Flemer Stevenson, Wurthmann Alexander, Mamai Ahmed, Madalengoitia José S
Department of Chemistry, University of Vermont, Burlington, Vermont 05405, USA.
J Org Chem. 2008 Oct 3;73(19):7593-602. doi: 10.1021/jo8012258. Epub 2008 Aug 28.
A strategy for the solid-phase diversification of PPII mimic scaffolds through guanidinylation is presented. The approach involves the synthesis N-Pmc-N'-alkyl thioureas as diversification reagents. Analogues of Fmoc-Orn(Mtt)-OH can be incorporated into a growing peptide chain on Wang resin. Side chain deprotection with 1% TFA/CH2Cl2 followed by EDCI-mediated reaction of N-Pmc-N'-alkyl thioureas with the side chain amine affords arginine analogues with modified guanidine head groups. The scope, limitations, and incidental chemistry are discussed.
本文提出了一种通过胍基化实现PPII模拟支架固相多样化的策略。该方法涉及合成N-Pmc-N'-烷基硫脲作为多样化试剂。Fmoc-Orn(Mtt)-OH的类似物可被引入到Wang树脂上不断增长的肽链中。用1% TFA/CH2Cl2进行侧链脱保护，然后N-Pmc-N'-烷基硫脲与侧链胺在EDCI介导下反应，得到具有修饰胍基头部基团的精氨酸类似物。讨论了该方法的适用范围、局限性和附带的化学反应。
