Galería de mapas mentales medicinal chemistry flavonoids
This is a mind map about medicinal chemistry flavonoids, including definitions, classifications, physical and chemical properties, etc. Hope this helps!
Editado a las 2023-11-24 14:29:32,flavonoids
definition
Classic: a class of compounds with a basic core of 2-phenylchromone in the structure
Now: A series of compounds formed by two benzene rings connected to each other through a central three-carbon chain, with a basic skeleton of C6-C3-C6
Classification
Flavonoids and flavonols
Flavonoids: 2-phenylchromone is the basic core, with no oxygen-containing substitution at the 3-position
Flavonols: flavonoids have a hydroxyl group or other oxygen-containing group at position 3 of the basic nucleus.
Dihydroflavones and dihydroflavonols
Dihydroflavones: The double bonds at positions 2 and 3 of the basic core of flavonoids are hydrogenated
Dihydroflavonols: Flavonols are hydrogenated at the 2 and 3 positions and often coexist with flavonols
Chalcones and dihydrochalcones
Chalcones: The three-carbon chain of flavonoids does not form a ring (under acidic conditions, chalcones can be converted into dihydroflavones)
Dihydrochalcone: Chalcone alpha, beta double bond hydrogenation
Isoflavones and dihydroisoflavones
Isoflavones: The mother core is 3-phenylchromone, and the B ring is connected to the 3rd position of the C ring.
Dihydroisoflavones: Isoflavones are hydrogenated at the 2 and 3 positions
orange ketone
Ring C is an oxygen-containing five-membered ring, and the number of carbon atoms in the parent nucleus is also different.
flavanols
No carbonyl group, divided into flavan 3-ols and flavan 3,4-ols
anthocyanin
Oxygen ions are present
Other flavonoids
Physical and chemical properties
physical properties
Form: Flavonoids are crystalline solids Flavonoid glycosides as powder
Color: ① Due to the formation of a cross-conjugated system, the conjugated chain is extended and the color appears ②The color deepens after introducing electron-donating groups such as -oH and -OCH3 at the 7-position and 4'-position. ③Dihydroflavones and dihydroflavonols do not develop color ④The color of anthocyanins is related to ph
Optical activity: ① Dihydroflavones, dihydroflavoneols, dihydroisoflavones and flavanols are optically active ②All flavonoid glycosides are optically active
Solubility: Aglycone: flavonoid aglycone is poorly soluble or insoluble in water, but soluble in organic solvents (Anthocyanins > Isoflavones, dihydroflavonols > Flavonols, Chalcones) Flavonoid glycosides: introduced sugars, more water-soluble than aglycones, 3-OH glycosides > 7-OH glycosides
The greater the number of hydroxyl groups, the greater the solubility; Hydroxymethylation, reduced solubility
chemical properties
Acidity and alkalinity
Acidic (free phenolic hydroxyl group)
The order of strength: 7,4'-dihydroxy>7- or 4'hydroxy>general phenolic hydroxyl 5-hydroxy
Basic (oxygen atoms have unshared electron pairs)
Color reaction
reduction reaction
Hydrochloric acid ~ magnesium powder reaction (flavonoids, dihydroflavones) Add hydrochloric acid first and then magnesium powder to prevent false positives
Sodium tetrahydroborate reaction (exclusive reaction for dihydroflavonoids)
Metal salt reagent complexation reaction (3-OH flavonoids, 5-OH flavonoids, o-diphenol hydroxyflavone)
magnesium acetate reaction
Zirconium salt-citric acid reaction (Determine 3-OH or 5-OH)
Adding zirconium turns yellow, with free 3- or 5-OH Add citric acid to fade 5-OH Non-fading 3-OH or o-diphenolic hydroxyl
Ammoniacal strontium chloride reaction (check o-diphenolic hydroxyl group)
Lead acetate salt reaction (o-diphenolic hydroxyl group, both 3-OH, 4=O or 5-OH, 4=O)
Boric acid color reaction (5-OH flavonoids, 6′-OH chalcone)
Alkaline reagent color reaction
Flavonols
dihydroflavones
With o-diphenolic hydroxyl substitution or 3,4'-dihydroxyl substitution
extract
Free flavonoids: less polar solvents Flavonoid glycosides and more polar aglycones: water-soluble solvents Polyglycoside: boiling water Anthocyanins: add 0.1% hydrochloric acid during extraction to inhibit ionization
Alkaline water extraction (The alkalinity should not be too strong. So as not to damage the flavonoid mother core)
dilute NaOH
Large leaching capacity, leaching many impurities
Ca(OH)2 aqueous solution
Precipitate impurities, which is beneficial to purification
separation
chromatography
Silica gel column chromatography
Elution order: flavonoid aglycones > flavonoid glycosides
Polyamide chromatography (Dual chromatography performance)
Take reverse chromatography as an example ① Glycosides, the more sugar they contain, the greater the Rf ②Aglycone has many phenolic hydroxyl groups, large adsorption capacity, and phenolic hydroxyl groups are easy to form. Intramolecular hydrogen bonds, weakened adsorption capacity
Sephadex gel chromatography
Principle: adsorption, molecular sieve action
Elution order: glycosides with more sugar > glycosides with less sugar > free aglycone
The more hydroxyl groups the aglycone has, the more difficult it is to elute; the glycoside has a large molecular weight and a large number of connected sugars, and the easier it is to elute.
