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G.-Y. Gao et al. / Bioorg. Med. Chem. 11 (2003) 4069–4081
concentrated, and recrystallized from acetone to give
1.05ꢂg of crystalline 3b, a yield of 42% (w/w): mp110–
precipitated in 100 mL of ice water, collected by fil-
tration, washed with small portions of cold water, and
dried under vacuum to give 490 mg of 6 (crystalline
1
111 C. H NMR (DMSO-d6) d 1.33 (–CH3), 1.34 (–
needle), a yield of 98% (mol/mol): mp134–135 ꢂC. H
1
CH3), 4.86 (m, 1H, >CH2–), 7.05 (dd, 1H, J=8.86,
2.20 Hz, 6-H), 7.16 (d, 1H, J=2.50 Hz, 8-H), 7.38 (t,
1H, J=6.78 Hz, 40-H), 7.44 (t, 2H, J=7.76, 1.6 Hz, 30,
50-H), 7.59 (d, 2H, J=8.09, 1.6 Hz, 20, 60-H), 8.02 (d,
1H, J=8.86 Hz, 5-H), 8.46 (s, 1H, 2-H). 13C NMR
(DMSO-d6) d 21.5 (–CH3), 21.5 (–CH3), 70.4 (–CH2–O–
), 101.8 (C-8), 115.7 (C-6), 117.3 (C-10), 123.7 (C-3),
127.0 (C-10), 127.8 (C-5), 128.1 (C-30, 50), 128.9 (C-20,
60), 132.0 (C-40), 154.0 (C-2), 157.5 (C-9), 162.0 (C-7),
174.1 (C-4). MS (m/z) 281.4 (M+H)+, 303.3 (M+Na)+,
319.4 (M+K) +, 279.5 (MÀH)À. Anal. (C23H24O5) for
C, H. calcd 77.12, 5.75; found: 76.50, 5.69.
NMR (DMSO-d6) d 2.34 (–CH3), 7.33 (dd, 1H, J=8.47,
2.47 Hz, 6-H), 7.39 (m, 1H, 40-H), 7.45 (t, 2H,
J=7.75 Hz, 30, 50-H), 7.58 (d, 1H, J=2.3 Hz, 8-H), 7.60
(d, 2H, J=7.75, 1.79 Hz, 20, 60-H), 8.18 (d, 1H,
J=8.86 Hz, 5-H), 8.55 (s, 1H, 2-H). Anal. (C17H12O4)
for C, H. calcd 72.85, 4.35; found: 72.36, 4.34.
7-O-[Tetrahydro-2-(H)-pyran-2-O-propanyl]-daidzein (7a).
This compound was prepared by the same method
described for 3b except that daidzein and 2-(3-bromo-
propoxy)tetrahydro-2H-pyran were used as starting
materials. From 5.1 g of daidzein, 4.20 g of 7a (white
amorphous powder) was obtained, a yield of 82.4% (w/w):
mp112–113 ꢂC. 1H NMR (DMSO-d6) d 1.39 (m,
2H, –CH2), 1.49 (m, 2H, 300-H), 1.59–1.71 (m, 2H, 200-
H), 2.01 (m, 2H, –O–CH2–), 3.34–3.53 (m, 2H, 400-H),
3.70–3.82 (m, 2H, 500-H), 4.19 (t, 2H, –CH2–O–), 4.58
(d, 1H, J=3.62 Hz, 100-H), 6.82 (d, 2H, J=8.53, 2.59,
Hz, 30,50-H), 7.06 (dd, 1H, J=8.86, 2.42 Hz, 6-H), 7.14
(d, 1H, J=2.13 Hz, 8-H), 7.39 (d, 2H, J=8.64 Hz, 20,60-
H), 8.01 (d, 1H, J=8.88 Hz, 5-H), 8.35 (s, 1H, 2-H).
13C NMR (DMSO-d6) d 19.1 (–CH2–), 25.0 (C-300), 28.9
(C-400), 30.2 (C-200), 61.3 (C-500), 63.1 (–CH2–O–), 65.6
(–CH2–O–), 98.0 (C-100), 101.0 (C-8), 114.9 (C-6), 114.9
(C-30, 50), 117.6 (C-10), 122.4 (C-10), 123.7 (C-3), 126.9
(C-5), 130.0 (C-20, 60), 153.1 (C-2), 157.2 (C-9), 157.4 (C-
40), 162.9 (C-7), 174.7 (C-4). MS (m/z) 397.2 (M+H)+,
419.4 (M+Na)+, 435.4 (M+K)+, 395.4 (M–H)À.
Anal. (C23H24O6) for C, H. calcd 69.68, 6.10; found:
69.43, 6.08.
7-O-Ethoxycarbonylpentylisoflavone (4b). This com-
pound was prepared by the same method described for
3b except that ethyl 6-bromohexanoate was used as the
alkylating agent. From 2.52 g of 1, 3.42 g of 4b was
obtained, a yield of 85% (mol/mol): mp112–114 ꢂC;
