- Silver ion-induced chiral enhancement by argentivorous molecules
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Optically active tetra-armed cyclens with an asymmetric chiral centre in the cyclen moiety were synthesized and were shown to enhance chirality and control of enantiomers on complexation with Ag+. Binding studies of the Ag+ complex demonstrated that Ag+ preferentially interacts with electron-rich substituents over other aromatic substituents.
- Lee, Eunji,Hosoi, Yasuhiro,Temma, Honoka,Ju, Huiyeong,Ikeda, Mari,Kuwahara, Shunsuke,Habata, Yoichi
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- TRANSFORMATION OF GLYCYRRHIZIC ACID. VII. SYNTHESIS OF TRITERPENE GLYCOPEPTIDES CONTAINING ALKYL ESTERS OF L-AMINO ACIDS
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The synthesis has been effected by the activated N-hydroxy succinimide ester method of new triterpene glycopeptides derived from glycyrrhizic acid, containing fragments of alkyl (ethyl, propyl, butyl) esters of L-amino acids.
- Baltina, L.A.,Ryzhova, S.A.,Vasil'eva, E.V.,Tolstikov, G.A.
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Read Online
- Synthesis of 2-(5-Hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone
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2-(5-Hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone was synthesized in six steps with a 17.0% overall yield, starting from L-alanine. The synthetic route involved the Clauson-Kaas reaction, Vilsmeier reaction, and transesterification. The transesterification was the key step in the formation of the target compound.
- Bu, Xiaolin,Li, Yueqing,Liu, Jihong,Zeng, Debin,Zhao, Weijie
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- Characterization and cytotoxicity evaluation of biocompatible amino acid esters used to convert salicylic acid into ionic liquids
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The technological utility of active pharmaceutical ingredients (APIs) is greatly enhanced when they are transformed into ionic liquids (ILs). API-ILs have better solubility, thermal stability, and the efficacy in topical delivery than solid or crystalline drugs. However, toxicological issue of API-ILs is the main challenge for their application in drug delivery. To address this issue, 11 amino acid esters (AAEs) were synthesized and investigated as biocompatible counter cations for the poorly water-soluble drug salicylic acid (Sal) to form Sal-ILs. The AAEs were characterized using 1H and 13C NMR, FTIR, elemental, and thermogravimetric analyses. The cytotoxicities of the AAE cations, Sal-ILs, and free Sal were investigated using mammalian cell lines (L929 and HeLa). The toxicities of the AAE cations greatly increased with inclusion of long alkyl chains, sulfur, and aromatic rings in the side groups of the cations. Ethyl esters of alanine, aspartic acid, and proline were selected as a low cytotoxic AAE. The cytotoxicities of the Sal-ILs drastically increased compared with the AAEs on incorporation of Sal into the cations, and were comparable to that of free Sal. Interestingly, the water miscibilities of the Sal-ILs were higher than that of free Sal, and the Sal-ILs were miscible with water at any ratio. A skin permeation study showed that the Sal-ILs penetrated through skin faster than the Sal sodium salt. These results suggest that AAEs could be used in biomedical applications to eliminate the use of traditional toxic solvents for transdermal delivery of poorly water-soluble drugs.
- Moshikur, Rahman Md.,Chowdhury, Md. Raihan,Wakabayashi, Rie,Tahara, Yoshiro,Moniruzzaman, Muhammad,Goto, Masahiro
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- Evidence for the optical signalling of changes in bicarbonate concentration within the mitochondrial region of living cells
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Image and spectral intensity from bicarbonate-selective europium(iii) probes localised in the mitochondria of cells is modulated reversibly by variation of external pCO2, and is suppressed by addition of the carbonic anhydrase inhibitor, acetazolomide.
- Smith, David G.,Law, Ga-Lai,Murray, Benjamin S.,Pal, Robert,Parker, David,Wong, Ka-Leung
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Read Online
- Asymmetric Synthesis of N-Substituted α-Amino Esters from α-Ketoesters via Imine Reductase-Catalyzed Reductive Amination
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N-Substituted α-amino esters are widely used as chiral intermediates in a range of pharmaceuticals. Here we report the enantioselective biocatalyic synthesis of N-substituted α-amino esters through the direct reductive coupling of α-ketoesters and amines employing sequence diverse metagenomic imine reductases (IREDs). Both enantiomers of N-substituted α-amino esters were obtained with high conversion and excellent enantioselectivity under mild reaction conditions. In addition >20 different preparative scale transformations were performed highlighting the scalability of this system.
