34 (m,
6 H, H-3, 3¢, 4, 4¢, 5, 5¢), 3.37 (dd, J = 11.3, 4.1 Hz, 2 H, H-6a, 6¢a),
3.70 (dd, J = 11.3, 1.9 Hz, 2 H, H-6b, 6¢b), 3.80 and 3.81 (2 t, J = 8.3
Hz, each 1 H, H-2, 2¢), 4.80 and 4.84 (2 d, J = 9.8 Hz, each 1 H, H-
1, 1¢), 6.83 (dd, J = 9.0, 1.9 Hz, 2 H, H-3¢, 5¢), 7.37 (dd, J = 2.1, 9.0
Hz, 2 H, H-2¢, 6¢), 8.27 (s, 1 H, H-2), 9.29 (br s, 2 H, 2 × OH), 9.60
(br s, 1 H, OH), 13.64 (s, 1 H, OH).
2
Mp 234–237 °C (dec.) (Lit.3 183–186 °C, Lit.4 mp 240-241 °C);
MS (FAB+): m/z = 595 (M + H)+.
[a]D21 +56 (c 0.275, MeOH).
Anal. Calcd for C27H30O15·1.5H2O: C, 52.17; H, 5.35. Found: C,
52.34; H, 5.31.
IR (KBr): 3367, 2925, 1716, 1701, 1635, 1522, 1458 cm–1.
1H NMR (500 MHz, DMSO-d6 + D2O at 100 °C): d = 3.28–3.35 (m,
6 H, H-3, 3¢, 4, 4¢, 5, 5¢), 3.59 (dd, J = 11.8, 4.5 Hz, 2 H, H-6a, 6¢a),
3.72 (dd, J = 11.6, 5.8 Hz, 2 H, H-6b, 6¢b), 3.82 and 3.84 (2 m, each
1 H, H-2, 2¢), 4.81 and 4.84 (2 d, J = 9.6 Hz, each 1 H, H-1, 1¢), 6.80
(d, J = 8.1 Hz, 1 H, H-5¢), 6.83 (dd, J = 2.0, 8.2 Hz, 1 H, H-6¢), 7.03
(d, J = 2.1 Hz, 1 H, H-2¢), 8.23 (s, 1 H, H-2), 9.05 (br s, 2 H, 2 ×
OH ), 9.29 (br s, 1 H, OH), 13.79 (s, 1 H, OH).
6,8-Di-C-b-D-glucopyranosyl-2,4,4¢-trihydroxyisoflavone
Undecaacetate (8)
Mp 164–166 °C (Lit.3 160 °C); [a]D21 –33 (c 0.505, CHCl3).
IR (KBr): 2943, 1759, 1655, 1604, 1508 cm–1.
1H NMR (500 MHz, CDCl3): d (isoflavone moiety) = 2.32, 2.46,
2.53 (3 s, each 3 H, 3 × ArOCOCH3), 7.16 and 7.50 (2 d, J = 8.5 Hz,
each 2 H, H-3¢, 5¢ and H-2¢, 6¢), 8.03 (s, 1 H, H-2); d (glucose moi-
ety) = 1.751, 1.918, 2.024, 2.045, 2.048, 2.051, 2.067, 2.078 (8 s,
each 3 H, 8 × OCOCH3), 3.72 and 3.80 (2 m, each 1 H, H-5¢, 5),
3.95 and 4.15 (2 dd, J = 1.2, 12.6 Hz and 2.2, 12.4 Hz, each 1 H, H-
6a, 6¢a), 4.21 and 4.45 (2 dd, J = 5.4, 12.2 Hz and 4.9, 12.9 Hz, each
1 H, H-6¢b, 6b), 4.54 and 4.81 (2 d, J = 10.2 and 9.0 Hz, each 1 H,
H-1¢, 1), 5.15 and 5.24 (2 t, J = 9.8 Hz, each 1 H, H-4¢, 4), 5.30 and
5.37 (2 dd, J = 9.3, 9.5 Hz, each 1 H, H-3¢, 3), 5.69 and 5.96 (2 br t
and t, J = 9.6 Hz, each 1 H, H-2¢, 2).
MS (FAB+): m/z = 611 (M + H)+.
Anal. Calcd for C27H30O16·2.5H2O: C, 49.47; H, 5.38. Found: C,
49.62; H, 5.35.
6,8-Di-C-b-D-glucopyranosyl-2,3¢,4,4¢-tetrahydroxyisoflavone
Dodecaacetate (9)
Mp 157–159 °C (Lit.3 mp 150 °C); [a]D21 –31 (c 0.53, CHCl3,).
IR (KBr): 2943, 1755, 1655, 1604, 1506 cm–1.
