Song Zhiguo J, King Anthony O, Waters Marjorie S, Lang Fengrui, Zewge Daniel, Bio Matthew, Leazer Johnnie L, Javadi Gary, Kassim Amude, Tschaen David M, Reamer Robert A, Rosner Thorsten, Chilenski Jennifer R, Mathre David J, Volante R P, Tillyer Richard
Department of Process Research, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5776-81. doi: 10.1073/pnas.0307415101. Epub 2004 Apr 12.
An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.
报道了一种具有二氢苯并噻吩核心结构且带有两个手性中心的选择性雌激素受体调节剂（SERM）的高效不对称合成方法。手性中心是通过前所未有的手性亚砜导向的一步将α,β-不饱和亚砜立体定向还原为饱和硫化物而构建的。报道了阐明该还原反应机理的研究。使用高效的铜（I）介导的醚形成反应来安装醚侧链，并开发了选择性脱苄基条件以去除酚上的苄基保护基团。
