(Z)-1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane: the synthesis and enantiomeric separation of an antitumor agent.
(Z)-1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyc lopropane (5), a potential antitumor agent designed to treat breast cancer, was prepared in three steps. A stereospecific palladium-catalyzed cross coupling reaction which provided the intermediate (Z)-triaryl alkene 4 was a crucial step in the synthesis. Makosza phase transfer reaction on 4 gave the enantiomeric (Z)-dichlorocyclopropane derivatives 5 which were resolved by semipreparative HPLC on a chiral stationary phase consisting of amylose tris-3,5-dimethylphenyl carbamate coated on silica gel.
Medicinal Chemistry/Pharmacodynamics Section, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
K L
KL
Meyer
R A
RA
Magarian
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D010165:Palladium / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D003521:Cyclopropanes; C088187:1,1-dichloro-2-(4-benzyloxyphenyl)-2,3-bis(4-methoxyphenyl)cyclopropane; D010165:Palladium