Synthesis of boroxifen, a nido-carborane analogue of tamoxifen.
A nido-carborane analogue of tamoxifen, the widely employed breast cancer therapy agent, was prepared as an archetype of a potential new class of antiestrogen and boron neutron capture therapy agent in which the carborane is incorporated within the framework of the parent compound. The carborane was introduced through the reaction of 6,9-bis(acetonitrile)decaborane with a unique and highly conjugated ene-yne, which was prepared stereoselectively. NMR spectroscopy and a crystal structure of a key intermediate, the carborane analogue of chloro-tamoxifen, demonstrated the structural similarities between the tamoxifen carboranes and their corresponding phenyl analogues.
Valliant
John F
JF
Department of Chemistry and The Medical Physics Unit, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada, L8S 4M1. valliant@mcmaster.ca
Schaffer
Paul
P
Stephenson
Karin A
KA
Britten
James F
JF
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry*; D001896:Boron Compounds / Q000737:chemistry; D016754:Boron Neutron Capture Therapy; D002384:Catalysis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D020847:Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry
D000970:Antineoplastic Agents; D001896:Boron Compounds; D020847:Estrogen Receptor Modulators; C449941:boroxifen; D013629:Tamoxifen