- Ribose conversion with amino acids into pyrraline platform chemicals-expeditious synthesis of diverse pyrrole-fused alkaloid compounds
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One-pot conversion of sustainable d-ribose with l-amino acid, methyl esters produced pyrrole-2-carbaldehydes 5 in reasonable yields (32-63%) under pressurized conditions of 2.5 atm at 80 °C. The value-added pyrraline compounds 5 as platform chemicals were utilized for quick installation of poly-heterocyclic cores for the development of pyrrole-motif natural and artificial therapeutic agents. A pyrrole-fused piperazin-2-one scaffold 6 was prepared by reductive amination of pyrralines 5 with benzylamine. While further cyclization of pyrralines 5 with ethane-1,2-diamine produced pyrrolo-piperazin-2-ones 7 with an extra imidazolidine ring, the reaction with 2-amino alcohols derived from natural l-amino acids, alanine, valine, and phenylalanine, respectively provided pyrrolo-piperazin-2-ones 8, 9, and 10 with oxazolidine as the third structural core. Cell viability and an anti-inflammatory effect of the synthesized compounds were briefly tested by the MTT method and the Griess assay, among which 8h and 10g exhibited significant anti-inflammatory effects with negligible cell toxicity.
- Cho, Soohyeon,Gu, Lina,In, Ik Joon,Kim, Hakwon,Koo, Sangho,Lee, Taehoon,Wu, Bo
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p. 31511 - 31525
(2021/11/30)
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- Optimization of N-Phenylpropenoyl- l -amino Acids as Potent and Selective Inducible Nitric Oxide Synthase Inhibitors for Parkinson's Disease
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N-Phenylpropenoyl-l-amino acids (NPAs) are inducible nitric oxide synthase (iNOS) inhibitors possessing preventive effects for Parkinson's disease (PD). Here, structural modifications for improving the iNOS inhibitory activity and blood-brain barrier (BBB) permeability of NPAs were conducted, leading to 20 optimized NPA derivatives (1-20). Compound 18, with the most potent activity (IC50 = 74 nM), high BBB permeability (Pe = 19.1 × 10-6 cm/s), and high selectivity over other NOS isoforms, was selected as the lead compound. Further studies demonstrated that 18 directly binds to iNOS. In the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced acute PD model, the oral administration of 18 (1 and 2 mg/kg) exerted preventive effects by alleviating the loss of dopaminergic (DAergic) neurons. Notably, in the MPTP-/probenecid-induced chronic PD model, the same dose of 18 also displayed a therapeutic effect by repairing the damaged DAergic neurons. Finally, good pharmacokinetic properties and low toxicity made 18 a promising candidate for the treatment of PD.
- Hu, Xiao-Long,Lv, Xian-Yu,Wang, Rong,Long, Huan,Feng, Jia-Hao,Wang, Bao-Lin,Shen, Wei,Liu, Hao,Xiong, Fei,Zhang, Xiao-Qi,Ye, Wen-Cai,Wang, Hao
-
p. 7760 - 7777
(2021/06/28)
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- Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
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Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
- Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
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p. 1057 - 1072
(2020/08/13)
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- Design, synthesis and anxiolytic activity evaluation of N-Acyltryptophanyl- containing dipeptides, potential TSPO ligands
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Background: The 18 kDa translocator protein (TSPO), previously known as the peripheral- type benzodiazepine receptor, plays a key role for the synthesis of neurosteroids by promoting transport of cholesterol from the outer to the inner mitochondrial membrane, which is the ratelimiting step in neurosteroid biosynthesis. Neurosteroids interact with nonbenzodiazepine site of GABAa receptor causing an anxiolytic effect without the side effects. Methods: Using the original peptide drug-based design strategy, the first putative dipeptide ligand of the TSPO N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23) was obtained. Molecular docking of GD-23 in the active pocket of the TSPO receptor using Glide software was carried out. The lead compounds GD-23 and its analogues were synthesized using activated succinimide esters coupling method. The anxiolytic activity of GD-23 and its analogues was investigated in vivo, using two validated behavioral tests, illuminated open field and elevated plus-maze. Results: The in vivo studies revealed that the following parameters are necessary for the manifestation of anxiolytic activity of new compounds: the L-configuration of tryptophan, the presence of an amide group at the C-terminus, the specific size of the N-acyl substituent at the Nterminus. Compound GD-23 (N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide) demonstrated a high anxiolytic-like effect in the doses of 0.05-1.0 mg/kg i.p. comparable with that of diazepam. Compound GD-23 was also active in the open field test when was administered orally in the doses of 0.1-5.0 mg/kg. The involvement of TSPO receptor in the mechanism of anxiolytic-like activity of new compounds was proved by the antagonism of compound GD-23 with TSPO selective inhibitor PK11195 as well as with inhibitors of enzymes which are involved in the biosynthesis of neurosteroids, trilostane and finasteride. Conclusion: A series of N-acyl-tryptophanyl-containing dipeptides were designed and synthesized as 18 kDa translocator protein (TSPO) ligands. Using a drug-based peptide design method a series of the first dipeptide TSPO ligands have been designed and synthesized and their anxiolytic activity has been evaluated. In general, some of the compounds displayed a high level of anxiolytic efficacy comparable with that of diazepam. The involvement of TSPO receptor in the mechanism of anxiolytic activity of new compounds was proved using two methods. On this basis, the N-acyl-Ltryptophanyl- isoleucine amides could potentially be a novel class of TSPO ligands with anxiolytic activity.
