Huang Yaodong, Pettus Thomas R R
Department of Chemistry and Biochemistry, University of California at Santa Barbara, Santa Barbara CA 93106-9510, USA Fax +1(805)8935690; E-mail:
Synlett. 2008 May 11;9:1353-1356. doi: 10.1055/s-2008-1072750.
A kinetically controlled diastereoselective cycloaddition between a chiral enol ether and an ortho-quinone methide (o-QM) produces a chroman spiroketal motif that is found in the core of berkelic acid, a novel matrix metalloproteinase (MMP) inhibitor and potent anticancer agent. The transformation lays the groundwork for preparation of future inhibitors aimed at distinguishing among the active sites of the twenty-three known MMP. Experimental findings suggest that the stereochemistry that emerges from cycloaddition is opposite that which results from thermodynamic ketalization.
在手性烯醇醚与邻醌甲基化物（o-QM）之间进行的动力学控制的非对映选择性环加成反应生成了一个色满螺缩酮基序，该基序存在于新型基质金属蛋白酶（MMP）抑制剂和强效抗癌剂伯凯酸的核心结构中。这一转化为制备旨在区分二十三种已知MMP活性位点的未来抑制剂奠定了基础。实验结果表明，环加成反应产生的立体化学与热力学缩酮化反应产生的立体化学相反。
