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Collective Synthesis and Biological Evaluation of Tryptophan‐Based Dimeric Diketopiperazine Alkaloids
Author(s) -
Tadano Shinji,
Sugimachi Yukihiro,
Sumimoto Michinori,
Tsukamoto Sachiko,
Ishikawa Hayato
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201503417
Subject(s) - tryptophan , chemistry , biomimetic synthesis , alkaloid , stereochemistry , natural product , combinatorial chemistry , amino acid , biochemistry
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 naseseazine B 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.