特殊植物生物碱可毒杀癌细胞
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Bioorganic & Medicinal Chemistry，doi:10.1016/j.bmc.2008.04.032 ，Chung-Ren Su，Tian-Shung Wu

Total synthesis of phenanthroindolizidine alkaloids (±)-antofine, (±)-deoxypergularinine, and their dehydro congeners and evaluation of their cytotoxic activity

Chung-Ren Sua, Amooru G. Damua, Po-Cheng Chiangb, Kenneth F. Bastowb, Susan L. Morris-Natschkeb, Kuo-Hsiung Leeb and Tian-Shung Wua, ,

aDepartment of Chemistry, National Cheng Kung University, Tainan 701, Taiwan, ROC
bNatural Products Research Laboratories, School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States

Due to their limited natural abundance and significant biochemical effects, we synthesized the alkaloids (±)-antofine (1a), (±)-deoxypergularinine (1b), and their dehydro congeners (2 and 3) starting from the corresponding phenanthrene-9-carboxaldehydes. We also evaluated their in vitro cytotoxic activity. Compounds 1a and 1b showed significant potency against various human tumor cell lines, including a drug-resistant variant, with EC50 values ranging from 0.16 to 16 ng/mL. Structure–activity correlations of these alkaloids and some of their synthetic intermediates were also ascertained. The non-planar structure between the two major moieties, phenanthrene and indolizidine, plays a crucial role in the cytotoxic activity of phenanthroindolizidines. Increasing the planarity and rigidity of the indolizidine moiety significantly reduced potency. A methoxy group at the 2-position (1a) was more favorable for cytotoxic activity than a hydrogen atom