Rosinyl diterpene modified alpha - phosphoramidate, preparation method, and application for anti tumors

Abstract

This invention relates to a method for preparing roinyl diterpene modified alpha-aminophosphate, and its anti-tumor application. The method comprises: reacting roinyl amine diterpenoid with substituted benzaldehyde and phosphite at a mol ratio of 1 :( 1-1.05) :( 1-1.1) by solvent synthesis, one-pot synthesis or solvent-free synthesis. The inroduction of roinyl diterpene into aminophosphate can largely improve the liposolubility and bioactivity of the compound. R1 structure comes from natural product rosin, thus has low toxicity.

Description

technical field The invention relates to a derivative of rosin resin acid compound, a preparation method and its application as a medicine, in particular to a rosin-based diterpene modified α-phosphoramidate, a preparation method and an antitumor application. Background technique Amino phosphonates, as phosphorous analogs of amino acid esters, have a wide range of herbicidal, bactericidal and plant growth regulating activities. Certain amino phosphonates also have biological activities such as anticancer and antitumor and are used as starting materials to synthesize a series of phosphorus peptide. Therefore, research on the synthesis and biological activity of aminophosphonate derivatives has aroused widespread interest. (Document 1: Feio S.S.; Giganteb, C.R.; Marcelo-Curto M.J.Method on multiwell plates for the evaluation of the antimicrobial activity of resin acid derivatives[J], J.ofMicrobio.Methods.1997, 28, 201-206; Document 2: Hu Deyu, Song Baoan , Zhang Guoping, e...

AI Technical Summary

Problems solved by technology

(Document 1: Feio S.S.; Giganteb, C.R.; Marcelo-Curto M.J.Method on multiwell plates for the evaluation of the antimicrobial activity of resin acid derivatives[J], J.ofMicrobio.Methods.1997, 28, 201-206; Document 2: Hu Deyu, Song Baoan , Zhang Guoping, et al., Synthesis and crystal structure of O, O′-di-n-butyl-α-(4-trifluoromethylanilino)-2-fluorophenylphosphonate under ultrasonic irradiation[J], Organic Chemistry , 2005, 25(7), 854-858.) People try to use various synthetic methods to prepare N-terminal (nitrogen terminal), C-terminal (carbon terminal) and P-terminal (phosphorus terminal) with different substituents New derivatives of amino phosphonates, in order to find compounds with high biological activity, the N-terminal introduction of tricyclic diterpenes and groups with multiple chiral centers has not been reported in the literature

Images