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Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives
Pyrimidine antimetabolic agents are the essential drugs in treatment of various tumors. Novel synthesis and biological evaluation of the pyrimidine derivatives incorporating selenium element and amino acid carrier as potential antitumor agents have not been tried and studied. Based on the biological significance of pyrimidine structure, these two additional elemental fragments maybe enhance the antitumor effect and reduce toxic side effects of pyrimidine agents. The aim of this paper is to synthesis a series of 4-selenopyrimidine derivatives in order to find more potent lead compounds against cancer. In this study, 12 new 4-selenopyrimidine derivatives that are unstable in acidic solutions but very stable in alkaline and neutral solutions avoiding light were synthesized, and the antitumor activities on HepG2 cell lines of these compounds were evaluated by MTT assay. The results have shown that these compounds could reduce the proliferation of HepG2 cells in a dose-dependent fashion, and the inhibitory activity of compounds a6 was greater than that of positive control 5-fluorouracil (5-FU), the IC50 for a6 was 3.63 μM. In the comprehensive analysis of the structure–activity relationship, we could draw the antitumor effect of selenouracil derivatives is stronger than those of selenothymine derivatives. These results suggest that the substituent groups of selenium element and amino acid on the pyrimidine derivatives are vital for their antitumor activities on HepG2 cells.
Shi, Mingxing,Wang, Libo,Zhang, Long,Wang, Kexin,Zhang, Hualin,Wang, Yajing,Li, Chang,Han, Weina
p. 96 - 116
(2020/10/22)

N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
(2020/04/09)

Cleavable Amide Bond: Mechanistic Insight into Cleavable 4-Aminopyrazolyloxy Acetamide at Low pH
The cleavage of amide bonds under mild acidic conditions is a rare chemical event. N-Acetamide bond of peptides is extremely stable even under the strongest organic acid trifluoromethanesulfonic acid. This report mechanistically describes a new cleavable amide bond in 4-aminopyrazolyloxy acetamide peptide analogues under mild acidic conditions such as trifluoroacetic acid (10-20%) or HCl (0.1-4.0 N) at room temperature, and the formation of unusual lactam from 4-aminopyrazolyloxy acetic acid after evaporation of solvent. This is a rare chemical event in peptide bond, which could be explored as acid-sensitive protecting group of free amines.
Bollu, Amarnath,Sharma, Nagendra K.
supporting information
p. 5596 - 5602
(2019/05/10)

Cleavable Amide Bond: Mechanistic Insight into Cleavable 4-Aminopyrazolyloxy Acetamide at Low pH
The cleavage of amide bonds under mild acidic conditions is a rare chemical event. N-Acetamide bond of peptides is extremely stable even under the strongest organic acid trifluoromethanesulfonic acid. This report mechanistically describes a new cleavable amide bond in 4-aminopyrazolyloxy acetamide peptide analogues under mild acidic conditions such as trifluoroacetic acid (10-20%) or HCl (0.1-4.0 N) at room temperature, and the formation of unusual lactam from 4-aminopyrazolyloxy acetic acid after evaporation of solvent. This is a rare chemical event in peptide bond, which could be explored as acid-sensitive protecting group of free amines.
Bollu, Amarnath,Sharma, Nagendra K.
supporting information

(2019/05/08)

Heterocyclic Compounds from the Mushroom Albatrellus confluens and Their Inhibitions against Lipopolysaccharides-Induced B Lymphocyte Cell Proliferation
Eight hetereocyclic compounds conflamides B-I with an unprecedented skeleton and their precursor conflamide A were isolated from the mushroom Albatrellus confluens. Their structures and absolute configurations were determined by use of NMR studies, total synthesis, and calculated ECD spectra. Conflamides D and E were found to exhibit potent inhibition against LPS-induced B lymphocyte cell proliferation with IC50 values 1.48 and 5.71 μM, respectively.
Zhang, Shuaibing,Huang, Ying,He, Shijun,Chen, Heping,Wu, Bin,Li, Shanyong,Zhao, Zhenzhu,Li, Zhenghui,Wang, Xian,Zuo, Jianping,Feng, Tao,Liu, Jikai
p. 10158 - 10165
(2018/08/03)

