Reznik Samuel K, Leighton James L
Department of Chemistry, Columbia University, 3000 Broadway, New York, New York, 10027, USA.
Chem Sci. 2013 Apr 1;4(4):1497-1501. doi: 10.1039/C3SC22186E.
An efficient, step-economical, and scalable synthesis of a diene-bearing AB spiroketal fragment of spongistatin 1, and a demonstration of its efficient coupling to an aldehyde derived from silylformylation of a homopropargyl alcohol to produce the entire complex C(13)-C(17) linker region are described. The scalability of the synthesis of the AB spiroketal fragment was demonstrated by the preparation of 34.5 grams by one chemist in ~60 workdays, and more than 40 grams overall. With this material in hand and having established a method for its efficient coupling to the CD fragment, we have set the stage for the rapid synthesis and evaluation of a series of analogs of the CD spiroketal.
描述了一种高效、步骤经济且可扩展的海绵他汀1含二烯AB螺缩酮片段的合成方法,以及将其与由高炔丙醇硅基甲酰化衍生的醛进行有效偶联以生成整个复杂的C(13)-C(17)连接区域的过程。一位化学家在约60个工作日内制备了34.5克AB螺缩酮片段,总体超过40克,证明了该片段合成的可扩展性。有了这种材料并建立了将其与CD片段有效偶联的方法后,我们为快速合成和评估一系列CD螺缩酮类似物奠定了基础。