A kind of method for preparing optically active α-hydroxy-β-amino acid compounds

Abstract

The invention discloses a method for preparing an optically active N-acyl-α-hydroxyl-β-amino ester compound shown in formula II in one pot from an α-acyloxy-β-enamine ester compound. The method uses A novel six-membered cyclic pyridinecarboxamide-sulfonate Lewis base (compound of formula III), which has shown good catalytic activity, high diastereoselectivity and enantioselectivity, can be utilized for this compound A series of optically active N-acyl-α-hydroxy-β-amino esters were successfully obtained through a one-pot reaction.

Description

technical field [0001] The invention relates to a method for preparing optically active α-hydroxyl-β-amino acid compounds. Background technique [0002] Optically active α-hydroxy-β-amino acid is a very important structural unit, which widely exists in natural products and drug molecules, the most famous of which are anticancer drugs paclitaxel, ubenimex, glycopeptide Dideoxykanamicin A, etc. Therefore, the synthesis of optically active α-hydroxy-β-amino acid derivatives has attracted extensive and lasting interest. Over the years, many research groups have developed a variety of efficient and highly selective synthetic methods, mainly including Sharpless asymmetric hydroxylamination and Dihydroxylation reaction, ring-opening reaction of chiral epoxy compounds, asymmetric nitro-Aldol reaction, asymmetric Mannich reaction, 1,3-dipolar cycloaddition reaction and other reactions. However, there are few reports on obtaining optically active α-hydroxy-β-amino acid derivatives by...

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Problems solved by technology

[0007] Although the inventors succeeded in synthesizing optically active α-hydroxy-β-amino acid derivatives by chiral Lewis base-catalyzed asymmetric hydrosilylation of N-aryl-α-acetoxy-β-enamino esters, This method also has the following disadvantages: 1, the synthesis of the reaction substrate is difficult, the synthetic route is long, the conditions are harsh, the yield is low, and the scope of application is not wide, the α position can only be an acetoxy group, and the slightly larger acyl group cannot Obtain; 2. When the reaction product is converted into paclitaxel side chain molecules, it will go through three steps of deacetylation, de-p-methoxyphenyl, and benzoylation, and there are long reaction steps, cumbersome operations, and difficulties in handling intermediate products , the problem of low efficiency (Formula B)

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