Simple and efficient Fmoc removal in ionic liquid
A mild method for an efficient removal of the fluorenylmethoxycarbonyl (Fmoc) group in ionic liquid was developed. The combination of a weak base such as triethylamine and [Bmim][BF4] makes the entire system more efficient for the cleavage at room temperature of various amines and amino acid methyl esters in short reaction times. The procedure works well even in the case of N-Fmoc amino acids bearing acid-sensitive protecting groups and of N-alkylated amino acid methyl esters. The solvent-free condition provides a complementary method for Fmoc deprotection in solution phase peptide synthesis and modern organic synthesis.
Di Gioia,Costanzo,De Nino,Maiuolo,Nardi,Olivito,Procopio
p. 36482 - 36491
(2017/08/02)

COMPOUND, COMPOSITION AND USES THEREOF
The compositions and compounds of formula I, formula II, formula III which includes a salt of polyunsaturated fatty acids in a molecular conjugate with amino acid isoleucine or its polymorphs, enantiomers, stereoisomers, solvates, and hydrates thereof. These salts may be formulated as pharmaceutical compositions. The pharmaceutical compositions may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, intravenous, parenteral administration, syrup, or injection administration. Such compositions may be used to treatment of hyperglycemia, metabolic syndrome, diabetes, pre-diabetes, lowering triglycerides or its associated complications.
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(2017/05/10)

Hydroxy-Directed Amidation of Carboxylic Acid Esters Using a Tantalum Alkoxide Catalyst
We describe herein a new strategy for the chemoselective synthesis of amides by using a metal-catalyzed hydroxy-directed reaction. A hydroxy group located at the β-position of an ester group promoted the activation of a carbonyl group with a tantalum alkoxide catalyst followed by amidation reactions, leading to a wide variety of β-hydroxyamides with excellent chemeselectivity. The chemoselective amidation strategy can be extended to the catalytic synthesis of dipeptide derivatives, which remains challenging research subjects in modern organic synthesis.
Tsuji, Hiroaki,Yamamoto, Hisashi
supporting information
p. 14218 - 14221
(2016/11/13)

Synthesis and biological evaluation of novel lipoamino acid derivatives
Seven novel lipoamino acid conjugates were synthesized from methyl oleate and amino acids. Methyl oleate was grafted to different amino acids using thioglycolic acid as a spacer group. Seven derivatives (3a-g) were prepared and characterized by spectral data (NMR, IR and MS spectral studies). All the derivatives were studied for their antimicrobial, anti-biofilm and anticancer activities. Among all the derivatives, it was found that compound 3b was the most potent antibacterial compound which showed good activity against four Gram positive bacterial strains and also exhibited excellent antifungal activity against a fungal strain. In the anti-biofilm assay, compound 3b showed promising activity with IC50 value of 2.8 μM against Bacillus subtilis MTCC 121. All the compounds showed anticancer activities with 3c showing promising anticancer activity (IC50 = 15.3-22.4 μM) against the four cell lines tested.
Kaki, Shiva Shanker,Arukali, Sammaiah,Korlipara, Padmaja V.,Prasad,Yedla, Poornachandra,Ganesh Kumar
supporting information
p. 209 - 212
(2015/12/20)

Pd-catalyzed coupling of γ-C(sp3)-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides
Pd-catalyzed regioselective coupling of γ-C(sp3)-H bonds of oxalyl amide-protected amino acids with heteroaryl and aryl iodides is reported. A wide variety of iodides are tolerated, giving the corresponding products in moderate to good yields. Various oxalyl amide-protected amino acids were compatible in this C-H transformation, thus representing a practical method for constructing non-natural amino acid derivatives.
Han, Jian,Zheng, Yongxiang,Wang, Chao,Zhu, Yan,Huang, Zhi-Bin,Shi, Da-Qing,Zeng, Runsheng,Zhao, Yingsheng
p. 5681 - 5689
(2016/07/13)

