| This thesis consists of two parts. The first part is the study of clindamycin phosphate抯 new synthesis route. (1) On a basic of systematic investigation of reference, the synthetic method from lincomycin by chlorizating and phosphorating,was studied systematically. The reaction is as following CH, CH, CM, H N H HO-C-H H N H H桟桟l CONI-l-CH .HCI DMF-POCI, CONHCH 旽CI .C,H,OH HC3H1 C,H4CI,, C2H,OH o H H ~ C,H7 H H H H OH H H OH 3 SCd, H OH HOH CH, CM, CH, CM, I I H H N H H桟桟l (CH,)2C0 C H (I)POC1,, r4ji~ k~N... H3 H + ~C,H7H/ CONH-CH (2) H,O 慼桰? ~yH~C-Ci H H ~OHHjI H SCM, H~扴C~ H OH H 0 HO-P=O Ott During the chlorizating, a new one-pot method was used. The treatment method for the salt formation was unproved greatly. In the reaction, A new kind of complex reagent A found by us made the protecting and phosphorating reaction being conducting in the same system. The chromatographic separation and crystalling condition of the product were also explored and improved. The thermal stability for product was studied. The total yield of the new route was about 70%. This route has some advantages such as material easily available, mild reaction condition, convenient operation and high yield, etc. It has been applied to industrial production. (2) Effection on crystal category of the clindamycin phosphate by using different crystallizing conditions was studied for the first time. (3) 31P-NIvIR spectra were used as an efficient checking method in the protecting reaction and hydrolysation firstly. The quantitative relationship for the various intermediates in the reaction was explained. This study was instructive 2 to the preparation of clindamycin phosphate and have some creative meamng. The second part is synthesis of p-hydroxyphenyl ethanol, that is an important pharmaceutical mediate, was synthesized by using p- hydroxyphenyl ethyl methyl ester as material. The optimum condition was explored. This new route has the advantages of material easily available and recyclable, mild reaction condition, etc. |
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