Preparation method for ubenimex

Abstract

The invention belongs to the field of antineoplastic agent preparation and provides a preparation method for ubenimex. The preparation method comprises the following steps of: preparing high-purity key intermediate (2S,3R)-3-amino-2-hydroxy-4-phenyl butyric acid by taking L-lysine, L-arginine or L-histidine as a resolving reagent; and preserving the chirality of C-5 in forming a peptide chain by taking EDCI / HOAt as a condensing agent. Due to the adoption of the method, the problem that the (2S,3R)-3-amino-2-hydroxy-4-phenyl butyric acid and the (2S,3R)-3-acetamino-2-hydroxy-4-phenyl butyric acid cannot be completely separated by the conventional resolving agent and the racemization problem in the condensation of amide are effectively solved; and the purity of the ubenimex prepared by the method can reach over 99.5 percent.

Description

technical field

[0001] The invention belongs to the field of preparation of antitumor drugs, and in particular relates to a preparation method of ubenimex. Background technique

[0002] Ubenimex, the chemical name is N-[(2S,3R)-4-phenyl-3-amino-2-hydroxybutyryl]-L-leucine, and its structure is shown in 1-a.

[0003]

[0004] Formula 1-a

[0005] Ubenimex is a peptide anti-tumor drug, which was discovered by H. Umezawa (US 4052449) et al. from the fermentation broth of Streptomyces olivine reticulum. It can promote the body's immune response and inhibit aminopeptidase B and leucine aminopeptidase.

[0006] Clinical studies have shown that Ubenimex achieves its curative effect in cancer treatment by enhancing the cytotoxic activity of known antineoplastic drugs. This product is used for the adjuvant treatment of chemotherapy and radiotherapy of tumor patients and diseases such as senile immunodeficiency. Indications include leukemia, multiple...

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