title: Enantioselective total synthesis of the highly selective sphingosine-1-receptor VPC01091 by the Heck desymmetrization of a non-activated cyclopentene-fused spiro-pyrrolidinone.
abstract: A novel, efficient and enantioselective Heck-Matsuda desymmetrization of non-activated cyclopentene-fused spiro-pyrrolidinones was developed. The reaction provided the Heck products in good to excellent yields and selectivities and tolerated a variety of functional groups in arenediazonium tetrafluoroborates (12 examples) with respect to its electronics and substitution patterns. This methodology was successfully applied in the concise enantioselective total synthesis of VPC01091 (2b), a drug candidate for the treatment of multiple sclerosis.
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan and Institute of Chemistry, State University of Campinas, Josue de Castro St., Campinas, 13083-970, Brazil. roque@iqm.unicamp.br.
authors.forename: Ismat Ullah
authors.initials: IU
authors.lastname: Khan
authors.affiliation: Institute of Chemistry, State University of Campinas, Josue de Castro St., Campinas, 13083-970, Brazil. roque@iqm.unicamp.br.
authors.forename: Shivashankar
authors.initials: S
authors.lastname: Kattela
authors.affiliation: Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Abbas
authors.initials: A
authors.lastname: Hassan
authors.affiliation: Institute of Chemistry, State University of Campinas, Josue de Castro St., Campinas, 13083-970, Brazil. roque@iqm.unicamp.br.
authors.forename: Carlos Roque Duarte
authors.identifier: http://orcid.org/0000-0001-5564-6675
authors.initials: CR
authors.lastname: Correia
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D011760:Pyrrolidinones / Q000737:chemistry*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D013141:Spiro Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D003517:Cyclopentanes; D011760:Pyrrolidinones; D049349:Receptors, Lysosphingolipid; D013141:Spiro Compounds; C579735:rac-((1R*,3S*)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol hydrochloride