Abstract
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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This research was supported by the Sookmyung Women’s University Research Grants 2012.
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Lee, S.Y., Jung, J.W., Kim, TH. et al. Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine. Arch. Pharm. Res. 38, 2131–2136 (2015). https://doi.org/10.1007/s12272-015-0641-4
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DOI: https://doi.org/10.1007/s12272-015-0641-4