- Yao, Peiyuan,Marshall, James R.,Xu, Zefei,Lim, Jesmine,Charnock, Simon J.,Zhu, Dunming,Turner, Nicholas J.
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supporting information
p. 8717 - 8721
(2021/03/16)
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- Novel naphthylamide derivatives as dual-target antifungal inhibitors: Design, synthesis and biological evaluation
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Fungal infections have become a serious medical problem due to the high infection rate and the frequent emergence of drug resistance. Squalene epoxidase (SE) and 14α-demethylase (CYP51) are considered as the important antifungal targets, they can show the synergistic effect on antifungal therapy. In the study, a series of active fragments were screened through the method of De Novo Link, and these active fragments with the higher Ludi_Scores were selected, which can show the obvious binding ability with the dual targets (SE, CYP51). Subsequently, three series of target compounds with naphthyl amide scaffolds were constructed by connecting these core fragments, and their structures were synthesized. Most of compounds showed the antifungal activity in the treatment of pathogenic fungi. It was worth noting that compounds 10b-5 and 17a-2 with the excellent broad-spectrum antifungal properties also exhibited the obvious antifungal effects against drug-resistant fungi. Preliminary mechanism study has proved these target compounds can block the biosynthesis of ergosterol by inhibiting the activity of dual targets (SE, CYP51). Furthermore, target compounds 10–5 and 17a-2 with low toxicity side effects also demonstrated the excellent pharmacological effects in vivo. The molecular docking and ADMET prediction were performed, which can guide the optimization of subsequent lead compounds.
- An, Yunfei,Dong, Yue,Liu, Min,Han, Jun,Zhao, Liyu,Sun, Bin
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- Design, synthesis and biological evaluation of novel 2-(5-aryl-1H-imidazol-1-yl) derivatives as potential inhibitors of the HIV-1 Vpu and host BST-2 protein interaction
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Novel ethyl 2-(5-aryl-1H-imidazol-1-yl)-acetates 17 and propionates 18, together with their acetic acid 19 and acetohydrazide 20 derivatives, were designed and synthesized using TosMIC chemistry. Biological evaluation of these newly synthesized scaffolds in the HIV-1 Vpu- Host BST-2 ELISA assay identified seven hits (17a, 17b, 17c, 17g, 18a, 20f and 20g) with greater than 50% inhibitory activity. These hits were validated in the HIV-1 Vpu- Host BST-2 AlphaScreen and six of the seven compounds were found to have comparable percentage inhibitory activities to those of the ELISA assay. Compounds 17b and 20g, with consistent percentage inhibitory activities across the two assays, had IC50 values of 11.6 ± 1.1 μM and 17.6 ± 0.9 μM in a dose response AlphaScreen assay. In a cell-based HIV-1 antiviral assay, compound 17b exhibited an EC50 = 6.3 ± 0.7 μM at non-toxic concentrations (CC50 = 184.5 ± 0.8 μM), whereas compound 20g displayed antiviral activity roughly equivalent to its toxicity (CC50 = 159.5 ± 0.9 μM). This data suggests that compound 17b, active in both cell-based and biochemical assays, provides a good starting point for the design of possible lead compounds for prevention of HIV-1 Vpu and host BST-2 protein binding in new anti-HIV therapeutics.