- Deeva, Olga A.,Dyabina, Alina S.,Gudasheva, Tatiana A.,Mokrov, Grigory V.,Seredenin, Sergey B.,Yarkova, Milada A.
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p. 383 - 399
(2019/07/12)
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- Mechanistic Studies on the Organocatalytic α-Chlorination of Aldehydes: The Role and Nature of Off-Cycle Intermediates
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Herein we report the isolation and characterization of aminal intermediates in the organocatalytic α-chlorination of aldehydes. These species are stable covalent ternary adducts of the substrate, the catalyst and the chlorinating reagent. NMR-assisted kinetic studies and isotopic labeling experiments with the isolated intermediate did not support its involvement in downstream stereoselective processes as proposed by Blackmond. By tuning the reactivity of the chlorinating reagent, we were able to suppress the accumulation of rate-limiting off-cycle intermediates. As a result, an efficient and highly enantioselective catalytic system with a broad functional group tolerance was developed.
- Ponath, Sebastian,Menger, Martina,Grothues, Lydia,Weber, Manuela,Lentz, Dieter,Strohmann, Carsten,Christmann, Mathias
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supporting information
p. 11683 - 11687
(2018/09/10)
-
- Ligand-Enabled γ-C(sp3)–H Acetoxylation of Triflyl-Protected Amines
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A palladium-catalyzed γ-C(sp3)–H acetoxylation of triflyl-protected amines has been achieved. The use of pyridine or 2-alkoxyquinoline-type ligands is key to the success of this transformation. The reaction is highly diastereoselective and easily scalable, and constitutes a direct approach for the synthesis of γ-hydroxy-α-amino acids and β,γ-dihydroxy amines, which are not readily accessible by other routes.
- Jia, Wen-Liang,Fernández-Ibá?ez, M. ángeles
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supporting information
p. 6088 - 6091
(2018/09/14)
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- NMR-based assignment of isoleucine: Vs. allo -isoleucine stereochemistry
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A simple 1H and 13C NMR spectrometric analysis is demonstrated that permits differentiation of isoleucine and allo-isoleucine residues by inspection of the chemical shift and coupling constants of the signals associated with the proton and carbon at the α-stereocentre. This is applied to the estimation of epimerisation during metal-free N-arylation and peptide coupling reactions.
- Anderson, Zoe J.,Hobson, Christian,Needley, Rebecca,Song, Lijiang,Perryman, Michael S.,Kerby, Paul,Fox, David J.
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supporting information
p. 9372 - 9378
(2017/11/22)
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- NOVEL HDAC INHIBITORS AND METHODS OF TREATMENT USING THE SAME
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Disclosed herein are novel HDAC inhibitors. The HDAC inhibitors may be used in methods of treating cancer. The HDAC inhibitors may be used in methods of treating a neurological disorder.
- -
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Paragraph 000189
(2017/03/21)
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- LAT1 activity of carboxylic acid bioisosteres: Evaluation of hydroxamic acids as substrates
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Large neutral amino acid transporter 1 (LAT1) is a solute carrier protein located primarily in the blood–brain barrier (BBB) that offers the potential to deliver drugs to the brain. It is also up-regulated in cancer cells, as part of a tumor's increased metabolic demands. Previously, amino acid prodrugs have been shown to be transported by LAT1. Carboxylic acid bioisosteres may afford prodrugs with an altered physicochemical and pharmacokinetic profile than those derived from natural amino acids, allowing for higher brain or tumor levels of drug and/or lower toxicity. The effect of replacing phenylalanine's carboxylic acid with a tetrazole, acylsulfonamide and hydroxamic acid (HA) bioisostere was examined. Compounds were tested for their ability to be LAT1 substrates using both cis-inhibition and trans-stimulation cell assays. As HA-Phe demonstrated weak substrate activity, its structure–activity relationship (SAR) was further explored by synthesis and testing of HA derivatives of other LAT1 amino acid substrates (i.e., Tyr, Leu, Ile, and Met). The potential for a false positive in the trans-stimulation assay caused by parent amino acid was evaluated by conducting compound stability experiments for both HA-Leu and the corresponding methyl ester derivative. We concluded that HA's are transported by LAT1. In addition, our results lend support to a recent account that amino acid esters are LAT1 substrates, and that hydrogen bonding may be as important as charge for interaction with the transporter binding site.
- Zur, Arik A.,Chien, Huan-Chieh,Augustyn, Evan,Flint, Andrew,Heeren, Nathan,Finke, Karissa,Hernandez, Christopher,Hansen, Logan,Miller, Sydney,Lin, Lawrence,Giacomini, Kathleen M.,Colas, Claire,Schlessinger, Avner,Thomas, Allen A.
