Institut de Science et Ingénierie Supramoléculaires (ISIS-UMR 7006), Université de Strasbourg-CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France.
Chemistry. 2009 Nov 2;15(43):11490-7. doi: 10.1002/chem.200901373.
The resorcylic acid lactones (RAL) are endowed with diverse biological activity ranging from transcription factor modulators (zearalenone and zearalenol) to HSP90 inhibitors (radicicol and pochonin D) and reversible (aigialomycin D) as well as irreversible kinase inhibitors (hypothemycin and other RAL containing a cis-enone). Our interest in broadening the diversity of this family beyond naturally occurring diversity has led us to seek a general approach that could be used to address the entire spectrum of functionalities present within this family. Herein, we present our efforts on accessing macrocycles bearing an alkane, alkene, or epoxide at the benzylic position from a common benzylic sulfide intermediate to access L-783277, LL-Z1640-2, and hypothemycin.
雷锁辛内酯（RAL）具有多种生物学活性，包括转录因子调节剂（玉米赤霉烯酮和玉米赤霉烯醇）、HSP90 抑制剂（拉替洛尔和波考诺因 D）、可逆（阿吉霉素 D）以及不可逆激酶抑制剂（hypothemycin 和其他含有顺式烯酮的 RAL）。我们对扩大这个家族的多样性的兴趣超越了自然存在的多样性，这促使我们寻求一种通用的方法，可以用来解决这个家族中存在的整个功能谱。在这里，我们介绍了我们从常见的苄基硫化物中间体中获得苄位带有烷烃、烯烃或环氧化物的大环的努力，以获得 L-783277、LL-Z1640-2 和 hypothemycin。
