Mothes Céline, Lavielle Solange, Karoyan Philippe
UPMC Univ Paris 06, UMR 7613 and FR2769, Synthèse, Structure et Fonction de Molécules Bioactives, Fédération de Chimie Moléculaire, UPMC, 4, Place Jussieu, 75252, Paris Cedex 05, France.
J Org Chem. 2008 Sep 5;73(17):6706-10. doi: 10.1021/jo801006a. Epub 2008 Jul 26.
Proline chimeras are useful tools for medicinal chemistry and/or biological applications. The asymmetric synthesis of cis-3-substituted prolines can be easily achieved via amino-zinc-ene-enolate cyclization followed by transmetalation of the cyclic zinc intermediate for further functionalization. Syntheses of prolino-homotryptophane derivatives were achieved through Negishi cross-coupling of the zinc intermediate with indole rings. The use of Pd catalyst derived from Fu's [(t-Bu3)PH]-BF4 was required to avoid the undesired beta-hydride elimination. Optically pure and orthogonally protected compounds were obtained readily usable for peptide synthesis.
脯氨酸嵌合体是药物化学和/或生物学应用的有用工具。顺式-3-取代脯氨酸的不对称合成可通过氨基锌-烯醇化物环化，然后将环状锌中间体进行金属转移以进一步官能化来轻松实现。脯氨-高色氨酸衍生物的合成是通过锌中间体与吲哚环的根岸交叉偶联实现的。需要使用源自傅氏[(t-Bu3)PH]-BF4的钯催化剂来避免不希望的β-氢化物消除。可轻松获得光学纯且具有正交保护的化合物，可用于肽合成。