GLYCOAMINO ACID AND USE THEREOF
An object of the present invention is to provide glycoamino acid as an amino acid precursor with improved properties (particularly water-solubility, stability in water, bitter taste etc.). The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a salt thereof.
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(2016/08/17)

Instability of Amide Bond Comprising the 2-Aminotropone Moiety: Cleavable under Mild Acidic Conditions
An unusual hydrolysis/solvolysis of the classical acyclic amide bond, derived from N-troponylaminoethylglycine (Traeg) and α-amino acids, is described under mild acidic conditions. The reactivity of this amide bond is possibly owed to the protonation of the troponyl carbonyl functional group. The results suggest that the Traeg amino acid is a potential candidate for protecting and caging of the amine functional group of bioactive molecules via a cleavable amide bond.
Balachandra, Chenikkayala,Sharma, Nagendra K.
supporting information
p. 3948 - 3951
(2015/09/01)

NOVEL COMPOUND, PHOTOSENSITIVE RESIN COMPOSITION, AND COLOR FLITER
The present invention relates to a novel compound, a photosensitive resin composition comprising the compound and a color filter and, more specifically, to a compound represented by chemical formula 1, a photosensitive resin composition comprising the compound, an alkali-soluble resin, a photopolymerizable compound, a photopolymerization initiator and a solvent, and a color filter manufactured by using the photosensitive resin composition.COPYRIGHT KIPO 2016
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Paragraph 0217; 0218

(2016/11/07)

A mild removal of Fmoc group using sodium azide
A mild method for effectively removing the fluorenylmethoxycarbonyl (Fmoc) group using sodium azide was developed. Without base, sodium azide completely deprotected Nα-Fmoc-amino acids in hours. The solvent-dependent conditions were carefully studied and then optimized by screening different sodium azide amounts and reaction temperatures. A variety of Fmoc-protected amino acids containing residues masked with different protecting groups were efficiently and selectively deprotected by the optimized reaction. Finally, a biologically significant hexapeptide, angiotensin IV, was successfully synthesized by solid phase peptide synthesis using the developed sodium azide method for all Fmoc removals. The base-free condition provides a complement method for Fmoc deprotection in peptide chemistry and modern organic synthesis. Graphical Abstract: [Figure not available: see fulltext.]
Chen, Chun-Chi,Rajagopal, Basker,Liu, Xuan Yu,Chen, Kuan Lin,Tyan, Yu-Chang,Lin, Fui,Lin, Po-Chiao
p. 367 - 374
(2014/03/21)

