Effect of acids on isomer formation of tricyclic antidepresant drugs

Doxepin, and Dothiepin belonging to tricyclic antidepressants exists as a mixture of E & Z isomers; whereas the activity of Doxepin and Dothiepin is attributed to there E-isomers. Therefore in the present study, doxepin and dothiepin have been synthesized and separation of E and Z isomers was achieved by HPLC to know the percentage of E isomer in doxepin and Dothiepin. Since the activity of doxepin and dothipin is dependent on the E isomer, effects of various acids in the formation of E isomer is dealt with. Doxepin and dothiepin synthesis, in the penultimate step involves the dehydration of (11RS)-11[3-(dimethylamino)propyl]-6,11- dihydrodibenzo[b,e]oxepin-11-ol and (11RS)-11[3-(dimethylamino)propyl]-6,11-dihydrodibenzo[b,e]thiepin-11-ol by acid leading to formation E and Z isomers. In this study, attempts have been made to study the effects of various acids such as oxalic acid, maleic acid, phosphoric acid, p-toluyl sulphonic acid, Indian resin-220 and tartaric acid in improving the formation E isomer and reduction in the formation of Z-isomer. E -isomer formation was found to be optimum with the use of tartaric acid, Indian resin-220 and p-toluyl sulphonic acid.

Autorentext

Mr. Amit Kumar Jain completed his Master of Pharmacy In Pharmaceutical chemistry in 2008 and pursuing Doctor of Philosophy in Pharmaceutical Science from Oriental University, Indore, Mr. Jain having 14 year of experience in Education and Research, published 15 research papers in national and International Journals.