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Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine

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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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Fig. 1
Scheme 1
Scheme 2
Fig. 2

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Acknowledgments

This research was supported by the Sookmyung Women’s University Research Grants 2012.

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Correspondence to Hee-Doo Kim.

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All authors declare that there is no conflict of interest with any financial, personal or other relationships with other people or organizations that could inappropriately influence or be perceived to influence this study.

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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

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