Wang Xiaodong J, Hart Scott A, Xu Bailing, Mason Matthew D, Goodell John R, Etzkorn Felicia A
Department of Chemistry, MC 0212, Virginia Tech, Blacksburg, Virginia 24061, USA.
J Org Chem. 2003 Mar 21;68(6):2343-9. doi: 10.1021/jo026663b.
Two new amide isosteres of Ser-cis-Pro and Ser-trans-Pro dipeptides were designed and stereoselectively synthesized to be incorporated into potential inhibitors of the phosphorylation-dependent peptidylprolyl isomerase Pin1, an essential regulator of the cell cycle. The cis mimic, the (Z)-alkene isomer, was formed through the use of a Still-Wittig [2,3]-sigmatropic rearrangement, while the trans mimic, the (E)-alkene, was synthesized through the use of an Ireland-Claisen [3,3]-sigmatropic rearrangement. Starting from N-Boc-Ser(OBn)-N(OMe)Me, both mimics were synthesized in Boc-protected form suitable for peptide synthesis with an overall yield of 20% in 10 steps for the cis mimic and 13% in eight steps for the trans mimic.
设计并立体选择性合成了两种新型的Ser-顺式-Pro和Ser-反式-Pro二肽的酰胺生物电子等排体，用于构建细胞周期关键调节因子——磷酸化依赖性肽脯氨酰顺反异构酶Pin1的潜在抑制剂。顺式模拟物，即(Z)-烯烃异构体，通过Still-Wittig [2,3] - 迁移重排反应形成；而反式模拟物，即(E)-烯烃，则通过Ireland-Claisen [3,3] - 迁移重排反应合成。以N-Boc-Ser(OBn)-N(OMe)Me为起始原料，两种模拟物均以适合肽合成的Boc保护形式合成，顺式模拟物经10步反应，总产率为20%；反式模拟物经8步反应，总产率为13%。