1H NMR (DMSO-d6) d1.17 (t, 3H, –CH3), 1.45 (m,
2H, –CH2–), 1.60 (m, 2H, –CH2–), 1.77 (m, 2H, –CH2–),
2.32 (t, 2H, –CH2–), 4.05 (q, 2H, –CH2–O–), 4.12 (t,
2H, –CH2–O–), 7.07 (dd, 1H, J=8.86, 1.94 Hz, 6-H),
7.16 (d, 1H, J=1.97 Hz, 8-H), 7.38 (dd, 1H, J=7.75,
1.85 Hz, 40-H), 7.44 (d, 2H, J=7.67 Hz, 30, 50-H), 7.58
(d, 2H, J=1.94, 7.19Hz, 20, 60-H), 8.02 (d, 1H, J=8.94 Hz,
5-H), 8.47 (s, 1H, 2-H). 13C NMR (DMSO-d6) d 14.1
(–CH3), 24.2 (–CH2–), 25.0 (–CH2–), 28.1 (–CH2–), 33.4
(–CH2–), 59.7 (–CH2–O–), 68.4 (–CH2–O–), 101.1 (C-8),
115.1 (C-6), 117.5 (C-10), 123.7 (C-3), 126.9 (C-10),
127.8 (C-5), 128.1 (C-30, 50), 128.9 (C-20, 60), 132.0 (C-
40), 154.1 (C-2), 157.5 (C-9), 163.1 (C-7), 172.8
(>C¼O), 174.4 (C-4). MS (m/z) 381.5 (M+H)+, 403.6
(M+Na)+, 419.3 (M+K) +. Anal. (C23H24O5) for C,
H. calcd 72.61, 6.36; found: 72.57, 6.33.
7-O-[Tetrahydro-(2H)-pyran-2-O-]propanylisoflavone (7b).
This compound was prepared by the same method
described for 3b except that 2-(3-bromopropoxy) tetra-
hydro-2H-pyran was used as the alkylating agent. From
2.38 g of 1, 2.67 g of 7b (crystalline needle) was obtained,
7-(Hydroxyethylethoxy)ethoxyisoflavone (5b). This com-
pound was prepared by the same method described for
3b except that 2-[2-(2-chloroethoxy)ethoxy]ethanol was
used as the alkylating agent. From 2 g of 1, 280 mg of 5b
was obtained, a yield of 14% (w/w): mp105–107 ꢂC.
1H NMR (DMSO-d6) d 3.43 (m, 2H, –CH2–), 3.50 (m,
2H, –CH2–), 3.56 (m, 2H, –CH2–), 3.61 (m, 2H, –CH2–),
3.80 (m, 2H, –CH2–), 4.26 (m, 2H, –CH2–), 4.58 (t, 2H, –
CH2–), 7.10 (dd, 1H, J=8.97, 2.57 Hz, 6-H), 7.18 (d,
1H, J=2.68 Hz, 8-H), 7.37 (t, 1H, J=7.26 Hz, 40-H),
7.44 (t, 2H, J=7.75 Hz, 30, 50-H ), 7.57 (dd, 1H, J=1.60,
7.32 Hz, 20, 60-H ), 8.03 (d, 1H, J=8.88 Hz, 5-H), 8.46
(s, 1H, 2-H). 13C NMR (DMSO-d6) d 60.2 (–CH2–),
68.1 (–CH2–), 68.6 (–CH2–), 69.8 (–CH2–), 70.0 (–CH2–),
72.4 (–CH2–), 101.2 (C-8), 115.1 (C-6), 117.8 (C-10),
123.7 (C-3), 126.9 (C-10), 127.8 (C-5), 128.1 (C-30, 50),
128.9 (C-20, 60), 132.1 (C-40), 154.1 (C-2), 157.4 (C-9),
162.9 (C-7), 174.4 (C-4). MS (m/z) 371.5 (M+H)+,
393.3 (M+Na)+, 409.2 (M+K) +. Anal. (C21H22O6)
for C, H. calcd 68.10, 5.99; found: 67.92, 6.05.
a yield of 70.2% (mol/mol): mp113–115 ꢂC. H NMR
1
(DMSO-d6) d 1.41 (m, 2H, –CH2–), 1.47 (m, 2H, 300-H),
1.59–1.73 (m, 2H, 200-H), 2.0 (m, 2H, –O–CH2–), 3.40–
3.54 (m, 2H, 400-H), 3.70–3.83 (m, 2H, 500-H), 4.21 (t,
2H, –CH2–O–), 4.58 (d, 1H, J=3.5 Hz, 100-H), 7.08 (dd,
1H, J=8.9, 1.97 Hz, 6-H), 7.17 (d, 1H, J=1.97 Hz, 8-
H), 7.38 (t, 1H, J=6.98 Hz, 40-H), 7.43 (t, 2H,
J=7.38 Hz, 30, 50-H), 7.58 (d, 2H, J=7.56 Hz, 20, 60-H),
8.03 (d, 1H, J=8.88 Hz, 5-H), 8.46 (s, 1H, 2-H). 13C
NMR (DMSO-d6) d 19.1 (–CH2–), 25.0 (C-300), 28.9 (C-
400), 30.2 (C-200), 61.3 (C-500), 63.1 (–CH2–O–), 65.7 (–
CH2–O–), 98.0 (C-100), 101.1 (C-8), 115.1 (C-6), 117.6
(C-10), 123.7 (C-3), 126.96 (C-10), 127.8 (C-5), 128.1 (C-
30, 50), 128.9 (C-20, 60), 132.0 (C-40), 154.1 (C-2), 157.4
(C-9), 163.1 (C-7), 174.1 (C-4). MS (m/z) 381.4
(M+H)+, 403.4 (M+Na)+, 419.2 (M+K) +, 379.6
(MÀH)À. Anal. (C23H24O5) for C, H. calcd 72.61, 6.36;
found: 72.02, 6.34.
7-O-Acetylisoflavone (6). To a solution of 500 mg of 1 in
15 mL of anhydrous pyridine 2.0 mL of acetic anhydride
was added. The mixture was gently stirred for 6 min and
left at room temperature for 72 h. Reaction product was
7-O-(Phthalimide-N-)butyldaidzein (8a). This compound
was prepared according to the method described
before.15 To
(20.85 mmol) and 50 mL of acetone, 11 mL of 2 N KOH
a
suspension of 5.3 g of daidzein