Nov-Dec 2002
Synthesis of Novel Flavonoid Derivatives as Potential HIV- Integrase Inhibitors
1255
(s, 1H, OH); 13C nmr (deuteriochloroform): d 55.5 (CH3O at
C-4'), 55.7 (CH3O at C-6'), 56.0 (CH3O at C-3 and C-5), 60.9
(CH3O at C-4), 91.1 (C-5'), 93.8 (C-3'), 105.4 (C-2 and C-6),
106.2 (C-1'), 126.8 (a -CH=), 131.0 (C-1), 140.0 (C-4), 142.3
(b-CH=), 153.3 (C-3 and C-5), 162.3 (C-6'), 166.1 (C-2'), 168.3
(C-4'), 192.2 (-C=O). ir (potassium bromide): 1638 (C=O), 1579
106.2 (C-1'), 110.9 (C-3'), 127.3 (a -CH=), 131.2 (C-1), 139.9
(C-4), 141.8 (b-CH=), 153.3 (C-3 and C-5), 161.0 (C-6'), 163.6
(C-2'), 164.2 (C-4'), 192.7 (-C=O).ir (potassium bromide): 1628
(C=O), 1579 (C=C ar), 1555 (C=C), 1131 (C-O) cm –1
.
Anal. Calcd. for C23H28O7 (416.18) C, 66.33; H, 6.78. Found:
C, 66.06; H,6.87.
(C=C ar), 1575 (C=C), 1122 (C-O) cm –1
.
1-(3'-Butyl-2'-hydroxy-4',6'-dimethoxyphenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (24).
Anal. Calcd. for C20H22O7 (374.38): C, 64.16; H, 5.92. Found:
C, 64.28, H, 6.15.
Compound partially crystallized after cooling the reaction
mixture to room temperature. The rest of it was recovered after
partial evaporation of the liquid. Crystallized from ethanol giv-
ing yellow crystals; yield 62%; mp 149-150 °C; 1H nmr (deuteri-
ochloroform): d 0.84-0.95 (t, J=7.3 Hz, 3H, CH2CH2CH2CH3),
1.30-1.5 (m, 4H, CH2CH2CH2CH3), 3.82, 3.86, 3.87, 3.88, 3.92
(s, 15H, CH3O), 5.97 (s, 1H, Ar), 6.81 (s, 2H, Ar), 7.63-7.78 (dd,
J=15.6 Hz, 2H,-CH=CH-), 13.9 (s, 1H, OH); 13C nmr (deuteri-
ochloroform): d 14.1 ( CH3CH2CH2CH2 at C-3'), 22.7
(CH3CH2CH2CH2 at C-3'), 23.0 (CH3CH2CH2CH2 at C-3'), 31.7
(CH3CH2CH2CH2 at C-3'), 55.5 (CH3O at C-4'), 55.7 (CH3O at
C-6'), 56.0 (CH3O at C-3 and C-5), 60.9 (CH3O at C-4), 86.4
(C-5'), 105.4 (C-2 and C-6), 106.3 (C-1'), 109.8 (C-3'), 127.4 (a -
CH=), 131.2 (C-1), 139.9 (C-4), 141.8 (b-CH=), 153.3 (C-3 and
C-5), 161.0 (C-6'), 163.5 (C-2'), 164.2 (C-4'), 192.7 (-C=O). ir
(potassium bromide): 1628 (C=O), 1578 (C=C ar), 1570 (C=C),
1-(2'-Hydroxy-4',6'-dimethoxy-3'-methylphenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (21).
This compound crystallized from the reaction mixture as pale
yellow crystals. It was recrystallized from ethanol and finally
purified on a Chromatotron instrument thus giving 60% product;
mp 188-189 °C; 1H nmr (deuteriochloroform): d 2.03 (s, 3H,
-CH3), 3.88, 3.89, 3.90, 3.93 (s, 15H, CH3O), 5.99 (s, 1H, Ar),
6.82 (s, 2H, Ar), 7.64-7.80 (dd, J= 15.6 Hz, 2H), 14.04 (s, 1H,
OH). 13C nmr (deuteriochloroform): d 7.2 (CH3 at C-3'), 55.4
(CH3O at C-4'), 55.7 (CH3O at C-6'), 56.1 (CH3O at C-3 and
C-5), 60.9 (CH3O at C-4), 86.3 (C-5'), 105.4 (C-2 and C-6),
106.0 (C-1'), 106.2 (C-3'), 127.2 (a -CH=), 131.2 (C-1), 139.9
(C-4), 141.9 (b-CH=), 153.3 (C-3 and C-5), 160.9 (C-6'), 163.5
(C-2'), 164.2 (C-4'), 192.7 (-C=O). ir (potassium bromide): 1631
(C=O), 1580 (C=C ar), 1572 (C=C), 1125 (C-O) cm –1
.
1132 (C-O) cm –1
.
Anal. Calcd. for C21H24O7 (388.15): C, 64.94; H, 6.23. Found:
C, 64.85, H, 6.33.
Anal. Calcd. for C24H30O7(430.20): C, 66.96; H, 7.02. Found:
C,66.56; H,7.10.
1-(3'-Ethyl-2'-hydroxy-4',6'-dimethoxyphenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (22).
1-(2'-Hydroxy-4',6'-dimethoxy-3'-pentylphenyl)- 3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (25).