67/68Ga-labeling agent that liberates 67/68Ga-NOTA-methionine by lysosomal proteolysis of parental low molecular weight polypeptides to reduce renal radioactivity levels
The renal localization of gallium-67 or gallium-68 (67/68Ga)-labeled low molecular weight (LMW) probes such as peptides and antibody fragments constitutes a problem in targeted imaging. Wu et al. previously showed that 67Ga-labeled S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (SCN-Bz-NOTA)-conjugated methionine (67Ga-NOTA-Met) was rapidly excreted from the kidney in urine following lysosomal proteolysis of the parental 67Ga-NOTA-Bz-SCN-disulfide-stabilized Fv fragment (Bioconjugate Chem., (1997) 8, 365-369). In the present study, a new 67/68Ga-labeling reagent for LMW probes that liberates 67/68Ga-NOTA-Met was designed, synthesized, and evaluated using longer-lived 67Ga in order to reduce renal radioactivity levels. We employed a methionine-isoleucine (MI) dipeptide bond as the cleavable linkage. The amine residue of MI was coupled with SCN-Bz-NOTA for 67Ga-labeling, while the carboxylic acid residue of MI was derivatized to maleimide for antibody conjugation in order to synthesize NOTA-MI-Mal. A Fab fragment of the anti-Her2 antibody was thiolated with iminothiolane, and NOTA-MI-Mal was conjugated with the antibody fragment by maleimide-thiol chemistry. The Fab fragment was also conjugated with SCN-Bz-NOTA (NOTA-Fab) for comparison. 67Ga-NOTA-MI-Fab was obtained at radiochemical yields of over 95% and was stable in murine serum for 24 h. In the biodistribution study using normal mice, 67Ga-NOTA-MI-Fab registered significantly lower renal radioactivity levels from 1 to 6 h postinjection than those of 67Ga-NOTA-Fab. An analysis of urine samples obtained 6 h after the injection of 67Ga-NOTA-MI-Fab showed that the majority of radioactivity was excreted as 67Ga-NOTA-Met. In the biodistribution study using tumor-bearing mice, the tumor to kidney ratios of 67Ga-NOTA-MI-Fab were 4 times higher (6 h postinjection) than those of 67Ga-NOTA-Fab. Although further studies including the structure of radiometabolites and/or cleavable linkages are required, the results of the present study indicate that the current chemical design is applicable to the development of 67Ga-labeled Fabs for low renal radioactivity levels.
Uehara, Tomoya,Rokugawa, Takemi,Kinoshita, Mai,Nemoto, Souki,Fransisco Lazaro, Guerra Gomez,Hanaoka, Hirofumi,Arano, Yasushi
p. 2038 - 2045
(2015/02/19)

Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors
Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.
Yang, Dezhi,Wang, Peng,Liu, Jianzhen,Xing, Hualu,Liu, Yang,Xie, Wencheng,Zhao, Guisen
p. 366 - 373
(2014/01/17)

Synthesis of glycopeptoid sulfonamides diversifying N-glycopeptide linkage region mimics
Replacing the planar carboxamides with tetrahedral sulfonamides in the glycopeptoid backbone, glycopeptoid sulfonamides were synthesized as N-glycopeptide mimics with diverse structures using β-peptoid, chiral amino acids and β-amide or β-sulfonamide linked amino acids with different functional groups. The sulfonamide group exists in different conformations and participates in C-H...O interactions.
Singhamahapatra, Anadi,Sahoo, Laxminarayan,Varghese, Babu,Loganathan, Duraikkannu
p. 18038 - 18043
(2014/05/20)

A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition
An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.
Bera, Saurav,Panda, Gautam
p. 3976 - 3985
(2014/06/09)

Deprotection/reprotection of the amino group in α-amino acids and peptides. A one-pot procedure in [Bmim][BF4] ionic liquid
This paper presents an efficient one-pot protocol for the sequential deprotection/reprotection of the α-amino group in α-amino acid and dipeptide methyl esters. [Bmim][BF4] is used as the solvent in the entire process. In particular, the use of the ionic liquid allows for rapid and clean removal of the 4-nitrobenzenesulfonyl (nosyl) group and for facile subsequent tert-butyloxycarbonylation of the free α-amino function under very mild conditions. N-Boc-α-amino acid as well as peptide derivatives are isolated in excellent yields, and do not require any further purification. Absolute configurations of the precursors are totally preserved during the process.
Di Gioia,Barattucci,Bonaccorsi,Leggio,Minuti,Romio,Temperini,Siciliano
p. 2678 - 2686
(2014/01/06)

In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
supporting information
p. 6824 - 6830
(2013/06/26)

Surugamides A-E, cyclic octapeptides with four D-amino acid residues, from a marine streptomyces sp.: LC-MS-aided inspection of partial hydrolysates for the distinction of D- and L-amino acid residues in the sequence
Surugamides A-E (1-5), cyclic octapeptides with four d-amino acid residues, were isolated from the broth of marine-derived Streptomyces sp. Their planar structures were determined by analyses of spectroscopic data, and the absolute configuration of constituent amino acid residues was determined by the Marfey's method. Differentiation of d-Ile and l-Ile in the sequence was established by chiral analysis of fragment peptides obtained from the partial hydrolysate, whose identification was conducted by LC-MS/MS.
Takada, Kentaro,Ninomiya, Akihiro,Naruse, Masato,Sun, Yi,Miyazaki, Masayuki,Nogi, Yuichi,Okada, Shigeru,Matsunaga, Shigeki
p. 6746 - 6750
(2013/07/26)

