The Synthesis Study Of Cefquinome Sulfate And Eplerenone

PART ICefquinome, the4th grade cephalosporin antibiotics with broad antibacterial range and highly antibacterial activity, shows nicer antibacterial activity to G+and G-, especially shows great stability to β-lactam enzyme. It has been used to cure respiratory infection of cattle and pig, and mastitis of milch cow.This paper is concerned on the synthesis route of sulfate cefquinome and its optimize technics.Method A:Cefquinome sulfate is prepared from Cefotaxime via3-substitution, salt formation, salt exchange with sulfuric acid by anion exchange resin. The total yield of cefquinome sulfate is35.9%, its structure has been confirmed by’H-NMR. The synthetic route for cefquinome sulfate is convenient for raw materials availability and industrial manufacture. Method B is complicated with low yield, which is not proper to be enlarged.Each reaction is discussed. Trimethyliodosilane is obtained by reaction of hexamethyldisilane and iodine with short reaction time, highly transformation and no byproduct presence. The method of separation is improved in acetone and acetonitrile, which crude yield is85%. The product can be used for the next reaction without purification. Amberlite LA-2can be replaced by717-alkalescence anion exchange resin to neutralize hydrogen iodide of cefquinome hydrogen iodate with good result and the yield is53.9%.PART ⅡEplerenone, a selective andosterone blocker, is developed for the treatment of hypertension and congestive heart failure.The paper is a study about the synthesis of Eplerenone. Based on the analysis of the synthesis described in the reference, we choose11α-hydroxycanrenone as the starting material, and get the target material eplerenone via7-substitution with2-methylfuran,9,11-dehydration, furan ring-opening, ozonation, methylation and double bond epoxidation.11α-hydroxycanrenone and2-methylfuran undergo7-nucleophilic substitution with highly stereoselectivity which is7α/β=99/1and the yield is more than80%. Ethanesulfonyl chloride is used to protect hydroxyl group. Under the condition of V(pyridine)/V(CHCl3)=1/1, ethanesulfonyl chloride3.0equivalent of stuff, we get the reaction finished within24hours without byproducts and the yield is91.8%.9,11C-C double bond product is obtained in the system of anhydrous formyl acid and anhydrous formyl sodium with small ratio of byproduct and the yield is more than63.8%. Dibromantin oxidates furan ring into cis-double bond product and trans-one. It is nice to find out the cis-one can turn into the trans-one moderately with no side reaction in room temperature and the crude yield is more than84%. Ozone oxides the trans-one into acid form with both energy conservation and environmental protection. The continuous reaction yield is63%. Good stir to make the two-phase fully mixed is the key point to get9,11double bond epoxidized and the yield after recrystallization is more than70%.