- 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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- Elucidation of absolute configuration of ophiorrhiside a by comparison of ecd spectra with that of model chiral compound having a 1,2,3,4-tetrahydro-β-carbolin-3-one skeleton
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A chiral 1,2,3,4-tetrahydro-β-carbolin-3-one having a substituent at C-1 was synthesized from L-leucine and used to elucidate the absolute configuration at C-3 of ophiorrhiside A, a monoterpenoid glucoindole alkaloid.
- Onozawa, Tadayoshi,Kogure, Noriyuki,Takayama, Hiromitsu,Kitajima, Mariko
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof (1) wherein each of R1, R2, R3, R4, L1, and L2, are as defined herein. The present invention also contemplates compositions and methods of treatment as an endoparasiticide with a Formula (1) compound.
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Page/Page column 56; 57
(2019/06/17)
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- ENDOPARASITIC DEPSIPEPTIDES
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The present invention provides cyclic depsipeptides of Formula (1), stereoisomers thereof, and veterinary acceptable salts thereof wherein each of R1, R2, R3, R4, L1, and L2 are as defined herein. The present invention also contemplates compositions, methods of treatment, and uses as a medicament to treat an animal for an endoparasitic infection with a Formula (1 ) compound.
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Page/Page column 44; 45
(2019/11/28)
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- Antineoplastic activity of linear leucine homodipeptides and their potential mechanisms of action
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Galaxamide is a rare cyclic homopentapeptide composed of three leucines and two N-methyl leucines isolated from marine algae Galaxaura filamentosa. The strong antitumor activity of this compound makes it a promising candidate for tumor therapy. The synthesis of galaxamide, however, is a complex process, and it has poor water solubility. On the basis of its special chemical composition, we designed a series of linear leucine homopeptides. Among seven dipeptide derivatives, five compounds with terminal protection groups and methyl substitution of the hydrogen in the amido group showed remarkable inhibitory effects against various cancer cells. N-Tertbutyl-d-leucine-N-methyl-d-leucinebenzyl (A7), the only stereomer condensed by two d-leucines, showed the highest antineoplastic activity. A7-Treated cells showed cell cycle arrest and morphological changes typical of cells undergoing apoptosis. The population of Annexin-V positive/propidium iodide-negative cells also increased, indicating the induction of early apoptosis. A7 promoted the cleavage of caspase-9 and caspase-3, as well as increased intracellular Ca 2+ levels and decreased the mitochondrial membrane potential. Collectively, certain linear leucine dipeptides derived from cyclic pentapeptide are able to inhibit tumor cell proliferation through cell cycle arrest and apoptosis induction. The N-methyl group in the side chain and the d/l conformation of the amino-Acid residue are critical for their activity.
- Lei, Yun,Yang, Xiao-Xia,Guo, Wei,Zhang, Fu-Yong,Liao, Xiao-Jian,Yang, Hui-Fu,Xu, Shi-Hai,Xiong, Sheng
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p. 503 - 512
(2018/06/04)
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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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- Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
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Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
- Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
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p. 1148 - 1162
(2016/07/06)
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- Total synthesis of proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide
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Total synthesis of the originally proposed structure of coibamide A, a highly N- and O-methylated cytotoxic marine cyclodepsipeptide, has been accomplished by using a [(4+1)+3+3]-peptide fragment-coupling strategy and careful examination and optimization
- He, Wei,Qiu, Hai-Bo,Chen, Yi-Jie,Xi, Jie,Yao, Zhu-Jun
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supporting information
p. 6109 - 6112
(2015/01/09)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
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The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
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Page/Page column 112
(2014/11/13)
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- Selective peptide modifications via ruthenium-catalyzed allylic alkylations
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Ruthenium-catalyzed allylic alkylations are an interesting alternative to palladium-catalyzed processes, since they can provide products which are not accessible under Pd-catalysis. Chiral terminal allylic substrates can be reacted with perfect stereo- and regioretention, and also (Z)-configured allylic substrates can be converted isomerization-free. This allows highly stereoselective modifications of peptides at glycine subunits. The configuration at the α-position of the new generated α-amino acid can be controlled by the chiral peptide chain, and at the β-position by using chiral allylic substrates.