HR-MALDI-MS imaging assisted screening of β-Carboline alkaloids discovered from mycena metata
Fruiting bodies of Mycena metata were screened for the presence of new secondary metabolites by means of HPLC-UV, LC-HR-ESIMS, and high-resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (HRMALDI- MS imaging). Thus, a new β-carboline alkaloid, 6-hydroxymetatacarboline D (1d), was isolated from fruiting bodies of M. metata. 6-Hydroxymetatacarboline D consists of a highly substituted β-carboline skeleton, which is likely to be derived biosynthetically from L-tryptophan, 2-oxoglutaric acid, L-threonine, and L-proline. The structure of the alkaloid was established by 2D NMR spectroscopic methods and HR-ESIMS. Moreover, by extensive application of LC-HR-ESIMS, LC-HR-ESIMS/MS, and LC-HR-ESIMS3 techniques we were able to elucidate the structures of a number of accompanying β-carboline alkaloids, 1a- 1c, 1e-1i, and 2a-2g, structurally closely related to 6-hydroxymetatacarboline D, which are present in M. metata in minor amounts. The absolute configuration of the stereogenic centers of the β-carboline alkaloids was determined by GC-MS comparison with authentic synthetic samples after hydrolytic cleavage and derivatization of the resulting amino acids.
Jaeger, Robert J. R.,Lamshoeft, Marc,Gottfried, Sebastian,Spiteller, Michael,Spiteller, Peter
p. 127 - 134
(2013/06/27)

Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx
Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.
Kimura, Miki,Wakimoto, Toshiyuki,Egami, Yoko,Tan, Karen Co,Ise, Yuji,Abe, Ikuro
experimental part
p. 290 - 294
(2012/05/05)

Total synthesis of aeruginosin 98B
The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.
Trost, Barry M.,Kaneko, Toshiyuki,Andersen, Neil G.,Tappertzhofen, Christoph,Fahr, Bruce
supporting information
p. 18944 - 18947
(2013/01/15)

I2-mediated diversity oriented diastereoselective synthesis of amino acid derived trans-2,5-disubstituted morpholines, piperazines, and thiomorpholines
Diastereoselective trans-2,5-disubstituted amino acids derived diverse morpholines, piperazines and thiomorpholines were prepared in 30 min-1 h with high yields through iodine-mediated 6-exotrig type cyclization from a single common synthetic intermediate. The displacement of iodine with hydride ion gave a methyl substituent at the 2-position of morpholines which provides an additional opportunity for diversity oriented nucleophilic substitution on the rings as well as incorporation of substituents at the 5-position from amino acids constituents.
Bera, Saurav,Panda, Gautam
scheme or table
p. 1 - 4
(2012/02/16)

Development of tetrahydroisoquinoline-based hydroxamic acid derivatives: Potent histone deacetylase inhibitors with marked in vitro and in vivo antitumor activities
Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibitors (HDACi), among which compound 7d exhibited promising HDAC8 inhibitory and antiproliferative activities. Herein, we report the design and development of a new class of tetrahydroisoquinoline-bearing hydroxamic acid analogues as potential HDACi and anticancer agents. In vitro biological evaluation of these compounds showed improved HDAC8 inhibition (compounds 31a and 31b exhibited mid-nM IC50 values against HDAC8) and potent growth inhibition in multiple tumor cell lines. Most importantly, compounds 25e, 34a, and 34b exhibited excellent in vivo anticancer activities in a human breast carcinoma (MDA-MB-231) xenograft model compared with suberoylanilide hydroxamic acid (SAHA), an approved HDACi. Collectively, our results indicate that tetrahydroisoquinoline bearing a hydroxamic acid is an excellent template to develop novel HDACi as potential anticancer agents.
Zhang, Yingjie,Feng, Jinhong,Jia, Yuping,Wang, Xuejian,Zhang, Lei,Liu, Chunxi,Fang, Hao,Xu, Wenfang
scheme or table
p. 2823 - 2838
(2011/06/22)

