Effect of acids on isomer formation of tricyclic antidepresant drugs. Effect of different acids on the z isomer formation of Doxepin and dothiepin

      Аннотация: 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.

Ключевые слова: Z isomer, doxepin, Dothiepin, Tricyclic Antidpressant, HPLC, NMR