- Novel method for preparing retapamulin
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The invention provides a novel method for preparing an externally applied antibacterial medicine retapamulin. According to the method, tiamulin is used as an initial raw material, and is subjected to five steps of physical chemical reactions and a purifying process to prepare the retapamulin; the initial raw material has controllable quality, and is suitable for new medicine research, development and application; and the method is simple in operation, controllable in condition, low in preparation cost and convenient for industrial production, and is a great innovation for the retapamulin synthesis method.
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- A Swedish he Moline synthesis method
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The present invention provides a synthesis method for Retapamulin. The method comprises: using pleuromutilin as a starting material of one segment; obtaining PLM-TS by condensation reaction between the starting material and toluenesulfonyl chloride; using tropenol as a raw material of the other segment; obtaining TRP-MS by reaction between the raw material and toluenesulfonyl chloride; after performing substitution reaction between TRP-MS that uses water as a solvent and potassium ethyl xanthate, performing acidification between the substance and sulfuric acid to obtain an intermediate TRP-XAN; TRP-XAN undergoing hydrolysis in an ethanol NaOH solution; performing acidification between the substance and sulfuric acid to obtain an intermediate TRP-THI; the two segments TRP-THI and PLM-TS undergoing condensation reaction under alkaline conditions to obtain the final product, Retapamulin. The synthesis method for Retapamulin provided by the present invention is simple, environmentally friendly, easy in controlling the quality of intermediates of all steps, and suitable for the Retapamulin synthesis process in industrialized production.
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- A prepares switzerland he Moline method
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The invention discloses a method for preparing retapamulin. The method comprises the following steps that a compound of a formula 3 and a compound of a formula 4 are subjected to a nucleophilic substitution reaction to obtain a compound of a formula 5; the compound of the formula 5 is subjected to a hydrolysis reaction to obtain beta-tropine mercaptan shown in a formula 6; the beta-tropine mercaptan shown in the formula 6 is not separated and purified to be subjected to condensation with a compound of a formula 2 to obtain retapamulin 1; the reaction formula is shown in the specification, wherein M in the compound of the formula 4 is a metal ion of a potassium ion or a sodion or a calcium ion or an iron ion or an ammonium ion, n corresponds to the valence of the metal ion M and is 1 or 2 or 3, and R is alkyl groups C1-C3 or a phenyl group or a substituted phenyl group or a benzyl group or a substituted benzyl group. The method is easy and convenient to implement, a cheap reagent is adopted, the influences on the environment are greatly reduced, intermediate products are easy to purify, no column chromatography is needed, the defects of reported methods for preparing beta-tropine mercaptan and retapamulin are overcome, and the method has obvious positive and progressive effects and practical application value.
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- Process for the preparation of Retapamulin and its intermediates
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Processes for preparing tropine derivatives of the following Formula B are provided where LG represents a leaving group. The tropine derivatives may be used to prepare Retapamulin, preferably in substantially pure form. Also provided are processes for preparing Retapamulin comprising combining a base, tropine thiol in a free base or salt form, an organic solvent, and a pleuromutilin derivative of Formula A:
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Page/Page column 3; 5; 6
(2009/06/27)
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