Sandwich structure of a ruthenium porphyrin and an amino acid hydrazide for probing molecular chirality by circular dichroism
Owing to the strong Lewis acidity of ruthenium porphyrins, a commercial carbonyl ruthenium porphyrin and an amino acid hydrazide can assemble into a sandwich structure. The nature of such a structure is diagnostic of the absolute configuration of the amino acid by circular dichroism.
Liang, Qing-Feng,Liu, Juan-Juan,Chen, Jian
experimental part
p. 3987 - 3991
(2011/08/09)

Discovery of a tetrahydroisoquinoline-based hydroxamic acid derivative (ZYJ-34c) as histone deacetylase inhibitor with potent oral antitumor activities
Histone deacetylase (HDAC) has emerged as an attractive target for the development of antitumor agents during the past decade. Previously tetrahydroisoquinoline-bearing hydroxamic acid analogue, ZYJ-25e (1), was identified and validated as a potent histone deacetylase inhibitor (HDACi) with marked in vitro and in vivo antitumor potency. In the present study, further modification of 1 led to another more potent, orally active HDACi, ZYJ-34c (4). Compared to FDA-approved drug suberoylanilide hydroxamic acid (SAHA), compound 4 exhibited higher in vivo antitumor potency in a human breast carcinoma (MDA-MB-231) xenograft model and in a mouse hepatoma-22 (H22) pulmonary metastasis model and similar in vivo antitumor potency in a human colon tumor (HCT116) xenograft model.
Zhang, Yingjie,Fang, Hao,Feng, Jinhong,Jia, Yuping,Wang, Xuejian,Xu, Wenfang
scheme or table
p. 5532 - 5539
(2011/10/03)

NOVEL CRYSTALLINE FORMS OF (3R,6R) -3- (2, 3 -DIHYDRO- 1H- INDEN- 2 -YL) - 1 - [ (1R) - 1 - (2, 6 - DIMETHYL - 3 - PYRIDINYL) - 2 - (4 -MORPHOLINYL) -2-OXOETHYL] -6- [(1S) - 1 -METHYLPROPYL] -2,5- PIPERAZINEDIONE
Disclosed are crystalline forms of (3R, 6R)-3-(2,3-dihydro-1 H-inden-2-yl)-1-[(1 R)- 1-(2,6-dimethyl-3-pyridinyl)-2-(4-morpholinyl)-2-oxoethyl]-6-[(1 S)-1-methylpropyl]-2,5- piperazinedione benzenesulfonate salt and pharmaceutical compositions thereof. Also disclosed are processes for the preparation the above compounds and methods for use thereof.
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(2011/05/11)

A class of novel Schiff's bases: Synthesis, therapeutic action for chronic pain, anti-inflammation and 3D QSAR analysis
To discover analgesics for treating chronic pain 17 novel Schiff's bases, N,N′-(Z-allylidene-1,3-diyl)bisamino acid methyl esters were prepared from 1,1,3,3,-tetramethoxypropane and amino acid methyl esters. On tail-flick mouse model 20 μmol/kg of these Schiff's bases were orally administered, the analgesic action started 30 min after administration, reached the maximum 120 min after administration, and at 180 min this action was still observed. On a xylene-induced ear edema mouse model 20 μmol/kg of these Schiff's bases exhibited desirable anti-inflammation. Thus the present Schiff's bases are able to treat chronic pain from inflammation. The effect of the side chains of the amino acid residues of these Schiff's bases on the analgesic activity was explained with 3D QSAR.
Zhou, Yinjian,Zhao, Ming,Wu, Yingting,Li, Chunyu,Wu, Jianhui,Zheng, Meiqing,Peng, Li,Peng, Shiqi
experimental part
p. 2165 - 2172
(2010/05/18)

