title: Asymmetric synthesis of H1 receptor antagonist (R,R)-clemastine.
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.
authors.affiliation: College of Pharmacy, Sookmyung Women's University, 53-12, Chungpa-Dong, Yongsan-Ku, Seoul, 140-742, Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Sookmyung Women's University, 53-12, Chungpa-Dong, Yongsan-Ku, Seoul, 140-742, Korea.
authors.forename: Jung Wha
authors.initials: JW
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Sookmyung Women's University, 53-12, Chungpa-Dong, Yongsan-Ku, Seoul, 140-742, Korea.
authors.forename: Tae-Hyun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Sookmyung Women's University, 53-12, Chungpa-Dong, Yongsan-Ku, Seoul, 140-742, Korea. hdkim@sm.ac.kr.
authors.forename: Hee-Doo
authors.initials: HD
authors.lastname: Kim
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002974:Clemastine / Q000138:chemical synthesis*; D006634:Histamine H1 Antagonists / Q000138:chemical synthesis*; D011969:Receptors, Histamine H1 / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D002974:Clemastine
keywords: (R,R)-Clemastine; Asymmetric synthesis; Asymmetric transformation; H1 receptor antagonist