- Bayer, Anton,Kazmaier, Uli
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p. 8491 - 8497
(2015/03/18)
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- Design, SAR, angiogenic activities evaluation and pro-angiogenic mechanism of new marine cyclopeptide analogs
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Angiogenesis plays an important role in a wide range of physiological processes. In this paper, we designed and synthesized a series of new analogs including 11 line-peptides and 9 cyclo-peptides by using a marine cyclopeptide (compound 21) which could st
- Li,Lu,Wu,Yu,Xu,Qiu,Pei,Lin,Pang
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p. 1183 - 1194
(2013/07/28)
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- Study of intramolecular aminolysis in peptides containing N-alkylamino acids at position 2
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Many peptides and proteins, containing Nα-alkylamino acids (including proline) at the second position, are prone to intramolecular aminolysis (IA) with elimination of N-terminal dipeptide sequence as 2,5-diketopiperazines (DKP). We synthesized a series of short peptides, containing N-alkylamino acids at position 2, and studied their stability in the presence of acetic acid and amines. The presence of side chains in the second and the third amino acid residues and alkylation at Nα of the third amino acid residue slowed down IA. Nα-Alkyl residue in the first amino acid residue impeded IA only in peptides, containing three or more residues. Side chains of the first amino acids did not affect significantly the cleavage rates. Acetic acid promoted IA more strongly than aqueous ammonia, while tertiary amines were less effective. Peptides with methionine-S-oxide residues were more labile than the unoxidized analogs, suggesting intramolecular assistance of the S-oxide group in aminolysis. Surprisingly, intermediate compounds of the formula Boc-Met-MeXaa-Sar-NHR underwent rapid cleavage (endopeptolysis) upon attempted acidolytic deprotection.
- Ryakhovsky, Vladimir V.,Ivanov, Andrey S.
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p. 7070 - 7076
(2012/08/29)
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- N, N′ -methyleno-didemnin A from the ascidian trididemnum solidum. Complete NMR assignments and confirmation of the imidazolidinone ring by strategic analysis of 1 J CH
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The complete NMR assignments of N,N′-methyleno-didemnin A from Trididemnum solidum Van Name 1902 are reported along with a strategic analysis of 1JCH coupling constants that confirm the presence of the imidazolidinone ring.
- Molinski, Tadeusz F.,Ko, Jaeyoung,Reynolds, Kirk A.,Lievens, Sarah C.,Skarda, Katrina R.
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scheme or table
p. 882 - 887
(2011/06/21)
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- Formamides derived from N-methyl amino acids serve as new chiral organocatalysts in the enantioselective reduction of aromatic ketimines with trichlorosilane
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Asymmetric reduction of N-aryl ketimines 1a-k, 43, and 45 with trichlorosilane can be catalyzed by new N-methyl l-amino acid-derived Lewis-basic organocatalysts, such as the valine-derived bisamide 3d (10 mol%), in toluene at room temperature with high enantioselectivity (≤92% ee). The structure-reactivity investigation shows that the product configuration is controlled by the nature of the side chain of the catalyst scaffold (e.g., i-Pr vs Me, as in 3d and 6e), so that catalysts of the same absolute configuration may induce the formation of the opposite enantiomers of the product. Arene-arene interactions between the catalyst and the incoming imine appear to be the prerequisite for asymmetric induction. This metal-free, organocatalytic protocol is competitive with the traditional, metal-catalyzed methodology.
- Malkov, Andrei V.,Ston?ius, Sigitas,MacDougall, Kenneth N.,Mariani, Andrea,McGeoch, Grant D.,Ko?ovsky, Pavel
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p. 264 - 284
(2007/10/03)
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- An efficient and practical N-methylation of amino acid derivatives.
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[reaction: see text] An efficient and practical N-methylation of amino acid derivatives with dimethyl sulfate in the presence of sodium hydride and a catalytic amount of water is described. Reaction of water with sodium hydride generated highly reactive dry sodium hydroxide, which led to much faster reaction rates than powdered sodium hydroxide itself.