Macroporous adsorption resin method
pH gradient extraction
Solvent extraction method
Identification of flavonoids
Physical and chemical examination
Color reaction, form color
Chromatographic identification
Paper chromatography detection
Thin layer chromatography detection
Better for weakly polar flavonoids
Structural research
UV spectrum
UV spectrum in methanol to understand the mother nucleus
Peak I is between 300-400, caused by B ring
Peak II is between 240-280 and is caused by the A ring
Characteristic spectrum:
Flavones and flavonols: two peaks appear, peak I and peak II have similar intensity
Peak I Flavonoids 304-350nm Flavonols 358-385nm
Chalcones and orange ketones: peak I is strong, peak II is weak, main peak band I 370-430nm
Isoflavones, dihydroflavones, dihydroflavoneols: only peak II exists
Isoflavones:II245-270nm Dihydroflavonol, dihydroflavonol: Peak II270~295nm
Add diagnostic reagent to determine hydroxyl group
Sodium methoxide (identify 4'-OH)
Band I red shift 40-65nm, intensity remains unchanged or increased
Sodium acetate (identify 7-OH)
Band II red shift 5-20nm
Sodium acetate/boric acid (determine o-diphenolic hydroxyl group)
With I red shift 12-30nm
Aluminum trichloride and aluminum trichloride/hydrochloric acid
Determination of o-diphenolic hydroxyl group AlCl3/HCl and AlCl3 comparison
AlCl3/HCl=AlCl3 No o-diphenolic hydroxyl group
Determine 3-oH, 5-OH AlCl3/HCl and compare with MeOH
Band I red-shifted 35-55nm, only 5-OH
Band I red-shifted 50-60nm, with 3-OH, 3,5-OH
NMR
1H-NMR (see ppt)
Commonly used solvents: deuterated chloroform, deuterated dimethyl sulfoxide, deuterated pyridine
Characteristics of hydroxyl groups of flavonoids
A ring proton
5,7-dihydroxyflavone
①δ5.70-6.70 ②Both hydrogens are doublets ③The coupling constants are equal ④H-6 has higher field than H-8
7-OH flavonoids
①H-5,δ7.9-8.2, ②ABX coupling (H-6 has two dipole moments, indicating the existence of ABX system) ③High field→low field:H-8>H-6>H-5
B ring proton
4'-oxygen substituted flavonoids (2', 3', 5', 6' are hydrogen)
①H-3′,5′ δ6.50-7.10 (J=8.5Hz) H-2',6' δ7.708.10 (J=8.5Hz) ②H-2'6' is in low field
3′,4′-dioxo-substituted flavonoids
①ABX coupling ②High field→low field; 5′>2'>6'
3',4'5'-trioxy oxygen-containing substitution
①If R1=R2=R3, H-2', 6' are single peaks ②If it is not true, it is a double peak.
C ring proton
Flavonoid H-3 single peak
Isoflavone H-2 δ7.6-7.8 single peak (DMSO is used as solvent, then δ8.50-8.70)