ABSTRACT
Objective To improve the synthetic procedure of the HIV integrase inhibitor raltegravir. Methods With 2-ami-no-2-methyl-propionitrile hydrochloride as starting material,the target compound raltegravir was synthesized through amino protection by benzyl chloroformate ,amidoxime formation,cyclization induced by michael addition&Claisen rearrangement,N-methylation,N-acylation,hydroxyl protection by trimethylacetyl chloride,hydrogenolysis by the system of Pd/C and formic acid,amidation with the 5-methyl-1,3,4-oxadiazol-formyl chloride,and immediate hydrolysis without more purification. Results The chemical structure of raltegravir and the intermediates were characterized by 1H NMR,13C NMR and MS. The overall yield was about 19.45%. Conclusion Compared with the preceding process,the developed route is easy to operate,safe and suitable for industrialized production in accor-dance with the quality standard of active pharmaceutical ingredient(API).
ABSTRACT
Objective To establish a HPLC method for determining notoginsenoside R1,and ginsenosides Rg1 and Rb1 in Xixian Tongshuan pills. Methods C18 column was adopted with acetonitrile as mobile phase A,water as mobile phase B,gradient elution. The flow rate was 1.0 ml/min,column temperature was 35℃and detection wavelength was 203 nm. Results The linear range of notoginsenoside R1,and ginsenosides Rg1 and Rb1 was 0.412-1.855μg(r=0.9994),1.903-8.563μg(r=0.9994),and 1.822-8.201μg(r=1.0000),respectively. The total average recovery rate of notoginsenoside R1,and ginsenosides Rg1 and Rb1 was 98.48%, 97.33%and 97.29%with RSD of 1.58%,1.13%and 1.08%,respectively. Conclusion The method is reliable,accurate,and can be used for the quality control of the preparation.