Preparation method of combretastatin furan type analogues

Abstract

The invention provides a preparation method of combretastatin furan type analogues. The preparation method of the combretastatin furan type analogues (A and C) comprises the following steps of adding a solvent 1, a compound P1 and 3,4,5-triethoxy benzaldehyde into a reaction flask; adding alkali while stirring; reacting for 10 minutes at room temperature; adding diluted acid to regulate pH (Potential of Hydrogen) to be neutral; obtaining the combretastatin furan type analogue C through separation and purification; obtaining a compound A by reducing the C in a solvent 2 by using Raney Ni. The preparation method of combretastatin furan type analogues (B and D) comprises the following steps of adding the solvent 1, a compound P2 and 3-trimethylsilyl ether-4-methoxybenzaldehyde into the reaction flask; adding alkali while stirring; reacting for 10 minutes at the room temperature; adding the diluted acid to regulate pH (Potential of Hydrogen) to be neutral; obtaining the combretastatin furan type analogue D through separation and purification; obtaining a compound B by reducing the D in the solvent 2 by using the Raney Ni. The preparation method of the combretastatin furan type analogues, provided by the invention, has the advantages that the yield is high, the operation is simple, the reaction conditions are moderate, the used solvents are cheap and easy to get, industrial production is easy to realize, and the like.

Description

technical field [0001] The invention belongs to the field of medicines, in particular to a preparation method of combretastatin furan analogs Background technique [0002] Combretastatin is an anti-tumor drug targeting tumor blood vessels, which can quickly and selectively induce the collapse of existing blood vessels inside tumor tissues, block blood supply, and cause ischemic necrosis of tumor tissues. Sewan Theeramunkong et al. described in the literature (J. Med. Chem. 2011, 54, 4977-4986) the determination of the biological activity of combretastatin furan analogs A and B using neuroblastoma cell lines. The results showed that both A and B could inhibit cell survival and growth, exhibit similar cytotoxicity in HeLa cells, and induce severe G 2 / M block, eventually leading to cell death. In addition, the sulfur-containing groups connected to the furan ring on the precursor compounds C and D are beneficial to increase water solubility, introduce complex groups, and be l...

AI Technical Summary

Problems solved by technology

[0007] The raw materials of this type of method are expensive and difficult to prepare, and the Pd(PPh 3 ) 4 It is also relatively expensive and may lead to heavy metal residues, cumbersome operation, and unsatisfactory product yield

Images