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Enantioselective resolution of Rac ‐terbutaline and evaluation of optically pure R ‐terbutaline hydrochloride as an efficient anti‐asthmatic drug
Author(s) -
Beng Huimin,
Zhang Hao,
Jayachandra R.,
Li Junxiao,
Wu Jie,
Tan Wen
Publication year - 2018
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.22846
Subject(s) - terbutaline , chemistry , enantiomer , hydrochloride , enantioselective synthesis , pharmacology , bronchodilator , stereochemistry , asthma , organic chemistry , medicine , catalysis
Terbutaline is a β 2 ‐adrenoceptor agonist for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Among the two isomers of terbutaline (TBT 2), R ‐isomer was found to be the potent enantiomer in generating therapeutic effect, while S ‐isomer has been reported to show side effects. In this study, R ‐terbutaline hydrochloride ( R ‐TBH 6) was synthesized through chiral resolution from the racemic terbutaline sulfate ( rac ‐TBS 1) with 99.9% enantiomeric excess (ee) in good overall yield (53.6%). Further, R ‐TBH 6 nebulized solution was prepared in half dosage of Bricanyl®, which is a marketed product of racemic terbutaline and evaluated in vitro aerosol performance and in vivo anti‐asthmatic effect on guinea pigs via . pulmonary delivery. From the investigation, it is evident that R ‐TBH 6 nebulized solution of half dosage performed similar fine aerosol characteristics and anti‐asthmatic effect with Bricanyl®.