A kind of preparation method of α, β-diaminic acid derivative of α-position quaternary carbon

Abstract

The invention relates to a preparation method of α, β-diamic acid derivatives with α-position quaternary carbon. Using diazo, alkoxyamide, and imine as raw materials, rhodium acetate, chiral phosphoric acid and acid additives as catalysts, and molecular sieves as water-absorbing agents for one-step asymmetric catalysis, different substituted chiral phosphoric acids can catalyze reactions selectively including ( 2R, 3R)-trans-IIA, (2R, 3S)-cis-IIB, (2S, 3S)-trans-IIC and (2S, 3R)-cis-IID target product α-position quaternary carbon α,β-Diamino acid derivatives. The application of the present invention is to use II as a raw material to prepare a pharmaceutically active intermediate (imidazoline derivative IV containing quaternary carbon). The invention has the advantages of simple and easy-to-obtain raw materials, simple and safe operation, high atom economy, high yield and high selectivity. The method can conveniently and simultaneously obtain the α,β-diamine derivatives of the cis or trans α-position quaternary carbon, provide a variety of compound skeletons, and have very important significance for new drug screening and pharmaceutical technology.

Description

technical field The invention relates to a preparation method of an α, β-diaminic acid derivative with an α-quaternary carbon, which has optical activity and belongs to the technical field of pharmaceutical synthesis chemistry . Background technique Optically active α, β-diaminic acid derivatives are a class of important skeleton structures with special medicinal compounds. They are used in anti-lymphoma drug bleomycin, anti-tuberculosis drug capreomycin, purple This kind of skeleton structure is found in structures such as viomycin. A series of α, the synthetic method of β-diaminic acid derivatives developed in recent years complement each other and improve (Chem.Rev.2005,105,3167., Org.Biomol.Chem., 2005,3,1362., J. Am. Chem. Soc., 2008, 130, 2170.). Most of the existing methods for synthesizing α, β-diaminic acid derivatives are obtained through the Mannich reaction of glycine esters and imines. However, the biggest defect of this type of method is that only cis-confi...

AI Technical Summary

Problems solved by technology

Most of the existing methods for synthesizing α, β-diaminic acid derivatives are obtained through the Mannich reaction of glycine esters and imines. However, the biggest defect of this type of method is that only cis-configuration α can be selectively obtained, β-Diamino acid derivatives

Most modern high-selectivity asymmetric synthesis methods focus on the synthesis of one or a group of enantiomers with high diastereoselectivity and high enantioselectivity, while for the synthesis of other diastereomers of target molecules Often have to rely on other catalytic methods, or can't do anything