Custar Daniel W, Zabawa Thomas P, Hines John, Crews Craig M, Scheidt Karl A
Department of Chemistry, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208, USA.
J Am Chem Soc. 2009 Sep 2;131(34):12406-14. doi: 10.1021/ja904604x.
The total synthesis and biological evaluation of neopeltolide and analogs are reported. The key bond-forming step utilizes a Lewis acid-catalyzed intramolecular macrocyclization that installs the tetrahydropyran ring and macrocycle simultaneously. Independent of each other, neither the macrolide nor the oxazole side chain substituents of neopeltolide can inhibit the growth of cancer cell lines. The biological data of the analogs indicate that alterations to either the ester side chain or the stereochemistry of the macrolide result in a loss of biological activity.
报道了新佩托利德及其类似物的全合成和生物学评价。关键的成键步骤采用了路易斯酸催化的分子内大环化反应,该反应同时构建了四氢吡喃环和大环。新佩托利德的大环内酯和恶唑侧链取代基彼此独立,均不能抑制癌细胞系的生长。类似物的生物学数据表明,大环内酯的酯侧链或立体化学发生改变都会导致生物活性丧失。