Synthesis Study And Quality Control Of Phacolysin

Cataract is an ophthalmic disease.There are many pathogenic factors of cataract,including ultraviolet exposure,severe eye injury,diabetes,chronic inflammation and so can cause the metabolism of crystalline protein disorders.Resulting in lens protein degeneration and turbidity,it formed a cataract.According tothe classification of cataract risk factors,the cataract is divided into radioactive cataract,senile cataract,metabolic cataract,traumatic cataract and congenital cataract.When the patient has cataract,it will feel blurred vision,and no obvious pain,and color recognition changes and glare.Currently for the treatment of cataract surgery by implantation of intraocular lens and drug treatment of two.Phacolysin,named as Sodium 5,12-dihydro-5,7,12,14-tetra-azape-ntacene-2,9-disulfonate was developed by Zeria Pharmaceutical Co.,Ltd.in Japan in 1963,and was used as a for the prevention andtreatment for senile cataracts.It can easily penetrate into lens overthe organization as a eye drops,and it also has strong affinity forsoluble protein in lens,with which it can prevent lens from getting oxidation,degenerating and becoming muddy caused by quinone substanc-es.Meanwhile it can make the denatured protein decomposedand absorbed,which helps the lens to maintain transparent,improvethe metabolism of eye tissue and prevent the development of cataract.This paper mainly studies on the synthesis and process conditions of Phacolysin.Referring to literature,the synthesis of Phacolysin consist of two parts,the firstoneisthesynthesisofanimportantintermediate5,12-dihydro-5,7,12,14-tetraazapentacenes(DHTAP),the second one is to obtain Sodium sulfonate status by sulfonating DHTAP.The synthesis route of DHTPA is composed of complicated process from many literatures.This paper improves the experimental way which has been reported before,and proposes a total synthesis route to obtain Phacolysin,which has simple operation and low cost.The improved way which has three steps used O-phenylenediamine as raw material.Firstly,2,3-dia-minophenazine (?) was ge-nerated by condensation of two O-phenylenediamine.Secondly,The Intermediate 5,12-dihydro-5,7,12,14-tetraaza pentacenes (?) was obtained by condensation of another O-phenylenediamine.Finally,to give the Phacolysin with chlorosulfonic acid under the positioning ef fect of mercury sulfate.In this route,it's easy to obtain the starting material with low cost.And reaction condition is mild.The first stepcan be reached at room temperature with the purified water as the solvent.In the second step,the improved way can avoid the using of fuming sulfuric acid as catalyzer,which can reduce emission of acid waste water and sulfur trioxide or other exhaust gas.The sulfonic acid groups can be attacked selectively under the utilization of mercury sulfate as orientating group.Phacolysin's purity was carried out by quality control,it is decolorizated by column chromatography,and recrystallization in order to obtain a relatively pure method.It's difficult to deal with the viscous reaction liquid when using sulfuric acid or fuming sulfuric acid as sulfonation reagent,but this problem can be resolved by using chlorosulfonic acid as sulfonation reagent.After reaction,the reaction liquid is poured into ice water directly.After the left chlorosulfonic acid wasquenched,chlorosulfonates can be hydrolyzed in ice water to produce sulfonated products.The chemical structure of Phacolysin and its important intermediates were confirmed by ~1H-NMR and MS.