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supporting information
p. 5000 - 5006
(2016/10/05)
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- Synthesis, toxicity and chemo-sensitization of HeLa cells to etoposide, of some 2-methyl amino acid ester-substituted-1,3-benzoxazines
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A number of new L- or LD-2-amino acid ester-(substituted)-benz[1,3]oxazines 12-17 were synthesized from the reaction of free L- or LD-amino acid ester 9a-d with 2-methylthio-1,3-benzoxazines 11a-g. The structures of the new products 12-17 were confirmed from their 1H, 13CNMR and IR spectra and CHN microanalysis. Some of these compounds weakly inhibited DNA-PK and platelet aggregation. Studies of the toxicity for some of the new compounds showed mostly no inhibitory effects on HeLa cell growth at 1 and 10 μM and some up to 40 μM. The chemo-sensitization to etoposide by some of the compounds revealed that the most effective chemo-sensitizers at 10 μM were 14c (1.83 fold), 12e (1.42 fold), 15a (0.8 fold), 16d (0.76 fold) and 1c (0.74). However, at 1 μM in the presence of etoposide, some compounds were shown to be more effective. No direct link was observed between the type of the L-amino acid methyl ester as well as the 7-, 8-, or 7, 8-substitution on the aromatic ring on the effectiveness of the chemo-sensitizers; however, the 7-hydroxy group did lower the effective chemo-sensitizers values.
- Ihmaid, Saleh K.,Fitzgibbon, Cheree,Al-Rawi, Jasim M. A.
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p. 2825 - 2837
(2015/02/19)
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- Total synthesis of stylissatin A, a cyclic peptide that inhibits nitric oxide production
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Stylissatin A is a proline-rich cyclic heptapeptide isolated from the Papua New Guinean marine sponge Stylissa massa. The first synthesis of stylissatin A was achieved by a combination of solid-phase and solution-phase peptide synthesis. The natural and synthetic samples of stylissatin A showed comparable inhibitory effects on nitric oxide production with negligible cytotoxicity in lipopolysaccharide (LPS)-stimulated murine macrophage RAW264.7 cells (EC50 = 73 μM for synthetic sample). Furthermore, while the D-allo-Ile5 epimer was less potent, a tert-butyl ether analog of stylissatin A was approximately six times more potent than the natural product (EC50 = 12 μM).
- Akindele, Tito,Gise, Baro,Sunaba, Taiki,Kita, Masaki,Kigoshi, Hideo
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p. 600 - 609
(2015/09/21)
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- Efficient asymmetric addition of diethylzinc to aldehydes using C 2-novel chiral pyridine β-amino alcohols as chiral ligands
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A series of novel C2-symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1H NMR, 13C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2R)-2,2-((pyridine-2,6-diylbis(methylene)) bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2R)-2,2-((1,3-phenylenebis(methylene)) bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright
- Zhang, Weijie,Tang, Ruiren,Yu, Huirong,Gao, Shu
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p. 545 - 551
(2014/07/07)
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- Design, synthesis and biological evaluation of novel L-isoserine tripeptide derivatives as aminopeptidase N inhibitors
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Aminopeptidase N (APN/CD13) is one of the essential proteins for tumour invasion, angiogenesis and metastasis as it is over-expressed on the surface of different tumour cells. Based on our previous work that L-isoserine dipeptide derivatives were potent APN inhibitors, we designed and synthesized L-isoserine tripeptide derivatives as APN inhibitors. Among these compounds, one compound 16l (IC50=2.51±0.2 M) showed similar inhibitory effect compared with control compound Bestatin (IC50=6.25±0.4 M) and it could be used as novel lead compound for the APN inhibitors development as anticancer agents in the future.
- Pan, Huili,Yang, Kanghui,Zhang, Jian,Xu, Yingying,Jiang, Yuqi,Yuan, Yumei,Zhang, Xiaopan,Xu, Wenfang
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p. 717 - 726
(2013/07/26)
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- Synthesis of novel 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-ones and 1,2,4-triazin-6(5H)-ones from optically active α-aminocarboxylic acid hydrazides
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New derivatives of 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-one and 1,2,4-triazin-6(5H)-one were synthesized via reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The factors influencing the formation of the unexpected five-membered products and attempts to elucidate the mechanism are discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech,Jasiak, Karolina
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supporting information
p. 4637 - 4640
(2013/08/23)
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- Cycloforskamide, a cytotoxic macrocyclic peptide from the sea slug Pleurobranchus forskalii
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A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug Pleurobranchus forskalii, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral-phase gas chromatographic analysis. This novel dodecapeptide contains three d-amino acids and three thiazoline heterocycles and exhibits cytotoxicity against murine leukemia P388 cells, with an IC 50 of 5.8 μM.
- Tan, Karen Co,Wakimoto, Toshiyuki,Takada, Kentaro,Ohtsuki, Takashi,Uchiyama, Nahoko,Goda, Yukihiro,Abe, Ikuro
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p. 1388 - 1391
(2013/08/23)
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- An efficient synthetic approach for N-C bond formation from (S)-amino acids: An easy access to cis-2,5-disubstituted chiral piperazines
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An efficient synthetic strategy is described for the construction of amino acids derived enantiomerically pure cis-2,5-disubstituted chiral piperazines. Cu-catalyzed spontaneous regioselective ring opening and ring closing of non-activated N-tosyl aziridines as well as Pd-mediated N-C bond formation from N-tosyl halogenated amino-derivatives are the key steps for accessing disubstituted piperazines.
