title: A formal synthesis of ezetimibe via cycloaddition/rearrangement cascade reaction.
abstract: A formal synthesis of a powerful cholesterol inhibitor, ezetymibe 1, is described. The crucial step of the synthesis is based on Cu(I)-mediated Kinugasa cycloaddition/rearrangement cascade reaction between terminal acetylene derived from acetonide of L-glyceraldehyde and suitable C,N-diarylnitrone. The adduct with (3R,4S) configuration at the azetidinone ring, obtained with high stereoselectivity, was subsequently subjected to deprotection of the diol side chain followed by glycolic cleavage and base-induced isomerization at the C3 carbon atom to afford the (3S,4S) aldehyde, which has been already transformed into ezetimibe by the Schering-Plough group.
authors: Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland.
authors: Michał
authors: M
authors: Michalak
authors: Maciej
authors: M
authors: Stodulski
authors: Sebastian
authors: S
authors: Stecko
authors: Adam
authors: A
authors: Mames
authors: Irma
authors: I
authors: Panfil
authors: Magdalena
authors: M
authors: Soluch
authors: Bartłomiej
authors: B
authors: Furman
authors: Marek
authors: M
authors: Chmielewski
mesh_terms: D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001384:Azetidines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D000069438:Ezetimibe; D005985:Glyceraldehyde / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D005985:Glyceraldehyde; D000069438:Ezetimibe