- Collective synthesis and biological evaluation of tryptophan-based dimeric diketopiperazine alkaloids
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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. All in one: A concise synthesis of tryptophan-based dimeric diketopiperazine alkaloids (see scheme) is detailed based on a unique bioinspired dimerization reaction of tryptophan derivatives and a one-pot procedure for construction of diketopiperazine rings. Some of the synthetic alkaloids were discovered as new drug candidates for cancer or atherosclerosis therapy.
- Tadano, Shinji,Sugimachi, Yukihiro,Sumimoto, Michinori,Tsukamoto, Sachiko,Ishikawa, Hayato
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supporting information
p. 1277 - 1291
(2016/01/25)
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- Dimerization of indole derivatives with hypervalent iodines(III): A new entry for the concise total synthesis of rac- and meso-chimonanthines
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Hypervalent iodine(III)-induced dimerization of indole derivatives, mitragynine, tetrahydrocarbazole, and Nb-carbomethoxytryptamine, was investigated. By applying this procedure, the concise total synthesis of rac- and meso-chimonanthines was accomplished.
- Ishikawa, Hayato,Takayama, Hiromitsu,Aimi, Norio
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p. 5637 - 5639
(2007/10/03)
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- Synthesis and antinociceptive activity of chimonanthines and pyrrolidinoindoline-type alkaloids
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Hodgkinsine, a trimeric pyrrolidinoindoline type alkaloid, present as a major constituent of Psychotria spp. (Rubiaceae), has shown to produce dose-dependent, naloxone reversible, analgesic effect in thermal models of nociception and in the capsaicin-induced pain. SAR studies have been initiated by synthesizing the three diastereomeric dimers (chimonanthines) (11-13) which were evaluated in vitro and in vivo along with the synthetic intermediates. Strong binding affinities for μ opioid receptors were found for (-)- and (+)-chimonanthine monourethanes (9 and 10), whereas (-)-, (+)- and (meso)-chimonanthine (11-13) and hodgkinsine displayed low affinity. In vivo data have shown that only (+)-chimonanthine (12) and calycosidine resemble the analgesic profile found for hodgkinsine.
- Verotta,Orsini,Sbacchi,Scheildler,Amador,Elisabetsky
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p. 2133 - 2142
(2007/10/03)
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