- Manna, Sudipta Kumar,Panda, Gautam
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p. 18332 - 18338
(2013/10/21)
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- Molecular architectonics of stereochemically constrained π-complementary functional modules
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The elucidation of the complex factors that govern recognition events at the molecular level represents a daunting challenge in our quest to master the art of pre-programmed molecular assemblies. In this context, we present the molecular architectonics of thoughtfully designed amino acid appended functional molecules 1-5. Naphthalenediimide (NDI and pyrene were employed as functional modules due to their unusual topological shape similarity as well as complementary π-acidic and π-basic character, respectively. In addition, we show that dyads of such unusual functional modules energetically favour alternate assembly in contrast to the predominant self-sorted assembly observed for single-component systems. Moreover, by incorporating minute structural mutations into the amino acid side-chains of 1-5, we successfully tailored their assemblies into well-defined supramolecular architectures, namely supercoiled helices, twisted nanoribbons, nanobelts, comb-edged nanoflakes and nanosheets. A detailed analysis with the aid of experimental and theoretical studies has generated interesting insights into the factors that govern the recognition events at the molecular level. In a quest to master pre-programmed molecular assemblies, we show that alternate stacking over self-sorting of functional aromatic modules can be energetically controlled by smarter molecular design. Furthermore, by introducing structural mutations into the side-chain of amino acid auxiliaries, the molecular assemblies form tailored well-defined 1D and 2D supramolecular nanoarchitectures. Copyright
- Avinash,Samanta, Pralok K.,Sandeepa,Pati, Swapan K.,Govindaraju
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p. 5838 - 5847
(2013/09/23)
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- Highly tunable arylated cinchona alkaloids as bifunctional catalysts
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We report the design and evaluation of a library of chiral bifunctional organocatalysts in which the distance between the catalytically active units can be systematically varied.
- Quigley, Cormac,Rodriguez-Docampo, Zaida,Connon, Stephen J.
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supporting information; scheme or table
p. 1443 - 1445
(2012/03/11)
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- Synthesis and biological evaluation of novel potent angiotensin II receptor antagonists with anti-hypertension effect
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A series of novel angiotensin II type 1 receptor antagonists were prepared. Radioligand binding assay suggested that compounds 1b and 1c could be recognized by the AT1 receptor with an IC50 value of 1.6 ± 0.09 nM and 2.64 ± 0.7 nM, respectively. In vivo anti-hypertension experiments showed that compounds (1a, 1b, 1c, 1e) elicited a significant decrease in SBP and DBP of spontaneous hypertensive rats (SHRs). The antihypertensive effects maintained for 10 h, which indicated that these compounds had a favorable blood pressure-lowering effect. Acute toxicity testing suggested that the LD50 value of compound 1b was 2316.8 mg/kg which was lower than valsartan (LD50 = 307.50 mg/kg) but higher than losartan (LD50 = 2248 mg/kg). So they could be considered as novel anti-hypertension candidates and deserved for further investigation.
- Nie, Yong-Yan,Da, Ya-Jing,Zheng, Hao,Yang, Xiao-Xia,Jia, Lin,Wen, Cai-Hong,Liang, Li-Sha,Tian, Juan,Chen, Zhi-Long
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experimental part
p. 2747 - 2761
(2012/05/20)
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- Design, synthesis, and applications of potential substitutes of t-Bu-phosphinooxazoline in Pd-catalyzed asymmetric transformations and their use for the improvement of the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates
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The design, synthesis, and applications of potential substitutes of t-Bu-PHOX in asymmetric catalysis is reported. The design relies on the incorporation of geminal substituents at C5 in combination with a substituent at C4 other than t-butyl (i-Pr, i-Bu, or s-Bu). Most of these new members of the PHOX ligand family behave similarly in terms of stereoinduction to t-Bu-PHOX in three palladium-catalyzed asymmetric transformations. Electronically modified ligands were also prepared and used to improve the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates.
- Belanger, Etienne,Pouliot, Marie-France,Courtemanche, Marc-Andre,Paquin, Jean-Francois
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scheme or table
p. 317 - 331
(2012/02/15)
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- Design, synthesis and biological evaluation of novel amino acid ureido derivatives as aminopeptidase N/CD13 inhibitors
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A series of amino acid ureido derivatives as aminopeptidase N (APN/CD13) inhibitors were synthesized and evaluated for their APN inhibitory activities and anti-cancer effects. The results showed that most of these amino acid ureido derivatives exhibited good inhibition against APN, several of which were better than Bestatin. The most active compound 12j (IC50 = 1.1 μM, compared with Bestatin IC50 = 8.1 μM) not only possessed much better APN inhibitory activity and anti-proliferation effect on cancer cells, but also exhibited significant block effect of human cancer cell invasion compared with the positive control, Bestatin. These amino acid ureido derivatives could be possibly developed as new APN inhibitors for cancer chemotherapy in the future.
- Su, Li,Jia, Yuping,Zhang, Lei,Xu, Yingying,Fang, Hao,Xu, Wenfang
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scheme or table
p. 3807 - 3815
(2012/08/27)
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- Synthesis of some n-aryl α-Amino acids using diaryliodonium salts
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Bis[(3'-methoxycarbonyl)phenyl]iodonium bromide (4a), bis (4'-methoxyphenyl)iodonium iodide (4b) and bis (4'-acetamidophenyl)iodonium iodide (4c) were employed for the first time in the arylation of α-amino acid methyl esters. Yields of the synthesised products 5, 6 and 7 were good to high. These were then hydrolyzed to the corresponding N-aryl α-amino acids 8 and 9. The chiral integrity of the amino acids was maintained throughout the reaction sequence as confirmed by the synthesis of chiral tripeptide 10 and dipeptides 11. The structures of the new compounds were confirmed by IR, 1H and 13C NMR in addition to CHN microanalysis or high resolution mass spectrometry.
