Synthesis of (Z)-4-hydroxytamoxifen and (Z)-2-[4-[1-(p-hydroxyphenyl)-2-phenyl]-1butenyl]phenoxyacetic acid.
The synthesis of (Z)-4-hydroxytamoxifen and (Z)-2-[4-[1-(p-hydroxyphenyl)-2-phenyl]-1-butenyl]phenoxyacetic acid was accomplished using a McMurry reaction as the key step. The perfluorotolyl derivatives of the McMurry products enabled the separation of the minor undesirable geometrical isomer. The methodology proceeds without E,Z isomerization, employs a very mild final debenzylation step compatible with a large array of functional groups, and can be applied to the generation of a variety of 4-hydroxytamoxifen analogues.
Detsi
Anastasia
A
Institute of Organic and Pharmaceutical Chemistry, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, 11635 Athens, Greece.
Koufaki
Maria
M
Calogeropoulou
Theodora
T
D000085:Acetates / Q000138:chemical synthesis*; D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010642:Phenoxyacetates; D013237:Stereoisomerism; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
C469721:2-(4-(1-(p-hydroxyphenyl)-2-phenyl)-1-butenyl)phenoxyacetic acid; D000085:Acetates; D010642:Phenoxyacetates; D013629:Tamoxifen; C016601:afimoxifene