- Prashad, Mahavir,Har, Denis,Hu, Bin,Kim, Hong-Yong,Repic, Oljan,Blacklock, Thomas J
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p. 125 - 128
(2007/10/03)
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- A simple and rapid protocol for N-methyl-α-amino acids
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A two step strategy for optically pure N-Protected-N-methyl-α-amino acids starting from N-protected-α-amino acids via reductive cleavage of oxazolidinones using NaCNBH3/TMSCl is described.
- Reddy, G. Vidyasagar,Iyengar
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p. 299 - 300
(2007/10/03)
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- A practical approach for the optically pure N-Methyl-α- amino acids
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A new practical synthesis of N-Methyl-α-amino acids by racemization free methodology has been developed. The method involves the reductive cleavage of N-protected oxazotidinones using hydrogen in the presence of Pd/C to give the title compounds in quantitative yields.
- Reddy, G. Vidyasagar,Rao, G. Venkat,Iyengar
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p. 1985 - 1986
(2007/10/03)
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- Rational design and synthesis of unsaturated 2,5-dioxopiperazine derivatives as potential protein tyrosine kinase inhibitors
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The first general method for the synthesis of a library of trifunctionalized (Z)-3-alkylidene-2,5-piperazinediones as potential protein tyrosine kinase inhibitors from commercially available amino compounds, α- keto acids and aldehydes using a novel cyclization/cleavage strategy on solid support is described.
- Li, Wen-Ren,Peng, Shao-Zheng
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p. 7373 - 7376
(2007/10/03)
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- A highly efficient method of N-methylation for the amino acid derivatives
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Many naturally occurring, biologically active cyclic peptides are found to contain several N-methyl amino acid constituents.A method has been found out for the N-methylation of amino acid derivatives using sodium hexamethyl disilazide and methyl iodide which gives very good yield without the racemisation.
- Belagali, Shiddappa L.,Mathew, Thankamma,Himaja, M.,Kocienski, Philip
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- Peptide Enolates. C-Alkylation of Glycine Residues in Linear Tri-, Tetra-, and Pentapeptides via Dilithium Azadienediolates
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The Boc-protected tripeptides Boc-Val-Gly-Leu-OH (1), Boc-Leu-Sar-Leu-OH (2), Boc-Leu-Gly-MeLeu-OH (3), and Boc-Val-BzlGly-Leu-OMe (64), tetrapeptide Boc-Leu-Gly-Pro-Leu-OH (9), and pentapeptides Boc-Val-Leu-Gly-Abu-Ile-OH (4), Boc-Val-Leu-Sar-MeAbu-Ile-O
- Bossler, Hans G.,Seebach, Dieter
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p. 1124 - 1165
(2007/10/02)
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- Total Synthesis of the Anthelmintic Cyclodepsipeptide, PF1022A
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The anthelmintic cyclooctadepsipeptide PF1022A and its antipode were synthesized starting from L-Nα-Boc-leucine (for PF1022A), D-N4a-Boc-leucine (for the antipode), L-lactic acid, and L-phenyllactic acid using Mitsunobu reaction and/
- Ohyama, Makoto,Iinuma, Katsuharu,Isogai, Akira,Suzuki, Akinori
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p. 1193 - 1194
(2007/10/02)
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- Synthesis of new indolactam analogues by microbial conversion
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Ten indolactam congeners with L-Ala, Abu, γ,δ-Δ-Nva, Nva, Nle, tert-Leu, Leu, Ile, allo-Ile. Phg instead ofL-Val in (-)-indolactam-Val, were synthesized from their seco-compounds (N-methyl-L-amino acidyl-L-tryptophonol) by microbial conversion.
- Kajiyama, Shin-Ichiro,Irie, Kazuhiro,Kido, Takae,Koshimizu, Koichi,Hayashi, Hideo,Arai, Motoo
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p. 5453 - 5462
(2007/10/02)
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