- Mckerrow, Jason D.,Al-Rawi, Jasim M.,Brooks, Peter
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body text
p. 1227 - 1236
(2012/09/22)
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- Syntheses of novel chiral calix[4]crown: Lariat calix[4]-1,3-aza-crowns with chiral amino acid groups as branched chains
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The first examples of lariat calix[4]-1,3-aza-crowns with chiral amino acid groups as branched chains (5a and 5b) were designed and synthesized via a 1+1 addition reaction of calix[4]-1,3-substituted benzaldehyde derivative (4) and amino acid hydrazide derivatives (3a and 3b) in yields of 70% and 75%, respectively. The preliminary extraction experiments suggested that hosts 5a and 5b possessed good complexation abilities for-amino acids.
- Yang, Fafu,Liu, Zhiqiang,Huang, Zhisheng,Guo, Hongyu,Hong, Biqiong
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scheme or table
p. 3485 - 3490
(2011/10/02)
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- Synthesis of novel chiral calix[4]crown: Lariat calix[4]-1,3-aza-crown with chiral amino acid group as branched chain
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The novel lariat calix[4]-1,3-aza-crowns with chiral amino acids groups as branched chain (5a) and (5b) were synthesized via "1+1" addition of calix[4]-1,3-substituted benzaldehyde derivative (4) and amino acids hydrazide derivatives (3a) and (3b) in yields of 70% and 75%, respectively.
- Yang, Fafu,Hong, Biqiong,Guo, Hongyu,Huang, Zhisheng,Zhang, Xiaoyi
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scheme or table
p. 358 - 360
(2012/05/31)
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- A facile and efficient approach to the synthesis of novel chiral molecular tweezers based on deoxycholic acid under microwave irradiation
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A rapid, safe and efficient method for the synthesis of novel molecular tweezers with one chiral arm based on deoxycholic acid was reported. Ten new molecular tweezers have been synthesized in good yields. The structures of these new molecular tweezers were characterized by 1H NMR, IR, MS spectra and elemental analysis. These chiral molecular tweezers showed good enantioselectivity for D-amino acid methyl esters.
- Chen, Yu,Zhao, Zhi-Gang,Liu, Xing-Li,Shi, Zhi-Chuan
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body text
p. 210 - 215
(2012/04/04)
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- Hydantoin-free synthesis of peptide ester isocyanates, isothiocyanates, and dipeptidyl ureas: The application of zinc dust in a carbonylation procedure without base
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Non-Schotten-Baumann conditions are described for the hydantoin-free synthesis of peptide ester isocyanates using activated zinc dust as a non-basic HCl scavenger. Also, the procedure gives no N-acylated products in the case of the conversion of amino acid and peptide amides into isocyanates. Georg Thieme Verlag Stuttgart · New York.
- Narendra,Vishwanatha,Sureshbabu, Vommina V.
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body text
p. 3247 - 3254
(2011/11/30)
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- Use of diphenyliodonium bromide in the synthesis of some N-phenyl-amino acids
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The N-phenyl methyl esters 4 of glycine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, proline, serine, threonine, tyrosine, aspartic acid, and glutamic acid have been synthesized in good to excellent yields using diphenyliodonium bromide, AgNO3, and a catalytic amount of CuBr starting from the relevant amino acid ester. The chiral integrity of the amino acids 5 was maintained during these reactions, which were confirmed by the synthesis of dipeptide for each N-phenyl amino acid. The structures of the new compounds were confirmed by the analysis of their IR, 1H, and 13C NMR spectra in addition to CHN microanalysis or high-resolution mass spectrometry for the new N-phenyl amino acids 5 and the esters 4.
- McKerrow, Jason D.,Al-Rawi, Jasim M. A.,Brooks, Peter
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experimental part
p. 1161 - 1179
(2010/04/28)
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- Synthesis, characterization and biological activity of novel (5-RS,6-S)-5-sec-butyl-3-(1-substituted-amino)ethylidene-1H-pyrrolidine-2, 4-diones
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A series of novel tetramic acid derivatives, 5-sec-butyl-3-(1- substitutedamino)ethylidene-1H-pyrrolidine-2,4-diones 5a-y were synthesized by reaction with aryl amines or alkyl amines under reflux. Each title compound was formed as (5S,6S) and (5R,6S) C-5 epimers, and the structure of 5l was proved by X-ray diffraction analysis. Our preliminary bioassay results show the title compounds to exhibit some herbicidal activities and better antifungal activities than the leading compound tenuazonic acid at 100 mg L -1 in vitro, and the compound 5u displayed excellent herbicidal activity and antifungal activity.
- Wang, Xian-Feng,Si, Teng-Fei,Li, Qing-Bin,Zhu, Zhao-Yong,Zhu, Xian-Jie,Qiang, Sheng,Yang, Chun-Long
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scheme or table
p. 31 - 48
(2010/10/21)
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- Facile synthesis of β-amino disulfides, cystines, and their direct incorporation into peptides
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Herein, we report a simple and efficient methodology for the synthesis of β-amino disulfides by regioselective ring opening of sulfamidates with benzyltriethylammonium tetrathiomolybdate [BnNEt3] 2MoS4. Stability and reactivity of different protecting groups under the reaction conditions have been discussed. This methodology has also been extended to serine and threonine derived sulfamidates to furnish cystine and 3,3′-dimethyl cystine derivatives. Georg Thieme Verlag.
