Leighty Matthew W, Georg Gunda I
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Lawrence, Kansas 66045 and Department of Medicinal Chemistry and The Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware Street SE, Minneapolis, Minnesota 55414.
ACS Med Chem Lett. 2011 Apr 14;2(4):313-315. doi: 10.1021/ml1003074.
Both enantiomers of boehmeriasin A were synthesized in seven steps each, using a chiral pool approach. Key steps in the synthesis are a one-flask, two-step protocol to generate the quinolizine core and a C-H functionalization reaction between tetrahydroquinolizinones and an aryltrifluoroborate. The natural product (R)-boehmeriasin A demonstrated potent cytotoxicity against several cancer cell lines, whereas the unnatural (+)-(S)-isomer was significantly less potent.
采用手性源方法，以七步反应分别合成了波美草素A的两种对映体。合成的关键步骤包括：通过单瓶两步法生成喹嗪核心，以及四氢喹嗪酮与芳基三氟硼酸盐之间的C-H官能化反应。天然产物(R)-波美草素A对几种癌细胞系表现出强大的细胞毒性，而非天然的(+)-(S)-异构体活性则明显较弱。
