Solid-phase synthesis of cyclic peptides containing p-(tri-n-butyl-stannyl)-phenylalanine residue

p-(トリ-n-ブチルスタニル)-フェニルアラニン残基を含む環状ペプチドの固相合成

津久井 匠隆; 山田 圭一*; 渡邉 茂樹; 花岡 宏史*; 奥 浩之*; 遠藤 啓吾*; 石岡 典子; 松尾 一郎*

Tsukui, Narutaka; Yamada, Keiichi*; Watanabe, Shigeki; Hanaoka, Hirofumi*; Oku, Hiroyuki*; Endo, Keigo*; Ishioka, Noriko; Matsuo, Ichiro*

p-(tri-n-butyl-stannyl)-phenylalanine (Phe(p-BuSn)) is an useful building blocks for synthesizing radiolabeled pharmaceutics. To best of our knowledge, there are few studies of the synthesis of Phe(p-BuSn)-containing peptides. In this study, we report solid-phase synthesis of cyclic peptides containing Phe(p-BuSn) residue, cyclo(Phe(p-BuSn)-Leu-MeLeu-Val-Leu) (I). Boc-Phe(p-BuSn)-OH was synthesized from Boc-Phe(p-I)-OMe by treatment with bis(tri-n-butyl)tin and Pd(0) catalyst followed by saponification. The linear peptide containing Phe(p-BuSn) residue was assembled on Kaiser-oxime resin. On-resin macrocyclization of the linear peptide, however, did not afford the cyclic peptide I. Cross coupling of cyclic peptide containing Phe(p-I) residue, cyclo(Phe(p-I)-Leu-MeLeu-Val-Leu) with bis(tri-n-butyl)tin and Pd(0) catalyst gave the desired peptide, which was confirmed by ESI-MS. In this presentation, we will report the Fmoc-SPPS of the peptide I.