- Nasir Baig,Kanimozhi, Catherine K.,Sudhir, V. Sai,Chandrasekaran, Srinivasan
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scheme or table
p. 1227 - 1232
(2009/09/06)
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- Synthesis and evaluation of a novel series of heterocyclic oleanolic acid derivatives with anti-osteoclast formation activity
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Oleanolic acid with anti-bone resorption effect was an active component discovered in a medicinal plant of Achyranthes bidentata. A series of heterocyclic derivatives of oleanolic acid including indole, pyrazine, quinoxaline, quinoline moieties and their natural amino acid amides were synthesized. Their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) and cytotoxicity of the selected derivatives were evaluated. Among the derivatives, compounds 2a and 8a displayed quite a potent activity even at 200 nM. The structure-activity relationships of the derivatives were also discussed.
- Li, Jun-Feng,Zhao, Yu,Cai, Min-Min,Li, Xiao-Fei,Li, Jian-Xin
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scheme or table
p. 2796 - 2806
(2009/10/10)
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- Synthesis and utilization of trifluoromethylated amino alcohol ligands for the enantioselective Reformatsky reaction and addition of diethylzinc to N-(diphenylphosphinoyl)imine
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A series of trifluoromethylated amino alcohol ligands, which had been designed and conveniently prepared, were successfully applied in the enantioselective Reformatsky reaction and addition of diethylzinc to N-(diphenylphosphinoyl)imine, respectively. The influence of the substituents on C-3 position and the amino moiety on the enantioselectivity has been carefully investigated. In the best cases, ligand 1b exhibited good selectivity for the enantioselective Reformatsky reaction in 86% ee and ligand 12d provided excellent enantioselectivity in the addition of diethylzinc to N-(diphenylphosphinoyl)imine with 95% ee.
- Xu, Xiu-Hua,Qiu, Xiao-Long,Qing, Feng-Ling
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p. 7353 - 7361
(2008/12/20)
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- Application of phosphoramidate ProTide technology significantly improves antiviral potency of carbocyclic adenosine derivatives
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We report the application of phosphoramidate pronucleotide (ProTide) technology to the antiviral agent carbocyclic L-d4A (L-Cd4A). The phenyl methyl alaninyl parent ProTide of L-Cd4A was prepared by Grignard-mediated phosphorochloridate reaction and resulted in a compound with significantly improved anti-HIV (2600-fold) and HBV activity. We describe modifications of the aryl, ester, and amino acid regions of the ProTide and how these changes affect antiviral activity and metabolic stability. Separate and distinct SARs were noted for HIV and HBV. Additionally, ProTides were prepared from the D-nucleoside D-Cd4A and the dideoxy analogues L-CddA and D-CddA. These compounds showed more modest potency improvements over the parent drug. In conclusion, the ProTide approach is highly successful when applied to L-Cd4A with potency improvements in vitro as high as 9000-fold against HIV. With a view to preclinical candidate selection we carried out metabolic stability studies using cynomolgus monkey liver and intestinal S9 fractions.
- McGuigan, Christopher,Hassan-Abdallah, Alshaimaa,Srinivasan, Sheila,Wang, Yikang,Siddiqui, Adam,Daluge, Susan M.,Gudmundsson, Kristjan S.,Zhou, Huiqiang,McLean, Ed W.,Peckham, Jennifer P.,Burnette, Thimysta C.,Marr, Harry,Hazen, Richard,Condreay, Lynn D.,Johnson, Lance,Balzarini, Jan
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p. 7215 - 7226
(2007/10/03)
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- Antimicrobial metabolites produced by an intertidal Acremonium furcatum
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In a screening for antimicrobial metabolites, amides of d-allo- and l-isoleucine derivatives were isolated from the culture of a marine strain of Acremonium furcatum. Structural elucidation of these compounds was performed by analysis of spectroscopic data and confirmed by synthesis. All of the compounds, natural and synthetic intermediates, were bioassayed against bacteria and phytopathogenic fungi, with many showing remarkable antifungal activities.
- Gallardo, Gabriela L.,Butler, Matias,Gallo, Mariana L.,Rodriguez, M. Alejandra,Eberlin, Marcos N.,Cabrera, Gabriela M.
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p. 2403 - 2410
(2007/10/03)
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- Synthesis and activity of oleanolic acid derivatives, a novel class of inhibitors of osteoclast formation
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Two series of oleanolic acid derivatives were synthesized and their inhibitory activity on the formation of osteoclast-like multinucleated cells (OCLs) induced by 1α,25-dihydroxy vitamin D3 was evaluated in a co-culture assay system. The structure-activity relationships, together with electronic structure based on the frontier molecular orbitals, for example, HOMO and LUMO, related to different amino acid substituents were studied. Derivatives with proline or phenylalanine showed a tendency to enhance the inhibitory activity.