The compound was obtained after concentrating the reaction
mixture under vacuum and addition of water as yellow oil, which
crystallized from ethanol; yield 60%. mp 172-173 °C; H nmr
After evaporation of the reaction mixture, yellow oil was col-
lected and dissolved in ethanol. Yellow crystals with 65% yield;
mp 145-146 °C; 1H nmr (deuteriochloroform): d 0.85-0.90 (t,
J=6.7 Hz, 3H, CH2CH2CH2CH2CH3), 1.29-1.49 (m, 6H,
CH2CH2CH2CH2CH3 ), 2.54-2.59 (t, J= 7.3 Hz, 2H, CH2CH2-
CH2CH2CH3), 3.88, 3.89, 3.92 (s, 15H, CH3O), 7.63-7.79 (dd,
J=15.3, 2H, CH=CH-), 13.9 (s, 1H, OH); 13C nmr (deuteriochlo-
roform): d 14.1 (CH3CH2CH2CH2CH2 at C-3'), 22.2 (CH3CH2-
CH2CH2CH2 at C-3'), 22.6 (CH3CH2CH2CH2CH2 at C-3'), 28.7
(CH3CH2CH2CH2CH2 at C-3'), 31.9 (CH3CH2CH2CH2CH2 at
C-3'), 55.5 (CH3O at C-4'), 55.7 (CH3O at C-6'), 56.1 (CH3O at
C-3 and C-5), 60.9 (CH3O at C-4), 86.4 (C-5'), 105.4 (C-2 and
C-6), 106.4 (C-1'), 111.3 (C-3'), 127.4 (a -CH=), 131.2 (C-1),
139.9 (C-4), 141.9 (b-CH=), 153.4 (C-3 and C-5), 161.0 (C-6'),
163.5 (C-2'), 164.2 (C-4'), 192.8 (-C=O). ir (potassium bromide):
1
(deuteriochloroform): d 1.04-1.10 (t, J=7.3 Hz, 3H, -CH2CH3),
2.58-2.65 (q, J=7.3 Hz, 2H, -CH2CH3), 3.89, 3.90, 3.91, 3.94 (s,
15H, CH3O), 6.00 (s, 1H, Ar), 6.84 (s, 2H, Ar), 7.66-7.80 (dd,
J=15.0 Hz, 2H, -CH=CH-), 9.80 (s, 1H, OH); 13C nmr (deuterio-
chloroform): d 13.4 (CH3CH2 at C-3'), 15.5 (CH3CH2 at C-3'),
55.4 (CH3O at C-4'), 55.7 (CH3O at C-6'), 56.0 (CH3O at C-3 and
C-5), 60.9 (CH3O at C-4), 86.4 (C-5'), 105.4 (C-2 and C-6),
106.3 (C-1'), 112.4 (C-3'), 127.3 (a -CH=), 131.2 (C-1), 139.9
(C-4), 141.9 (b-CH=), 153.3 (C-3 and C-5), 161.0 (C-6'), 163.3
(C-2'), 164.0 (C-4'), 192.7 (-C=O). ir (potassium bromide): 1635
(C=O), 1582 (C=C), 1559 (C=C ar), 1128 (C-O) cm –1
.
Anal. Calcd. for C22H26O7 (402.17): C, 65.66; H, 6.51. Found:
C,65.58, H, 6.60.
1629 (C=O), 1578 (C=C ar), 1570 (C=C), 1132 (C-O) cm –1
Anal. Calcd. for C25H32O7 (444.21): C, 67.55; H, 7.26. Found:
C, 67.57, H, 7.42.
.
1-(2'-Hydroxy-4',6'-dimethoxy-3'-propylphenyl)-3-(3,4,5-
trimethoxyphenyl)prop-2-en-1-one (23).
The compound was obtained as yellow oil after addition of
water and concentration of the reaction mixture under vacuum.
The oil was dissolved in ethanol and the yellow precipitate was
collected; yield 65%. mp 171-172 °C; 1H nmr (deuteriochloro-
form): d 0.87- 0.92 (t, J=7.3 Hz, 3H, -CH2CH2CH3), 1.45-1.54
(m, 2H, CH2CH2CH3), 2.52-2.58 (t, J=7.3 Hz, 2H,
CH2CH2CH3), 3.85, 3.86, 3.90 (s, 15H, CH3O), 5.98 (s, 1H, Ar),
6.82 (s, 2H, Ar), 7.61-7.76 (dd, J=15.6 Hz, 2H, -CH=CH-), 13.93
(s, 1H, OH); 13C nmr (deuteriochloroform): d 14.1 (CH3CH2CH2
at C-3'), 22.1 (CH3CH2CH2 at C-3'), 24.2 (CH3CH2CH2 at C-3'),
55.4 (CH3O at C-4'), 55.7 (CH3O at C-6'), 56.1 (CH3O at C-3 and
5,7-Dimethoxy-2-(3',4',5'-trimethoxyphenyl)-4H-chromen-4-one
(26).
The dark brown precipitate obtained from the mother liquid
was first recrystallized from ethanol to give 50% yield of a pale
brownish solid. mp198-199 °C; 1H nmr (deuteriochloroform): d
3.90, 3.91, 3.93, 3.94 (s, 15 H, -CH3O), 6.36-6.37 (d, J=2.4 Hz,
1H, Ar), 6.55-6.56 (d, J=2.4 Hz, 1H, Ar), 6.66 (s, 1H, O=C-
CH=), 7.06 (s, 2H, Ar); 13C nmr (deuteriochloroform): d 55.7
(CH3O at C-7), 56.2 (CH3O at C-3'+C5'), 56.3 (CH3O at C-5),
60.9 (CH3O at C-4'), 92.8 (C-8), 96.1 (C-6), 103.2 (C2'+C6'),
108.6 (C-3), 109.0 (C-10), 126.6 (C-1'), 140.7 (C-4'), 153.4
C-5), 60.9 (CH O at C-4), 86.3 (C-5'), 105.4 (C-2 and C-6)
,
3