Preparation method of mould cell catalyst for catalyzing synthetic reaction of cytarabine ocfosfate

Abstract

The invention discloses a preparation method of a mould cell catalyst for catalyzing synthetic reaction of cytarabine ocfosfate. The method comprises the following steps of: inoculating mould spores into a liquid basal culture medium containing an enzyme production inducer with the concentration of 0.5g / L-50g / L, wherein the inoculum concentration is 1*103-1*1012 mould spores / L, the culture condition is 10 DEG C-45 DEG C and the culture time is 10 hours-200 hours; collecting thalli, washing with distilled water or a buffer solution, then washing with acetone for 1-3 times, and performing suction filtration on the thalli to obtain the mould cell catalyst for catalyzing synthetic reaction of cytarabine ocfosfate; or removing water by a lyophilizing method to obtain the mould cell catalyst for catalyzing synthetic reaction of cytarabine ocfosfate. The mould cell catalyst disclosed by the invention has the advantages of low cost, easiness of preparation, environmental friendliness and high catalyst activity.

Description

technical field

[0001] The invention belongs to the fields of microorganism cultivation, biocatalysis and biomedicine preparation, and relates to a method for preparing a mold cell catalyst that catalyzes the synthesis reaction of cytarabine ester. Background technique

[0002] Cytarabine is a class of unnatural nucleosides, belonging to deoxycytidine analogues, has high anti-leukemia activity, and is one of the most effective chemotherapy drugs clinically used for the treatment of acute myeloid leukemia. However, it has the disadvantages of low oral availability, short half-life, and large toxic and side effects in clinical practice. Cytarabine ester is one of the prodrugs of cytarabine, which is obtained by acylation of the hydroxyl group of the sugar moiety of cytarabine. Pharmacological test results show that cytarabine ester derivatives are more suitable for the treatment of systemic or local malignant tumors than cytarabine itself, especially for malignant tumors in t...

Examples

Embodiment 1

[0024] The regioselectivity of the catalyst obtained by the method of the present invention is determined by the regioselective acylation reaction of cytarabine and vinyl acetate, and the reaction condition is to add 0.05g of dry bacteria to the cytarabine esterification reaction system of 1mL Silk was used as a catalyst, the dosage of cytarabine was 5 mg, the reaction system was 75% (v / v) pyridine-n-hexane, the reaction temperature was 30°C, the shaking speed was 180 rpm, and the reaction was carried out under normal pressure for 24 hours. The reaction regioselectivity is characterized by: the yield of 3'-cytarabine ethyl ester / the total yield of cytarabine ester.

[0025] Example 2

Embodiment 2

[0027] Example 3

Embodiment 3

[0029] Example 4

technical field

[0001] The invention belongs to the fields of microorganism cultivation, biocatalysis and biomedicine preparation, and relates to a method for preparing a mold cell catalyst that catalyzes the synthesis reaction of cytarabine ester. Background technique

[0002] Cytarabine is a class of unnatural nucleosides, belonging to deoxycytidine analogues, has high anti-leukemia activity, and is one of the most effective chemotherapy drugs clinically used for the treatment of acute myeloid leukemia. However, it has the disadvantages of low oral availability, short half-life, and large toxic and side effects in clinical practice. Cytarabine ester is one of the prodrugs of cytarabine, which is obtained by acylation of the hydroxyl group of the sugar moiety of cytarabine. Pharmacological test results show that cytarabine ester derivatives are more suitable for the treatment of systemic or local malignant tumors than cytarabine itself, especially for malignant tumors in t...

Examples

Embodiment 1

[0024] The regioselectivity of the catalyst obtained by the method of the present invention is determined by the regioselective acylation reaction of cytarabine and vinyl acetate, and the reaction condition is to add 0.05g of dry bacteria to the cytarabine esterification reaction system of 1mL Silk was used as a catalyst, the dosage of cytarabine was 5 mg, the reaction system was 75% (v / v) pyridine-n-hexane, the reaction temperature was 30°C, the shaking speed was 180 rpm, and the reaction was carried out under normal pressure for 24 hours. The reaction regioselectivity is characterized by: the yield of 3'-cytarabine ethyl ester / the total yield of cytarabine ester.

[0025] Example 2

Embodiment 2

[0027] Example 3

Embodiment 3

[0029] Example 4