- Preparation method of N-trimethyl silicon ethoxycarbonyl-N-methyl-L/D-leucine
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The invention relates to a preparation method of N-(trimethylsilyl) ethoxycarbonyl group-N-methyl-L/D-leucine. The preparation method comprises the following steps: adding N-methyl-L/D-leucine hydrochloride, a trimethylsilylethoxycarbonyl protecting group reagent and alkali into a mixed solution of a polar solvent and water, and carrying out a reaction, so as to obtain the N-trimethylsilylethoxycarbonyl-N-methyl-L/D-leucine. According to the preparation method, the N-trimethyl silicon ethoxycarbonyl-N-methyl-L/D-leucine with high chiral purity, high chemical purity and high yield can be obtained, the chiral purity and the chemical purity can reach 99% or above, the yield can reach 60% or above, and the preparation method is simple in process, mild in condition and suitable for being applied to large-scale industrial production.
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Paragraph 0084; 0087; 0090; 0093
(2021/06/02)
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- D-amino acid position influences the anticancer activity of galaxamide analogs: An apoptotic mechanism study
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Galaxamide, an extract from Galaxaura filamentosa, is a cyclic pentapeptide containing five L-leucines. Due to the particular cyclic structure and the excellent anticancer activity, synthesis of Galaxamide and its analogs and their subsequent bio-applications have attracted great attention. In the present work, we synthesized six Galaxamide analogs by replacing one of the L-leucines with phenylalanine and varying the D-amino acid position. The anticancer effect of the synthesized Galaxamide analogs was tested against four in vitro human cancer cell lines, human hepatocellular cells (HepG2), human breast cancer cell (MCF-7), human breast adenocarcinoma cells (MDA-MB-435) and a human cervical carcinoma cell line (Hela). Results showed that Galaxamide analogs with differentD-amino acid positions displayed distinct anticancer potential. The Galaxamide analog containing D-amino acid at position 5 (Analog-6) presented the strongest anticancer activity. The mechanism study revealed that Analog-6 could cause the early apoptosis of HepG2 cells by inhibiting their growth in the sub-G1 stage of the cell cycle and induce the chromatin condensation and fragmentation, which can be seen as 68% of HepG2 cells inhibited in the sub-G1 stage. Moreover, a mitochondria-mediated pathway was found to be involved in the apoptotic process of Analog-6 on HepG2 cells.
- Bai, Defa,Yu, Siming,Zhong, Shenghui,Zhao, Bingxin,Qiu, Shaoling,Chen, Jianwei,Lunagariya, Jignesh,Liao, Xiaojian,Xu, Shihai
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- HETEROCYCLIC KINASE INHIBITORS
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The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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Page/Page column 104
(2016/05/19)
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- Efficient total synthesis of didemnins A and B
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Didemnins A and B (1 and 2), cytotoxic cyclic peptides from a Caribbean tunicate Trididemnum solidum, have been efficiently prepared by a convergent scheme from two key eastern and western fragments. Efficient routes to derivatives of the constituents of didemnis were explored. Benzyl (2RS,4S)-[O-(tert-butyldimethylsilyl)hydroxyisovaleryl]propionate (Hip derivative) was prepared from 2-hydroxyisovaleric acid by use of C-acylation of Meldrum's acid with diethyl phosphorocyanidate as a key step. Derivatives of (3S,4R,5S)-isostatine (Ist) were prepared from Boc-(R)-alloisoleucine. Methylation of Boc-(R)-Leu-OH and Z-(S)-Tyr-OH respectively afforded the corresponding N-methyl and N,O-dimethyl derivatives. The key eastern fragment, (2RS,4S)-Hip-(S)-Leu-(S)-Pro-OBzl (3), was prepared stepwise from (S)-Pro-OBzl, while Boc-(R)-MeLeu-(S)-Thr[Z-(S)-MeTyr(Me)]-(3S,4R,5S)-Ist(TBDMS)-OH (4), the key western fragment for didemnin A (1), was prepared from Ist derivatives. Coupling of 3 with 4 and cyclization, followed by deprotection, afforded didemnin A (1), which was converted to didemnin B (2).
- Hamada,Kondo,Shibata,Shioiri
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p. 669 - 673
(2007/10/02)
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