Preparation method of anti-AIDS drug Azanavir intermediate

Abstract

The invention discloses a preparation method of an anti-AIDS drug Azanavir intermediate and belongs to the technical field of medical biology. The method comprises the steps of adjusting the secondarystructure and codon preference of a gene by means of a full-gene synthesis approach, designing the length of a primer, synthesizing the primer, dissolving the obtained primer in double-distilled water, and adding the obtained solution into a following reaction system; amplifying the prepared PCR reaction system, performing gel cutting purification on DNA fragments obtained by PCR, and selecting amonoclonal sample for sequencing, wherein a correct DNA sequence is shown as SEQ ID NO.1 and named as Sst-1, and an amino acid sequence corresponding to the DNA sequence is shown as SEQ ID NO.2. Thepreparation method has the advantages that the reaction condition is mild, the requirement for equipment is low, high temperature or cooling is not required in a production process, the energy consumption is low, purification is convenient, single-enzyme catalysis is applied in the whole system, the ratio of substrate consumption to NAD consumption reaches 1,540:1, coenzyme circulation frequency is high, and the reaction conditions are mild.

Description

technical field [0001] The invention relates to a preparation method of an atazanavir intermediate, in particular to a preparation method of an anti-AIDS drug atazanavir intermediate, belonging to the field of medical biotechnology. Background technique [0002] Atazanavir, sold under the trade name Reyataz, is an antiretroviral drug used for the treatment and prevention of HIV / AIDS. It is currently one of the main anti-AIDS drugs in the world. On the list, it is the most important drug needed by the basic health system. Bristol-Myers Squibb first developed atazanavir, which was publicly introduced in Chinese patent CN10282508C. The US FDA approved it for marketing in 2003, and China also in 2007 Approved for its listing. [0003] (2R,3S)-1-Chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol is used as a key intermediate for the preparation of atazanavir. At present, the main production processes include chemical synthesis and biosynthesis There are two methods, and the b...

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Problems solved by technology

[0007] In the process of international patent WO2011005527, due to the low enzyme activity of the enzyme used, 0.3g NAD is needed to catalyze 90 grams of substrate, and the ratio of substrate: NAD is only 300, resulting in an excessive proportion of NAD cost per kilogram of product produced , so that the production cost is high. In the Chinese patent CN102732579, Saccharomyces cerevisiae is used for whole-cell catalysis, but too many yeast cells are required (10g dry cells), and the catalytic substrate can only be completely converted when it is not greater than 0.1mM. This process production efficiency is low

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