Patent GB-1022745-A (GB)
Title: Substituted flavanoids and their preparation
IPC: C07D311/32
Filed: 1964-08-10
Abstract: The invention comprises compounds of the formula <FORM:1022745/C2/1> wherein R1 and R2 are OH, a substituted or unsubstituted alkoxy, alkenyloxy, aralkoxy or cycloalkyloxy group of 1-10 carbon atoms, tetrahydropyranyl - (2) - oxy, a C1-6 acyloxy group, NO2, NH2, a C1-8 alkylamino group o a C2-6 acylamino group; R3 is H, OH, C1-3 alkyl or alkoxy, NH2 or Hal (Hal is Cl, Br or I), R4 is = O; H, OH; H, H or H1 NH2; R5 is H or R1; or R2 and R5 together form a methylenedioxy, ethylenedioxy or propylenedioxy group; also the corresponding compounds having an additional double bond in the 2,3-position, provided that if R3 = H and R4 = O and there is no double bond in the 2,3-position, R5 is CH3O only if R1 is not CH3O and R2 is not CH3O or CH3OCH2O, or R1 is not NH2 and R2 is not OH, CH3O or C6H5CH2O, or R1 is not OH and R2 is not CH3O, and R2 and R5 together are methylenedioxy only if R1 is not OH or NH2, and R5 is H only if R1 is not OH, CH3 or NH2 and R2 is not CH3O, and also if R4 is = O and there is a double bond in the 2,3-position R5 is CH3O only if R1 is not NO2, R2 is not CH3O and R3 is not H or OH, and R5 is H only if R1 and R2 are not both OH or both CH3O and R3 is not H or OH, or R1 is not C2H5O, R2 is not C2H5O or CH3O and R3 is not H, or R1 and R3 are not OH and R2 is not CH3O; together with the physiologically acceptable acid addition salts and quaternary ammonium derivatives of those compounds which contain a basic nitrogen atom.  Preferred products include compounds of the above general formula wherein R1 is a group R7COCHR6O- where R6 is H or C1-5 alkyl and R7 is OH, C1-6 alkoxy, NH2, alkylated amino of 1-8 C-atoms, 2-hydroxyethylamino, pyrrolidino, piperidino or morpholino and the radical R7COCHR6O-does not contain more than 10 C-atoms, and compounds wherein R1 is OH, C1-5 alkoxy, C1-6 acyloxy or R7COCHR6O, R2 is OH, C1-5 alkoxy, C1-6 acyl, benzyloxy, dialkylaminoalkoxy or C2-4 dialkylamino, R3 is H1 OH or C1-3 alkyl or alkoxy and R5 is H or CH3O o R2 and R5 form a methylenedioxy group. The compounds are prepared by (a) cyclizing a compound of the formula <FORM:1022745/C2/2> wherein Ar is a p-R2-m-R5-phenyl group and X is -CR3=CX1-, -CHR3-CHX1- or <FORM:1022745/C2/3> X1 being hydrogen, halogen or a hydroxy or amino group, and in which any phenolic hydroxy groups may be present in a protected form; (b) cyclizing a compound of the formula <FORM:1022745/C2/4> wherein Z is -CHR3.CHAr- or -CR3 = CAr- and X is COOH, COHal, CH2OH or CH2Hal and (c) reducing suitable corresponding compounds bearing double bonds in the 2,3-or 3,4-positions or 1,2- and 3,4-positions (the ring oxygen then being in a cationic form) and/ or having reducible atoms or groups = O or H, OH in the 4-position, or conversely introducing a double bond into the 2,3-position by treating the corresponding saturated compound with a dehydrogenating agent.  The substituents R1-R5 in the products may be converted to other substituents by liberation of protected amino or hydroxy groups by hydrolysis or hydrogenolysis, alkylating or acylating a free hydroxy or amino group, reducing a nitro group to an amino group, converting a keto group in the 4-position into an amino group by oxination, followed by reduction.  Chalcones, being compounds of the Formula II above are made by condensing a 5-substituted-2-hydroxyacetophenone or propiophenone with a substituted benzaldehyde or by condensing a p-substituted phenol with a substituted cinnamic acid derivative, in the presence of aluminium chloride.  Other starting materials prepared include 4-isopropoxy-21-acetoxy - 51 - methoxy - chalcone - dibromide; 2 - hydroxy - 5 - isobutoxy - o  - methoxy - acetophenone and ethyl-p-methoxybenzoyl-acetate.  Pharmaceutical preparations having cholesterol level reducing, oestrogenic, ovario-stimulating, anti-spasmodic and/or cardio-active effects, comprise the above compounds of the invention with a physiologically acceptable carrier. The preparations may take forms adapted to parenteral, enteral or topical application such as solutions, suspensions, emulsions, implants, tablets, dragees, ointments or creams.