US 12,195,435 B2 · 5-methylchromone and the preparation method and application thereof

Abstract

Disclosed is a 5-methylchromone and the preparation method and application thereof, the 5-methylchromone has the following structure: wherein R1 and R2 are alkyl groups. The substituted chromone has the biological activity of inhibiting tyrosinase. The preparation method uses 3,5-dihydroxytoluene as a raw material, and synthesis of chromones substituted with different groups at 2-C through acylation, esterification, rearrangement and cyclization reactions, etc. The 5-methylchromone is a completely new compound in condition that R1 is —CH2CH2CH3, and R2 is —CH2CH3, or that R1 is —C(CH3)3, and R2 is H. All the compounds have obvious inhibitory activity against tyrosinase, and can be used to prepare tyrosinase inhibitors or whitening agents.

Claims10

Dependent claims

A 5-methylchromone, having the structure shown in formula (1):

where R1 is —CH2CH2CH3 or —C(CH3)3, R2 is H or —CH2CH3;
and wherein when R1 is —CH2CH2CH3, R2 is —CH2CH3.

A preparation method of 5-methylchromone, having reaction formula:

where R1 is —CH3, —CH2CH3, —CH2CH2CH3, or —C(CH3)3;
the preparation method comprising:
dissolving the compound 1-c and the compound 1-e in the DCM, adding the DMAP, cooling to 0° C., adding the EDCI, raising to room temperature, and stirring to react;
after the reaction being completed, extracting with ethyl acetate and water, taking the organic phase, concentrating under reduced pressure, and separating and purifying the residue by column chromatography, the purification solvent A being petroleum ether and ethyl acetate, obtaining the compound 1-f;
dissolving the compound 1-f in the DMSO, adding the NaOH, and stirring to react;
after the reaction being completed, extracting with ethyl acetate and water, taking the organic phase, concentrating under reduced pressure, and separating and purifying the residue by column chromatography, the purification solvent B being petroleum ether and ethyl acetate, obtaining the compound 1-g;
dissolving compound the 1-g in the 1,4-dioxane, dripping concentrated hydrochloric acid solution, and stirring to react;
after the reaction being completed, concentrating under reduced pressure, washing the residue with dichloromethane, obtaining the target compound;
wherein
if R1 is —CH3, it is obtained for a target compound 1-1;
R1 being —CH2CH3, obtained for a target compound 1-2;
if R1 is —CH2CH2CH3, it is obtained for a compound 1-3;
R1 being —C(CH3)3, obtained for the target compound 1-4.

10 more elements

Dependencies are inferred from the claim text.

Facts

Application

17/299,631Filed 12 Mar 2021

Priority

CN 202011166791.727 Oct 2020

Published

US 2022/0324824 A113 Oct 2022

Granted

14 Jan 2025

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 311/22
Benzo[b]pyrans, not hydrogenated in the carbocyclic ring: with oxygen or sulfur atoms directly attached in position 4
A61K 8/498
With oxygen as the only hetero atom: having 6-membered rings or their condensed derivatives, e.g. coumarin
A61Q 19/02
Preparations for care of the skin: for chemically bleaching or whitening the skin
C07C 45/54
By pyrolysis, rearrangement or decomposition: of compounds containing doubly bound oxygen atoms, e.g. esters

5-methylchromone and the preparation method and application thereof

Life of this patent

5-methylchromone and the preparation method and application thereof

Life of this patent

Abstract

Claims10