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Synthesis of Antibiotics Drug-Pirlimycin
Author: TaoGuoJian
Tutor: YangYiWen
School: Zhejiang University
Course: Pharmaceutical Engineering
Keywords: Lincosamide antibiotics Pirlimycin 7-C1-MTL Hydrazinolysis Hydrogenation Chlorination
CLC: TQ465
Type: Master's thesis
Year: 2010
Downloads: 55
Quote: 0
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Abstract
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Pirlimycin (CAS No.:78822-40-9) is a lincosamide antibiotic developed by Pharmacia & Upjohn Company (now Pfizer) for the treatment of Gram-positive bacteria-induced bovine mastitis.In this thesis, a novel efficient synthetic method was reported for the preparation of pirlimycin with high purity. The synthetic procedure included the following steps:(a) the preparation of 4-ethyl-2-cyanopyridine from 4-ethyl pyridine via oxidation and cyanation; (b) the synthesis of 4-ethylpiperidine-2-carboxylic acid from 4-ethyl-2-cyanopyridine through esterification, hydrogenation, and hydrolysis reactions; (c) the protection of 4-ethylpiperidine-2-carboxylic acid with chloroformate to produce the N-substituted piperidine-2-carboxylic acid derivative; (d) the formation of 7-chloro-l-methylthio-lincosamine (7-C1-MTL) via the hydrazinolysis of lincomycin and subsequent chlorination; (e) the condensation of N-substituted piperidine-2-carboxylic acid derivatives with 7-Cl-MTL to furnish the pirlimycin intermediate; (f) the Pd/C-catalyzed hydrogenation of the pirlimycin intermediate to obtain the target product---pirlimycin.Based on cis-4-ethyl-piperidine-2-formic acid as starting material, a total yield of 37.3% was obtained with about 98% purity pirlimycin. The total yield was 26.1% when the product purity was 99%. The process has a lower cost of raw materials, more suitable for commercial production.
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CLC: > Industrial Technology > Chemical Industry > Pharmaceutical chemical industry > Antibiotics manufacture
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