Total synthesis method of optically pure tetrandrine

Abstract

The invention discloses a total synthesis method of optically pure tetrandrine, and belongs to the technical field of drug synthesis. The method comprises the following steps: (1) under the action ofa catalyst (1), carrying out intermolecular Ullmann reaction on a compound (1) and a compound (2) under alkaline and high-temperature conditions to synthesize a compound 3; (2) removing a hydroxyl protecting group from the compound (3) under an acidic condition to synthesize a compound (4); (3) carrying out intramolecular Ullmann reaction on the compound (4) under the action of a catalyst (2) under alkaline and high-temperature conditions to synthesize a compound (5), namely the optically pure tetrandrine. A convergent synthesis strategy is adopted, and only three steps are needed from the compound (1) to the synthesis of optically pure tetrandrine so that the reaction steps are greatly reduced, and the time and the material cost are saved; the yield can be as high as 28.7%-38.9%, and theyield is increased by dozens of times; the target product can be obtained on the gram scale, 1.3 g-1. 5 g of final optically pure product is synthesized, and the method has better industrialization potential.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a total synthesis method of optically pure tetrandrine. Background technique [0002] Tetrandrine is an alkaloid extracted from the root of Tetrandrine, a plant of the family Tetrandrine. Its structure is as follows, [0003] [0004] It has many pharmacological effects, such as antipyretic, analgesic, anti-inflammatory, diuretic, antihypertensive, etc. Many literatures have reported that tetrandrine also has inhibitory activity on various tumor cells, such as liver cancer, lung cancer, gastric cancer, prostate cancer, breast cancer and so on. [0005] At present, tetrandrine is generally produced by extracting and separating the roots of tetrandrine. However, the total alkaloid content in tetrandrine root is 1.5-2.3%, while the content of tetrandrine is about 1%. Therefore, the production of tetrandrine by extracting from the root of tetrandrine has the following di...

AI Technical Summary

Problems solved by technology

Therefore, the production of tetrandrine by extracting from the roots of tetrandrine has the following disadvantages: 1. The demand for the raw material tetrandrine is large and the production is limited, resulting in a shortage of supply in the market; 2. The extraction process is complicated, the production efficiency is low and the cost is low. 3. The amount of production waste is large and the pressure on environmental protection is high

[0008] The biological activity of racemic tetrandrine is low, so our ultimate goal is to develop optically pure tetrandrine; on the basis of economical and efficient synthesis of racemic tetrandrine, develop optically pure tetrandrine The synthetic method of tetrandrine is of great significance to the development of the chemical synthesis and production process of tetrandrine

Images