109640-29-1Relevant academic research and scientific papers
Synthesis of Highly Stereodefined Tetrasubstituted Acyclic All-Carbon Olefins via a Syn-Elimination Approach
Lim, Ngiap-Kie,Weiss, Patrick,Li, Beryl X.,McCulley, Christina H.,Hare, Stephanie R.,Bensema, Bronwyn L.,Palazzo, Teresa A.,Tantillo, Dean J.,Zhang, Haiming,Gosselin, Francis
supporting information, p. 6212 - 6215 (2017/11/24)
An efficient synthesis of stereodefined tetrasubstituted acyclic all-carbon olefins has been developed via a bis(2,6-xylyl)phosphate formation of stereoenriched tertiary alcohols, followed by in situ syn-elimination of the corresponding phosphates under mild conditions. This chemistry tolerates a wide variety of electronically and sterically diverse substrates and generates the desired tetrasubstituted olefins in high yields and stereoselectivities (>95:5) in most cases. This stereocontrolled olefin synthesis has been applied to the synthesis of anticancer drug tamoxifen in three steps from commercially available 1,2-diphenylbutan-1-one in 97:3 stereoselectivity and 78% overall yield.
Synthesis, Conformational Considerations, and Estrogen Receptor Binding of Diastereoisomers and Enantiomers of 1-phenyl>-1,2-diphenylbutane (Dihydrotamoxifen)
McCague, Raymond,Leclercq, Guy
, p. 1761 - 1767 (2007/10/02)
As part of a study into nonisomerizable antiestrogens, the diastereoisomeric dihydrotamoxifens 7 and 8 were prepared by catalytic transfer hydrogenation of (Z)- and (E)-tamoxifen and were shown by NMR spectrometry to exist in preferred conformations with hydrogen atoms in an antiperiplanar relationship.The corresponding 4-hydroxy derivatives 9 and 10 were prepared from hydrogenated precursors of (Z)- and (E)-4-hydroxytamoxifen.The relative binding affinities (RBA) of the compounds to estrogen receptors are consistent with the assigned conformations and parallel reported data on derivatives of the nonsteroidal estrogen hexestrol.The growth-inhibitory activity against the MCF-7 human breast cancer cell line in vitro was for 10 comparable to that of 4-hydroxytamoxifen, although increasing the concentration from 10-8 to 10-6 M did not significantly improve the growth inhibition.The derivative 9 analogous to (E)-4-hydroxytamoxifen antagonized the growth-stimulating effect of added estradiol and is therefore also an antiestrogen but at low concentration (10-8 M) in the absence of estradiol, MCF-7 cell growth was stimulated, indicating an estrogenic influence.The enantiomers of the dihydrotamoxifen 8 were individually prepared from the resolved enantiomers of 2-phenylbutanoic acid, the key reaction step being a lithium-ammonia reduction of the 1-(4-methoxyphenyl)-1,2-diphenyl-1-butanol to generate the triphenylbutane.The enantiomers of 8 gave identical RBA values in cytosol.
Stereoselective Olefin Formation from the Dehydration of 1-(p-Alkoxyphenyl)-1,2-diphenylbutan-1-ols: Application to the Synthesis of Tamoxifen
McCague, Raymond
, p. 1011 - 1016 (2007/10/02)
Acid-catalysed dehydration of either diastereoisomer of a 1-(p-alkoxyphenyl)-1,2-diphenylbutan-1-ol gives mainly the Z isomer of the but-1-ene via a common carbenium ion intermediate that can be regenerated by protonation of the (Z)- or (E)-butene with fluorosulphonic acid.Highly stereoselective syn eliminations were achieved by treatment of the butan-1-ols with base and carbon disulphide but dehydrations using N,N,N-triethylammonio-N'-methoxycarbonylsulphamidate proceeded mainly via a carbenium ion.Aspects of the stereoselectivity of the reactions are discussed.The methods can be applied to give simple stereoselective syntheses of the anti-cancer drug tamoxifen.
