The invention relates to a preparation method of
valnemulin hydrochloride. The preparation method comprises the following steps: reacting
pleuromutilin with p-toluenesulfonyl
chloride, substituting with 1-amino-2-methyl propyl-2-mercaptan
hydrochloride so as to obtain [(2-amino-1,1-dimethyl S, 6S, 8R,9R, 9aR, 10R)-6-vinyl decahydro-5-hydroxyl-4,6,9,10-tertamethyl-1-oxo-3a, 9-
propanol-3aH-cyclopentacyclooctene-8-yl ester for later use; reacting D-
valine with
methyl acetoacetate; synthesizing the product with isobutyl chloroacetate so as to generate anhydride; and reacting anhydride with [(2-amino-1,1-dimethyl ethyl) sulfenyl]
acetic acid (3aS, 4R, 5, 6S, 8R,9R, 9aR, 10R)-6-vinyl decahydro-5-hydroxyl-4,6,9,10-tertamethyl-1-oxo-3a, 9-
propanol-3aH-cyclopentacyclooctene-8-yl ester so as to generate
amide, and then carrying out deprotection with
hydrochloric acid so as to prepare
valnemulin hydrochloride. The method has the advantages that (1)
reaction temperature is mild, thereby being applicable to large-scale production; (2) post-treatment is simple, thereby directly obtaining the product; (3) used solvents are less, thereby reducing environmental
pollution; and (4) the
valnemulin hydrochloride content and yield of the obtained product are high.