Facile synthesis of peptide-porphyrin conjugates: Towards artificial catalase
A facile synthetic method for peptide-porphyrin conjugates containing four peptide units on one porphyrin was developed using chemoselective reactions. The key building blocks, 5,10,15,20-tetrakis(3-azidophenyl)porphyrin 1 and 5,10,15,20-tetrakis(5-azido-3-pyridyl)porphyrin 2, were efficiently synthesized and used as substrates for two well-known chemoselective reactions, traceless Staudinger ligation and copper-catalyzed azide alkyne cycloaddition (so-called click chemistry). Both reactions gave the desired compounds, and click chemistry was superior for our purpose. To confirm the value of the established methodology, nine peptide-porphyrin conjugates were synthesized, and their catalase- and peroxidase-like activity in water was evaluated. Our synthetic strategy is expected to be valuable for the preparation of artificial heme protein models.
Umezawa, Naoki,Matsumoto, Nobuyoshi,Iwama, Shinsuke,Kato, Nobuki,Higuchi, Tsunehiko
experimental part
p. 6340 - 6350
(2010/10/04)

Deprotectlon of N-Nosyl-α-amlno acids by using solid-supported mercaptoacetic acid
A simple and efficient synthesis of a solid-supported thiol has been developed. Mercaptoacetic acid was first protected by the dimethoxytrityl group and then anchored to Wang resin through an ester bond. Deprotection of the thiol function led to resin-supported mercaptoacetic acid, a useful supported thiol reagent that can be used in the polymer-assisted solution-phase removal of nosyl (Ns) groups from the amino function of a-amino acids in peptide synthesis.
De Marco, Rosaria,Gioia, Maria Luisa Di,Leggio, Antonella,Liguori, Angelo,Viscomi, Maria Caterina
experimental part
p. 3795 - 3800
(2009/12/05)

Asperelines A-F, peptaibols from the marine-derived fungus Trichoderma asperellum
Fermentation of the marine-derived fungus Trichoderma asperellum, collected from the sediment of the Antarctic Penguin Island, resulted in the isolation of six new peptaibols named asperelines A-F (1-6), which are characterized by an acetylated N-terminus and a C-terminus containing an uncommon prolinol residue. Structures were determined by extensive 1D and 2D NMR (1H- 1H COSY, HMQC, HMBC, NOESY) spectroscopic data analysis combined with ESIMS/MS fragmentation. The absolute configurations of the amino acid residues possessing a chiral R-carbon and of the prolinol residue were determined to be L and S, respectively, using a new method of 1H NMR spectroscopic comparison of complexes formed between the chiral reagent Ru(D 4-Por*)CO and amino acids derived from the peptaibols with those formed with reference standards.
Ren, Jinwei,Xue, Chunmei,Tian, Li,Xu, Minjuan,Chen, Jian,Deng, Zhiwei,Proksch, Peter,Lin, Wenhan
experimental part
p. 1036 - 1044
(2011/02/28)

LCST-type phase changes of a mixture of water and ionic liquids derived from amino acids
(Figure Presented) Out of phase: Ionic liquids (ILs) derived from amino acids exhibit phase separation with a lower critical solution temperature after mixing with water (see picture; upper phase water; lower phase IL). The phase-separation temperature of these mixtures depends on the ion structure and water content, and is lowered by an increase in the hydrophobicity of the ionic liquid.
Fukumoto, Kenta,Ohno, Hiroyuki
p. 1852 - 1855
(2008/02/12)

