Conformationally constrained substance P analogues: the total synthesis of a constrained peptidomimetic for the Phe7-Phe8 region.
Conformationally constrained substance P analogues: the total synthesis of a constrained peptidomimetic for the Phe7-Phe8 region.
复制标题
构象受限的 P 物质类似物：Phe7-Phe8 区域受限的拟肽的全合成。
DOI：
10.1021/jo991649t
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Moeller,KD
中科院分区：
文献类型：
--
作者：
Tong,Y;Fobian,YM;Wu,M;Boyd,ND;Moeller,KD
A lactam-based peptidomimetic for the Phe7-Phe8region of substance P has been synthesized. The synthesis used an anodic amide oxidation to selectively functionalize the C5-position of a 3-phenylproline derivative. The resulting proline derivative was coupled to a Cbz-protected phenylalanine, and an intramolecular reductive amination strategy used to convert the coupled material into a bicyclic piperazinone ring skeleton. The net result was a dipeptide building block that imbedded one of two proposed receptor bound conformations for the Phe7-Phe8region of substance P into a bicyclic ring skeleton. The building block was then converted into a constrained substance P analogue with the use of solid-phase peptide synthesis. A similar intramolecular reductive amination strategy was used to synthesize a substance P analogue having only Phe7constrained, and the original 3-phenylproline was converted into a substance P analogue having only Phe8constrained. All of the analogues were examined for their ability to displace substance P from its NK-1 receptor.