- Zhang, Yuan,Li, Jian-Xin,Zhao, Jianwei,Wang, Shao-Zhong,Pan, Yi,Tanaka, Ken,Kadota, Shigetoshi
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p. 1629 - 1632
(2007/10/03)
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- Synthesis of erythro-α-Amino β-hydroxy Carboxylic Acid Esters by Diastereoselective Photocycloaddition of 5-Methoxyoxazoles with Aldehydes
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A new photoaldol route to α-amino-β-hydroxy carboxylic acid esters is initiated by the photocycloaddition of aromatic or aliphatic aldehydes to 5-methoxyoxazoles. The 4-unsubstituted 5-methyloxazole 1 gave the cycloadducts 8a-f in high yields and excellent exo-diastereoselectivities. Hydrolysis of 8a-f gives the N-acetyl α-amino-β-hydroxy esters 9a-f, which could be subsequently converted into the corresponding Z-didehydro α-amino acids 10a-f. Quartenary α-amino-β-hydroxy esters 12, 14, 16, 18, and 20, which are stable against dehydration, were obtained from the 4-alkylated 5-methoxyoxazoles 2-6, in most cases highly erythro-selective due to the high degree of stereocontrol (exo) at the photocycloaddition (to give 11, 13, 15, 17, and 19) level. The relative configurations of the N-acetyl α-amino-β-hydroxy esters were determined by NMR spectroscopy and comparison with chiral pool-derived compounds as well as by X-ray structure determination of the ester 23, formed by hydrolysis of the cycloadduct 22, derived from photocycloaddition of propionaldehyde to the isoleucine-derived oxazole 21.
- Griesbeck, Axel G.,Bondock, Samir,Lex, Johann
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p. 9899 - 9906
(2007/10/03)
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- A convenient synthesis of chiral dioxocyclens and application as chiral solvating agents
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This paper reports a very short and efficient synthesis of chiral dioxocyclens starting from natural amino acids. NMR experiments were undertaken to assess the chiral recognition properties of these chiral macrocycles. The NMR spectra of mandelic acid or its derivatives in the presence and absence of the chiral dioxocyclens showed that these macrocycles have different enantiomeric discriminating ability. It was revealed that this type of dioxocyclen may be promising hosts for chiral discrimination.
- Yuan, Quan,Fu, Enqin,Wu, Xiaojun,Fang, Maohai,Xue, Peng,Wu, Chengtai,Chen, Jiahua
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p. 3935 - 3937
(2007/10/03)
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- Enantioselective reduction of aromatic ketones catalysed by chiral ruthenium(II) complexes
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The catalytic enantioselective reduction of aromatic ketones in 2- propanol is carried out by using ruthenium(II) complexes prepared from [Ru(p- cymene)Cl2]2 and a variety of chiral diamines and β-aminoalcohols derived from α-amino acids. Good conversions (>99%) and enantioselectivities (=96%) are observed under mild reaction conditions. (C) 2000 Elsevier Science Ltd.
- Aitali,Allaoud,Karim,Meliet,Mortreux
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p. 1367 - 1374
(2007/10/03)
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- A simple and efficient procedure for the preparation of chiral 2-oxazolidinones from α-amino acids
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A modified procedure for the title transformation is described which avoids: (i) a potentially hazardous borane reduction step, and (ii) the intermediacy of water soluble amino alcohols.
- Lewis,McKillop,Taylor,Watson
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p. 561 - 568
(2007/10/02)
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- DIMERISATION DE DIENES CONJUGUES A L'AIDE DE COMPLEXES DU NICKEL EN PRESENCE DE LIGANDS DE TYPE AMINOPHOSPHINITE ETUDE D'OPTIMISATION
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New chiral aminophosphinite ligands are readily prepared and their behaviour as homogeneous catalysts was investigated in the linear dimerization of butadiene and isoprene.This latter reaction has been optimised using experimental research methodology, leading to a conversion rate above 50percent.
- Masotti, Henriette,Pfeiffer, Gilbert,Siv, Chhan,Courbis, Pierre,Sergent, Michelle,Phan TAN LUU, Roger
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- HETEROCYCLES FROM NITRILE IMINES. PART IV. CHIRAL 4,5-DIHYDRO-1,2,4-TRIAZIN-6-ONES
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The reaction of nitrile imines (II) with α-amino esters (III) proceeds with no detectable racemization and constitutes a convenient synthetic route to 4,5-dihydro-1,2,4-triazin-6-ones (IV).Permangamate oxidation of heterocycles (IV) affords the corresponding 1,2,4-triazin-6-ones (V).The reaction of (II) with β-amino esters gives the respective acyclic amidrazone adducts (VI).
- El-Abadelah, Mustafa M.,Hussein, Ahmad Q.,Thaher, Bassam A.
