Kireev Artem S, Nadein Oleg N, Agustin Vincent J, Bush Nancy E, Evidente Antonio, Manpadi Madhuri, Ogasawara Marcia A, Rastogi Shiva K, Rogelj Snezna, Shors Scott T, Kornienko Alexander
Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801, USA.
J Org Chem. 2006 Jul 21;71(15):5694-707. doi: 10.1021/jo0607562.
Pancratistatin is a potent anticancer natural product, whose clinical evaluation is hampered by the limited natural abundance and the stereochemically complex structure undermining practical chemical preparation. Fifteen aromatic analogues of conduritol F, l-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereocenters have been synthesized and evaluated for anticancer activity. These compounds serve as truncated pancratistatin analogues lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochemistry. The lack of activity of these compounds provides further insight into pancratistatin's minimum structural requirements for cytotoxicity, particularly the criticality of the intact phenanthridone skeleton. Significantly, these series provide rare examples of simple aromatic conduritol and inositol analogues and, therefore, this study expands the chemistry and biology of these important classes of compounds.
泛喹酮是一种有效的抗癌天然产物，其临床评估因天然丰度有限以及立体化学复杂的结构阻碍了实际化学制备而受到影响。已合成了十五种拥有泛喹酮六个立体中心中的四个的conduritol F、l-手性肌醇和二氢conduritol F的芳香类似物，并对其抗癌活性进行了评估。这些化合物作为缺少内酰胺环B但保留具有正确立体化学的关键C10a-C10b键的截短泛喹酮类似物。这些化合物缺乏活性，这为泛喹酮细胞毒性的最低结构要求提供了进一步的见解，特别是完整菲啶酮骨架的关键性。值得注意的是，这些系列提供了简单芳香conduritol和肌醇类似物的罕见例子，因此，本研究扩展了这些重要化合物类别的化学和生物学。
