Asymmetric Synthesis Of Leukotriene Receptor Antagonist Montelukast

Montelukast（1）,a selective oral leukotriene receptor antagonist,was developed by Merck Inc.. It was first launched as Singular^?in England in 1997.1 was indicated for the prophylaxis and chronic treatment of asthma in adults and pediatric patients 2 years of age and older,and also for the relief of symptoms of allergic rhinitis（seasonal allergic rhinitis,SAR）.The pathogeny and pathogenesis of asthma were summarized in this thesis.Here also introduced the commonly used antiasthmatic medicines,and reviewed the progress of leukotriene receptor antagonists developed in recent years.A novel route for the asymmetric synthesis of 1 was designed and studied in this thesis.1 was successfully prepared from 1-bromo-2-（bromomethyl）benzene and 3-bromobenzaldehvde in a 16-step convergent sequence.The structure of the target compound was determined by 1H NMR and ESI-MS.This new route has not yet been reported in literature.The selective reduction of 39 was a key step in the synthesis.After extensively uming,it could be selectively reduced to chiral compound 40 via CBS reduction by KBH₄/SnCI₂.