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p. 1879 - 1895
(2007/10/02)
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- Peptide Side-Arm Derivatives of Lariat Ethers and Bibracchial Lariat Ethers: Syntheses, Cation Binding Properties, and Solid State Structural Data
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Aza-18-crown-6 and 4,13-diaza-18-crown-6 derivatives having one or two side arms have been prepared.The side arms are of the form >N-Gly-AA-OMe, where "AA" is an amino acid.The 18-membered ring compounds were prepared by alkylation of aza-18-crown-6 as follows: Gly-Gly-OMe (14, 57percent, mp 42-43 deg C); Gly-Ile-OMe (15, 50percent); Gly-Val-OMe (16, 56percent).Two-armed compounds were obtained by alkylation of 4,13-diaza-18-crown-6 as follows: Gly-Gly-OMe (18, 58percent, mp 118-119 deg C); Gly-Ala-OMe (19, 50percent, mp 62-63 deg C); Gly-Phe-OMe (20, 65percent, oil); Gly-Leu-OMe (21, 51percent, mp 72-73 deg C); Gly-Ile-OMe (22, 60percent, oil); Gly-Val-OMe (23, 59percent, oil).Sodium iodide complexes of 18, 19, and 20 were isolated.Solid state structural data are reported for 18 and its sodium complex, as well as its potassium complex that was reported in preliminary form (ref 9f).Compound 18 crystallizes in the triclinic space group P1 with cell constants a = 9.0210 (8), b= 10.4768 (15), and c = 15.357 (2) Angstroem, α = 87.457 (12) deg, β = 87.119 (10) deg, γ = 68.042 (9) deg, and Z = 2 for Dc = 1.286 g cm-3.Least-squares refinement based on 4034 observed reflections led to a final conventional R value of 0.041.The sodium iodide complex of 18 crystallizes in the monoclinic space group P21/c with cell constants a = 9.732 (3), b = 17.710 (2), and c = 38.848 (3) Angstroem, β = 96.99 (2) deg, and Z = 8 for Dc = 1.430 g cm-3.Least-squares refinement based on 5512 observed reflection led to a final conventional R value of 0.041.The potassium iodide complex of 18 crystallizes in the monoclinic space group C2/c with cell constans a = 15.656 (4), b = 14.752 (3), and c = 26.784 (3) Angstroem, β = 90.01 (2), and Z = 8 for Dc = 1.474 g cm-3.Least-squares refinement based on 2595 observed reflections led to a final conventional R value of 0.035.There are two crystallographically independent molecules in each of the three crystal structures.The sodium and potassium complexes are compared to other BiBLE complexes and to cryptates.Cation binding affinities for these compounds have been assessed in anhydrous methanol and are reported here for Na+ and K+ cations.
- White, Banita D.,Mallen, Jesus,Arnold, Kristin A.,Fronczek, Frank R.,Gandour, Richard D.,et al.
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p. 937 - 947
(2007/10/02)
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- RELATIONSHIPS BETWEEN THE STRUCTURE AND THE PHYTOTOXICITY OF THE FUNGAL TOXIN TENUAZONIC ACID
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Tenuazonic acid (3-acetyl 5-sec-butyl pyrrolidine-2,4-dione) is a metabolite produced by the fungal pathogen of rice Pyricularia oryzae.It inhibits growth of plants by interferring with protein synthesis at the ribosome level.We have synthesized analogues of tenuazonic acid with various substituents at C-3 and C-5.Substituents at C-5 other than sec-butyl or n-propyl, decrease the phytotoxicity of the analogues.But substitutions at C-3 abolish the toxicity.Thus, tenuazonic acid seems to have the optimal structure for phytotoxicity.Tenuazonic acid induces rice leaf defence reactions (browning) of reactive varieties which are resistant to P. oryzae.Some of the analogues synthesized have a low level of phytotoxicity and are able to induce this leaf browning of the reactive rice varieties.Thus different structural features are required for phytotoxicity and for leaf browning.Key Word Index - Tenuazonic acid; pyrrolidine-2,4-diones; rice; phytotoxicity; Pyricularia oryzae; structure-activity.
- Lebrun, M. H.,Nicolas, L.,Boutar, M.,Gaudemer, F.,Ranomenjanahary, S.,Gaudemer, A.
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- SYNTHESE DE LIGANDS DE TYPE AMINO-DIPHOSPHINITES; ETUDE EN RMN 13 C ET 31 P. APPLICATION A LA DIMERISATION DU BUTADIENE PAR LES COMPLEXES DU NICKEL
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The new chiral aminodiphosphinite ligands are readily prepared from chiral amino acids.These compounds were characterized by 13 C and 31 P NMR spectroscopy and their behaviour as homogeneous catalysts was investigated in the linear dimerization of butadiene.
- Bendayan, Andree,Masotti, Henriette,Peiffer, Gilbert,Siv, Chhan,Faure, Robert
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p. 289 - 298
(2007/10/02)
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- SYNTHESE D'AMINOPHOSPHINEPHOSPHINITES CHIRAUX. UTILISATION EN REDUCTION ASYMETRIQUE CATALYTIQUE
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The chiral aminophosphinephosphinites ligands (AMPP) are directly synthesized from natural amino alcohols or by reduction of formyl esters of α-amino acids and PPh2Cl. Their cationic rhodium complexes have been found to be excellent catalysts for enantioselective hydrogenation of dehydroamino acids (ee ca. 86percent, yield ca. 100percent) for example.Asymmetric reduction of ketones can also be performed with the new alkyl AMPP* modified rhodium catalyst (ee 50percent).
- Karim, A.,Mortreux, A.,Petit, F.,Buono, G.,Pfeiffer, G.,Siv, C.
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- Inhibition of cell growth and [3H]-thymidine incorporation in human mammary carcinoma cell line MDA-MB 231 by PtCi2-complexes of 1.2-diaminoethanes derived from amino acids
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Substituted L-1.2-diaminoethanes were prepared from L-α-amino acids and used as ligand in the synthesis of platinum(II) complexes. The L-1.2-diaminoethane-dichloro-platinum(II) complexes were examined with respect to their cytostatic effect. As an in vitro test system the hormone independent human mammary carcinoma cell line MDA-MB 231 was used. All the examined complexes cause a strong inhibition of DNA synthesis in the tumor cells.
- Brunner,Schmidt,Unger,Schonenberger
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p. 509 - 512
(2007/10/02)
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