Note : ONLY CANDIDATES WILLING TO MOVE TO CHINA SHOULD APPLY

Location: Zhejiang Province. Hangzhou and the surrounding area

Project Name: A new method for structural modification of steroid compounds.

Client : Zhejiang Xianju Pharmaceutical Co. Ltd.

Industry : Pharmaceutical Manufacturing

Unit Information (client information, main areas of activity,project background etc.):

Zhejiang Xianju Pharmaceutical Co., ltd. formerly known as Xianju Pharmaceutical factory, is the largest, most complete domestic steroid drug manufacturers, owning the reputation as the national family planning fixed-point manufacturers, national torch plan key high-tech enterprise, national guard contract, heavy credit enterprise, top 10 API export-oriented brand enterprise in China, top 100 Chinese chemical Pharmaceutical brand, etc. The company has a registered capital of 6,10808,111 yuan, total assets of more than 3 billion yuan, covering an area of 648.65 acre, and more than 3,000 employees, among which 15% are technicians and 35% are sales personnel.

Nature of Activity Requested for Experts (Project description, assignment target, etc.)-

Description-

The structural modification of steroid compounds generally adopts the traditional synthesis method, but the oxidation reaction of hydroxyl group, the C11 methylenation reaction, the elimination of C3 hydroxyl group and other structural modification of steroid compounds have the problems of big pollution, many by-products and high cost, so new methods should be developed to solve these problems.

Issues to solve :

1. Oxidation reaction development in environment friendly way () 

The oxidation reaction commonly used in industrial production are Jones oxidation, PCC oxidation, Mr Wolfowitz oxidation and hypochlorite oxidation (or in situ generated hypochlorite in original position). but Jones oxidation and PCC oxidation generate heavy pollution, Mr Wolfowitz oxidation needs heavy workload during post-treatment, and hypochlorite oxidation applicability is low. We need to check if we can develop a new oxidation reaction with the advantage of green, no pollution, mild reaction, the substrate wide adaptability, catalyst used can be recycled for industrial production.

2. Methylene was introduced into the steroid at C11 :

Due to steric hindrance, methylene cannot be introduced by witting reaction, which is the most common way to construct methylene. After elimination by methyl Grignard reagent, the by-products of multiple isomers will be generated, so how to introduce methylene at C11 steroidal structure is an issue.

3. Selectivity of 3 - position hydroxyl elimination :

In addition to the target 2, 3 elimination products (approximately 80%), 3, 4 elimination by-products (approximately 20%) were obtained. None of the methods reported in the present literature can reduce the proportion of by-products, so it is difficult to improve the selectivity of elimination of 3-position hydroxyl groups.

Statistics & Data :

1. Green oxidation reaction development

Green, pollution-free, mild reaction, wide substrate adaptability, catalyst can be simply recycled for industrial production of new oxidation reaction, excipient cost less than 50 yuan/kg, molar yield> 95%, single impurity 98%.

2. Methylene introduced into C11 steroid structure

The methylene reaction with advantage of mild reaction, high safety, good selectivity and low cost is situatable for industrial production. The excipient cost is less than 200 yuan/kg. Molar yield> 90%, single impurity< 1.0% and the purity> 90%.

3.Selectivity of 3-position hydroxyl elimination

Mild reaction, high safety, good selectivity, low cost, suitable for industrial production. Excipient cost< 100 yuan/kg, molar >95%, 3, 4 elimination by-products < 5%, other single impurity < 0.5%, purity > 95%.

Expert qualification required (Professional, degree, language, experience, etc) and assignment target date, duration and location-

Major : organic synthesis

Degree : doctor

Language : Chinese or English

Priority will be given to r&d leaders of companies like Pfizer inc. GSK- CHEMO- Boehringer-Ingelheim- BAYER- Novartis- MSD

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