US 12,735,384 B2 · Methods for preparing (2S,3R,4R)-4,5-dihydroxyisoleucine derivative and intermediates thereof

Abstract

Provided are methods for preparing a (2S,3R,4R)-4,5-dihydroxyisoleucine (DHile) derivative and intermediates thereof. Methods for preparing a series of intermediates of the (2S,3R,4R)-4,5-DHile derivative are provided, on the basis of which the (2S,3R,4R)-4,5-DHile derivative could be prepared. Specifically, a glycine derivative, benzophenone imine glycine tert-butyl ester (compound 1, with a structure shown in Formula 1) that is easy to be purchased through commercial channels and has a low price, is selected as a starting reaction raw material; the starting reaction raw material is subjected to asymmetric allylation, asymmetric dihydroxylation, and introduction or removal of protective groups to achieve efficient asymmetric synthesis of a target product.

Claims4

Dependent claims

A method for preparing an intermediate A of a (2S,3R,4R)-4,5-dihydroxyisoleucine (DHile) derivative, comprising the following steps:

subjecting a compound 1 with 3-chlorobut-1-ene to asymmetric allylation to obtain the intermediate A of the (2S,3R,4R)-4,5-DHile derivative;
wherein the compound 1 has a structure shown in Formula 1, and the intermediate A of the (2S,3R,4R)-4,5-DHile derivative has a structure shown in Formula 2:
the asymmetric allylation is conducted in the presence of a rhodium catalyst, a rhodium catalyst ligand, a copper catalyst, a copper catalyst ligand, and an alkaline reagent;
the rhodium catalyst is [Rh(COD)C1]2, the copper catalyst is Cu (CH3CN)4PF6, and the alkaline reagent is potassium phosphate;
the rhodium catalyst ligand has a structure shown below:
and
the copper catalyst ligand has a structure shown below:
and
the asymmetric allylation is conducted at a temperature of −10° C. to 25° C. for 12 hours to 24 hours.

6 more elements

Dependencies are inferred from the claim text.

Methods for preparing (2S,3R,4R)-4,5-dihydroxyisoleucine derivative and intermediates thereof

Life of this patent

Methods for preparing (2S,3R,4R)-4,5-dihydroxyisoleucine derivative and intermediates thereof

Life of this patent

Abstract

Claims4