Collective Synthesis and Biological Evaluation of Tryptophan-Based Dimeric Diketopiperazine Alkaloids
Collective Synthesis and Biological Evaluation of Tryptophan-Based Dimeric Diketopiperazine Alkaloids
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DOI：
10.1002/chem.201503417
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发表时间：
2016-01-22
影响因子：
4.3
通讯作者：
Ishikawa, Hayato
中科院分区：
文献类型：
--
作者：
Tadano, Shinji;Sugimachi, Yukihiro;Ishikawa, Hayato
基于色氨酸衍生物在酸性水溶液中独特的生物激发二聚化反应和二酮哌嗪环的一锅法，详细介绍了WIN 64821、eurocristatine、15,15′-双-epi-eurocristatine、diryptophenaline、diryptoleucine A、WIN 64745、cristatumin C、asperdimin、naseseazine A和naseseazineB的简明两锅法合成。这些生物碱的总收率从10%到27%不等。另外，采用三次一锅法合成了1′-（2-苯基乙烯）-二苯苯酚。本文的研究提供了合成的抑制巨噬细胞中泛素特异性蛋白酶7 （USP7）活性和泡沫细胞形成的天然产物。新上市的以色氨酸为基础的二聚二酮哌嗪类生物碱的生物学评价发现15,15′-双表-eurocristatine、1′-（2-苯基乙烯）- diryptophenaline和WIN 64745为候选新药。
A concise two one-pot synthesis of WIN 64821, eurocristatine, 15,15'-bis-epi-eurocristatine, ditryptophenaline, ditryptoleucine A, WIN 64745, cristatumin C, asperdimin, naseseazine A, and naseseazineB is detailed, based on a unique bioinspired dimerization reaction of tryptophan derivatives in aqueous acidic solution and a one-pot procedure for the construction of diketopiperazine rings. Total yields of these alkaloid syntheses were from 10 up to 27%. In addition, 1'-(2-phenylethylene)-ditryptophenaline was synthesized by using three one-pot operations. The studies detailed herein provided synthesized natural products for inhibitory activities of ubiquitin-specific protease 7 (USP7) and foam cell formation in macrophages. The newly listed biological evaluation for tryptophan-based dimeric diketopiperazine alkaloids discovered 15,15'-bis-epi-eurocristatine, 1'-(2-phenylethylene)-ditryptophenaline, and WIN 64745 as new drug candidates.