1H NMR (500 MHz, CDCl3): d (isoflavone moiety) = 2.312, 2.465,
2.529 (2 s, each 3 H, 3 × ArOCOCH3), 7.26 and 7.38 (2 d, J = 8.5
Hz, each 2 H, H-3¢, 5¢ and H-2¢, 6¢), 8.06 (s, 1 H, H-2); d (glucose
moiety) = 1.748, 1.914, 2.024, 2.050, 2.052, 2.068, 2.073, 2.078 (8
s, each 3 H, 8 × OCOCH3), 3.72 (ddd, J = 2.1, 5.3, 9.8 Hz, 1 H, H-
5¢), 3.95 (m, 1 H, H-6a), 4.15 (dd, J = 2.1, 12.3 Hz, 1 H, H-6¢a), 4.21
(dd, J = 5.3, 12.3 Hz, 1 H, H-6¢b), 4.46 (dd, J = 4.1, 12.3 Hz, 1 H,
H-6b), 4.53 (d, J = 10.0 Hz, 1 H, H-1¢), 4.80 (d, J = 8.5 Hz, 1 H, H-
1), 5.15 and 5.24 (2 t, J = 9.8 Hz, each 1 H, H-4¢, 4), 5.30 and 5.37
(2 t, J = 9.4 Hz, each 1 H, H-3¢, 3), 5.69 (br t, 1 H, H-2¢), 5.95 (dd,
J = 9.4, 10.0 Hz, 1 H, H-2).
MS (FAB+): m/z = 1057 (M + H)+.
Anal. Calcd for C49H52O26: C, 55.68; H, 4.96. Found: C, 55.42; H,
4.90.
6,8-Di-C-b-D-glucopyranosyl-2,3¢,4,4¢-tetrahydroxyisoflavone
(2)
To a solution of DIB (177.8 mg, 0.552 mmol) and p-TsOH·H2O
(143.1 mg, 0.752 mmol) in anhyd MeOH (0.5 mL) was added drop-
wise a solution of 5 (194.1 mg, 0.183 mmol) in anhyd MeOH (0.9
mL) and the mixture stirred at r.t. for 1 d. To the stirred reaction
mixture was added aq 10% Na2S2O3 (40 mL). The resulting mixture
was passed through an MCI gel® CHP20P column (ca. 50 mL in
H2O). After washing the gel with H2O (150 mL) and removing the
nonabsorbent, the absorbent was eluted with 50% aq acetone (100
mL) and then with acetone–MeOH (4:1, 50 mL). After evaporating
the solvents from the eluate, the residual crude product was purified
by silica gel column chromatography (20:1–5:1 CHCl3–MeOH) to
afford the crude benzyl-protected acetal (127.8 mg) as a yellow oil,
which was dissolved in MeOH (2 mL). To the methanolic solution
was added 10% Pd/C (28 mg) and the mixture was vigorously
stirred at r.t. under a H2 atmosphere (balloon) for 15 h. The mixture
was filtered through a Celite pad and the filtrate was evaporated in
vacuo to afford 7 (67.2 mg, 88% from 5) as a colorless solid. Crude
7 (67.2 mg) was dissolved in MeOH (1.0 mL), and then 1,4-dioxane
(0.3 mL) and aq 6 M HCl (0.4 mL) were added to the methanolic
solution. The mixture was refluxed for 1 h. After removing the sol-
vent in vacuo, EtOH (7 mL) was added to the residue, and then the
mixture was evaporated in vacuo to remove the HCl. This procedure
was repeated twice. The residual crude 2 was acetylated with Ac2O
(0.5 mL) in pyridine (0.5 mL) in the presence of DMAP (ca. 20 mg)
at r.t. for 1 d. The mixture was added to ice-water (ca. 30mL) and
extracted with EtOAc (3 × 7 mL). The combined EtOAc extracts
MS (FAB+): m/z = 1115 (M + H)+.
Anal. Calcd for C51H54O28: C, 54.94; H, 4.88. Found: C, 54.84; H,
4.93.
Acknowledgment
We thank Mr. Hironobu Okamoto for his technical assistance.
References
(1) (a) Maurice, J. C-Glycosylflavonoids, In The Flavonoids;
Harborne, J. B., Ed.; Chapman and Hall: London, 1994, 57–
93. (b) Chopin, J.; Dellamonica, G. C-Glycosylflavonoids,
In The Flavonoids; Harborne, J. B., Ed.; Chapman and Hall:
London, 1988, 63–97.
(2) Narayanan, V.; Seshadri, T. R. Indian J. Chem. 1971, 9, 14.
(3) van Heerden, F. R.; Brandt, E. V.; Roux, D. G. J. Chem.
Soc., Perkin Trans. 1 1980, 2463.
(4) Nunes, D. S.; Haag, A.; Bestmann, H. J. Liebigs Ann. Chem.
1989, 4, 331.
Synthesis 2010, No. 18, 3126–3130 © Thieme Stuttgart · New York