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KMID : 0043320150380122131
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Archives of Pharmacal Research
2015 Volume.38 No. 12 p.2131 ~ p.2136
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Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine
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Lee Sun-Young
Jung Jung-Wha
Kim Tae-Hyun
Kim Hee-Doo
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Abstract
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The first asymmetric synthesis of (R,R)-clemastine (1) has been accomplished by the coupling of (R)-tertiary alcohol 2 and (R)-chloroethylpyrrolidine 3 via O-alkylation. (R)-Tertiary alcohol 2 was synthesized by stereoselective alkylation of chiral α-benzyloxy ketone with Grignard reagent via chelation-controlled 1,4-asymmetric induction. In the reaction, chiral benzyl group acts as a chiral auxiliary as well as a protecting group. (R)-Chloroethylpyrrolidine 3 was prepared by asymmetric transformation starting with l-homoserine lactone, in which racemization-minimized N-allylation and ring-closing metathesis were involved as key steps.
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KEYWORD
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(R, R)-Clemastine, H1 receptor antagonist, Asymmetric synthesis, Asymmetric transformation
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