Discovery Chemistry, ‡Chemical and Synthetic Development, and §Pharmaceutical Candidate Optimization, Research and Development, Bristol-Myers Squibb Company , P.O. Box 4000, Princeton, New Jersey 08543-4000, United States.
J Org Chem. 2016 Oct 7;81(19):9499-9506. doi: 10.1021/acs.joc.6b01965. Epub 2016 Sep 26.
A one-step synthesis of Fmoc-protected aryl/heteroaryl-substituted phenylalanines (Bip derivatives) using the nonaqueous palladium-catalyzed Suzuki-Miyaura cross-coupling (SMC) reaction of Fmoc-protected bromo- or iodophenylalanines is reported. This protocol allows for the direct formation of a variety of unnatural biaryl-containing amino acids in good to excellent yield, which can be readily used in subsequent Fmoc solid-phase peptide synthesis. The synthetic utility of this method is also demonstrated by the SMC reaction of bromophenylalanine-containing tripeptides.
本文报道了一种通过非水相钯催化的 Suzuki-Miyaura 交叉偶联（SMC）反应一步合成 Fmoc 保护的芳基/杂芳基取代苯丙氨酸（Bip 衍生物）的方法，该方法使用 Fmoc 保护的溴代或碘代苯丙氨酸。该方案允许直接形成多种非天然的含联苯氨基酸，产率良好至优秀，可在随后的 Fmoc 固相肽合成中直接使用。该方法的合成实用性还通过含溴苯丙氨酸的三肽的 SMC 反应得到了证明。
