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Wine and the French paradox
The French are 2.5 times less likely than Americans to die of coronary heart disease. Regular consumption of red wine is linked to
reduced clumping of platelets; improved cardiovascular risk profile; increased levels of HDL’s
Structural Features of Naturally Occurring Bioflavonoids
O
O
OH
O
O
O
O
Flavanone Flavone
Flavanols
O
Chalcones
Mechanisms of Bioactivity
• Flavonoids are capable of scavenging free radicals and possibly quench singlet oxygen
• Many naturally occurring flavonoids are capable of chelating metals and thereby preventing them from reducing H2O2 in hydroxyl radical formation.
• Flavonoids have a synergistic effect on vitamin C and appear to stabilize ascorbic acid in human tissues
Plant Biosynthesis of Flavonoids
HO
C
O
SCoA
HO
C
O OH
OHHOchalconesynthase
3 malonyl CoA
p-coumaroyl-CoA 4,2',4',6'-tetrahydroxychalcone
chalconeisomerase O
O
HO
OH
OH
Naringenin
O
O
HO
OH
OH
HO
O
O
HO
OH
OH
HOO
O
HO
OH
OH
HO
OH
flavonesynthase
flavonesynthase
flavonoidhydroxylase
flavonoidhydroxylase
Quercitin
Kaempferol
Reaction of Quercetin with Reaction of Quercetin with Hydroxyl RadicalsHydroxyl Radicals
.2 HO+ 2 H2O
O
O
OH
HO
OH
O
O
O
O
OH
HO
OH
OH
OH
Fe2+ + H2O2 Fe3+ + HO. + OH-
Cu2+ + HO. + OH-Cu+ + H2O2
Cu+ + Dehydroascorbic acid Ascorbic acid Cu2+
Fenton reaction
Dried peels of bitter orange treeDried peels of bitter orange tree
Naringinen-7-rhamnoglucoside
O
O
O
OH
OH
OHDisaccharide
Preparation of 2’-HydroxychalconesPreparation of 2’-Hydroxychalcones
X = H, N(CH3)2
OH O
X
C
O
CH3
OH C
O
HX
5 eq NaOH
ethanol
Preparation of Chalcones by Claisen-Schmidt Condensation
ethanol
NaOH
- H2OC
O
CH CH XC
O
CH2 CH
OH
X
C
O
HX
C
O
CH2C
O
CH3
Stereoselectivity of Condensation
HHO
C
O
HH H H
C
O
OHH
C
C6H5H
O
H
CH
C6H5
O
C6H5
- H2O
trans alkene
Cyclization of 2’-Cyclization of 2’-Hydroxychalcones to Hydroxychalcones to
FlavanolsFlavanols
CCH CH
O
OH O
O
OH
NaOHethanol
H2O2
2'-Hydroxychalcone Flavanol
Charge Distribution in Charge Distribution in 2’-Hydroxy-4-dimethylaminochalcone2’-Hydroxy-4-dimethylaminochalcone
KTaut
O OH
N(CH3)2
O OH
N(CH3)2
O OH
N(CH3)2
X MW mp ( C) IR ( CO) max ( x 10-4)
H 208.26 55 - 7 1665 312(0.89), 230 (2.67)
Cl 242.7 112 - 4 1667 325 (2.15), 313 (2.83),229 (1.45), 204 (1.86)
Br 287.2 127 - 8 1668 324 (2.02), 303 (2.49),229 (1.12), 204 (1.63)
CN 233.26 154 - 6 1671 303 (1.59), 274 (1.87),204 (1.43)
NO2 253.25 164 - 5 1672 316, 263 (2.88)
OCH3 238.28 79 - 81 1663 341 (1.18 ), 245 (2.40)
N(CH3)2 251.32 114 - 6 1656 422 (0.57), 266 (2.29),205 (1.63)
O
X
4-Dimethylaminochalcone, 4-Dimethylaminochalcone, 10-5M in methanol
190 241.667 293.333 345 396.667 448.333 5000
0.575
1.15
1.725
2.3
wavelength in nm
abso
rban
ce2.3
0.0
A1k
500190 k
200 250 300 350 400 450 5000
0.45
0.9
1.35
1.8
wavelength in nm
abso
rban
ce
1.8
0
A1k
500200 k
10-4 M DMAC in acidified methanol
Absorbances of some Chalcones Absorbances of some Chalcones in the UV and IRin the UV and IR
1633
1665
1648
1639
C=O(cm-1)X max (nm)
H
H
H
354
323
312
CH CH C
O
X
413N(CH3)2
Y
H
OH(para)
OH(ortho)
OH(para)
Y
OH(ortho)N(CH3)2 434 1619
Features of Strong Hydrogen BondingFeatures of Strong Hydrogen Bonding
• The pKa of the hydrogen donor is similar to the conjugate acid of the hydrogen acceptor;
• The energy barrier to proton transfer diminishes as the distance between the heteroatoms involved in hydrogen-bonding is reduced to value less than the sum of the van der Waals radii: < 255 pm for O-H-O and < 265 pm for O-H-N);
• H NMR chemical shifts for participating proton is far downfield (typically in the range of 16 to 20 ppm).