title: A convenient synthesis of (Z)-4-hydroxy-N-desmethyltamoxifen (endoxifen).
abstract: A mixture of the (Z)- and (E)-isomers of 4-hydroxy-N-desmethyltamoxifen was conveniently prepared in four steps. These geometrical isomers were then neatly separated by semi-preparative Reverse Phase High Performance Liquid Chromatography (RP-HPLC) using specified conditions. Additionally, the isolated E-isomer could be equilibrated in aqueous strong acid in acetonitrile or trifluoroacetic acid/dichloromethane to give a clean 1:1 mixture of Z/E isomers that was re-subjected to HPLC separation. In this way, most of the undesired (E)-isomer could be readily converted to the desired (Z)-isomer providing quick access to over 200mg quantities of pure endoxifen (Z-isomer), a potent antiestrogenic metabolite of tamoxifen traditionally used in breast cancer treatment.
authors.affiliation: Chemical Synthesis Core Facility, Mayo Clinic Jacksonville, FL 32246, USA. fauq.abdul@mayo.edu
authors.forename: Abdul H
authors.initials: AH
authors.lastname: Fauq
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Maharvi
authors.forename: Dola
authors.initials: D
authors.lastname: Sinha
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D006801:Humans; D013237:Stereoisomerism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D013629:Tamoxifen; C055492:4-hydroxy-N-desmethyltamoxifen