Azabicyclo[3.1.0]hexane-1-ols as frameworks for the asymmetric synthesis of biologically active compounds
Azabicyclo[3.1.0]hexane-1-ols, easily obtained by Ti(IV)-mediated cyclopropanation of amino acid derivatives, constitute versatile, and unprecedented intermediates for the asymmetric synthesis of pharmacologically active products. Indeed, through selective rearrangement, these compounds undergo unusual ring cleavage to lead to pyrrolidinones. Fe(III)-promoted ring opening followed by basic dehydrohalogenation furnishes optically active dihydropyridinones, while Ce(IV)-promoted ring opening provides chiral tricyclopiperidinones via a radical process.
Jida, Mouhamad,Guillot, Régis,Ollivier, Jean
p. 8765 - 8767
(2008/03/18)

Methods and compositions for treating amyloid-related diseases
Methods, compounds, pharmaceutical compositions and kits are described for treating or preventing amyloid-related disease.
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Page/Page column 138

(2010/11/24)

Alternative and chemoselective deprotection of the α-amino and carboxy functions of N-Fmoc-amino acid and N-Fmoc-dipeptide methyl esters by modulation of the molar ratio in the AlCl3/N,N-dimethylaniline reagent system
The amino and carboxy functions in N-Fmoc-α-amino acid and N-Fmoc-peptide methyl esters can be alternatively and chemoselectively deprotected by treatment with the reagent system AlCl3/N,N- dimethylaniline (DMA). The chemoselectivity of the process is controlled by modulating the relative molar ratio of the Lewis acid and DMA. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
Di Gioia, Maria Luisa,Leggio, Antonella,Le Pera, Adolfo,Liguori, Angelo,Perri, Francesca,Siciliano, Carlo
p. 4437 - 4441
(2007/10/03)

Cyclopeptide alkaloids from Paliurus ramossisimus
Seven zizyphine A-type cyclopeptide alkaloids were isolated from the roots of Paliurus ramossisimus by the combination of centrifugal partition chromatography and conventional separation methods. The novel structures of paliurines A-F (1-6) were characterized and established on the basis of MS and elaborate NMR spectral analyses. Terminal dipeptide stereochemistry was confirmed by correlation with the synthetic dipeptides via comparison of their 13C NMR data.
Lin,Chen,You,Chen Liu,Lee
p. 1338 - 1343
(2007/10/03)

New strategies for an efficient removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the peptide synthesis
The aluminium trichloride/toluene system is investigated as a novel, unusual and straightforward reagent for the removal of the 9- fluorenylmethoxycarbonyl (Fmoc) protecting group in the solution peptide synthesis. This procedure avoids any undesired side reactions, such as the frequently observed inversion of the amino acid configuration.
Leggio, Antonella,Liguori, Angelo,Napoli, Anna,Siciliano, Carlo,Sindona, Giovanni
p. 573 - 575
(2007/10/03)

Selective removal of fluorenylmethoxycarbonyl (FMOC) groups under mild conditions
N-Fluorenylmethoxycarbonyl groups may be removed by potassium fluoride/18- crown-6 in the presence of methyl, ethyl, tert-butyl, benzyl, and p- methoxybenzyl esters.
Jiang,Li,Joullie
p. 187 - 195
(2007/10/02)

TOTAL SYNTHESIS OF THE DIDEMNINS - 1. SYNTHESIS OF THE PEPTOLIDE RING
The 23-membered peptolide ring of the didemnins is formed in a two phase cyclization of a linear ω-amino-pentafluorophenyl ester in 70percent yield without high dilution. (2RS,4S)-2,5-dimethyl-4-hydroxy-3-oxohexanoic acid (Hip) and (3S,4R,5S)-isostatine are synthesized by acylations of trimethylsilyl malonates.
Schmidt, U.,Kroner, M.,Griesser, H.
p. 3057 - 3060
(2007/10/02)

Ergotalkaloids for treating senile dementia
An ergot 5'S-(2R-butyl) peptide alkaloid and its acid addition salts is a useful pharmaceutical for use as a prolactin secretion inhibitor, for increasing vigilance or for the treatment of senile dementia, hypertension, or stroke.
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(2008/06/13)