- Bode, Moira L.,Coyanis, E. Mabel,Mosebi, Salerwe,Njengele, Zikhona,Rashamuse, Thompho J.,Sayed, Yasien
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- Potent arylamide derivatives as dual-target antifungal agents: Design, synthesis, biological evaluation, and molecular docking studies
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Fungal infections have become a serious medical problem due to the high infection rate and the frequent emergence of drug resistance. Ergosterol is an important structural component of the fungal cell membrane, its synthetases (squalene epoxidase (SE) and 14α-demethylase (CYP51)) are considered as the key points to block the ergosterol synthesis. In this study, we designed a series of dual-target arylamides derivatives based on the analysis of active sites (SE, CYP51). Subsequently, these target compounds were synthesized, and their antifungal activity was evaluated. Most of compounds demonstrate the potent antifungal activity against multiple Candida spp. and A. fum. In particular, the antifungal activities of compounds 10b and 11c are not only superior to positive control drugs, but also have significant inhibitory effects on drug-resistant fungi (C.alb. Strain100, C.alb. Strain103). Therefore, their action mechanism was further studied. Cellular uptake and electron microscopy observation showed that target compounds were able to enter fungal cytoplasmic region through free diffusion, and destroyed cell membrane structure. At the same time, preliminary mechanisms have demonstrated that they can affect the synthesis of ergosterol by inhibiting the activity of dual targets. It is worth noting that they also can exhibit excellent antifungal activity and low toxic side effects in vivo. Their ADMET properties and binding models were established will be useful for further lead optimization.
- An, Yunfei,Dong, Yue,Han, Jun,Liu, Min,Liu, Xinyong,Sun, Bin
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- Construction of antifungal dual-target (SE, CYP51) pharmacophore models and the discovery of novel antifungal inhibitors
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Fungal infections and drug-resistance are rapidly increasing with the deterioration of the external environment. Squalene cyclooxygenase (SE) and 14α-demethylase (CYP51) are considered to be important antifungal targets, and the corresponding pharmacophore models can be used to design and guide the discovery of novel inhibitors. Therefore, the common feature pharmacophore model (SE inhibitor) and structure-based pharmacophore model (CYP51 receptor) were constructed using different methods in this study. Then, appropriate organic fragments were selected and superimposed onto the pharmacophore features, and compounds 5, 6 and 8 were designed and produced by linking these organic fragments. It is noteworthy that compound 8 can simultaneously match the features of both the SE and CYP51 pharmacophores. Further analysis found that these compounds exhibit a potent antifungal activity. Preliminary mechanistic studies revealed that compound 8 could undergo dual-target inhibition (SE and CYP51) of Candida albicans. This study proved the rationale of pharmacophore models (SE and CYP51), which can guide the design and discovery of new antifungal inhibitors.
- Dong, Yue,Liu, Min,Wang, Jian,Ding, Zhuang,Sun, Bin
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p. 26302 - 26314
(2019/09/09)
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- Discovery of 2'-α-C-Methyl-2'-β-C-fluorouridine Phosphoramidate Prodrugs as Inhibitors of Hepatitis C Virus
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2′-α-C-Methyl-2′-β-C-fluorouridine and its phosphoramidate prodrugs were synthesized and evaluated for their inhibitory activity against HCV. The structure?activity relationship analysis of the phosphoramidate moiety found that 17m, 17q, and 17r exhibit potent activities against HCV, with EC50 values of 1.82 ± 0.19, 0.88 ± 0.12, and 2.24 ± 0.22 μM, respectively. The docking study revealed that the recognition of the 2′-β-F by Arg158, 3′-OH by N291, and the Watson?Crick pairing with the template allowed 23 to form the in-line conformation necessary for its incorporation into the viral RNA chain.
- Zeng, Debin,Zhang, Rui,Nie, Quandeng,Cao, Lin,Shang, Luqing,Yin, Zheng
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supporting information
p. 1197 - 1201
(2016/12/18)
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- 4'-VINYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF RESPIRATORY SYNCYTIAL VIRUS RNA REPLICATION
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The application discloses compounds of Formula I wherein the variable substituents are as defined herein. The compounds of Formula I and pharmaceutical compositions comprising compounds of Formula I are useful for the treatment of diseases mediated by RSV.
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Paragraph 0222; 0223; 0224
(2016/10/04)
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- Safe and Selective Nitro Group Reductions Catalyzed by Sustainable and Recyclable Fe/ppm Pd Nanoparticles in Water at Room Temperature
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As a result of a unique synergy between ligand-free Fe/ppm Pd nanoparticles and PEG-containing designer surfactants, a facile and selective reduction of nitro-containing aromatics and heteroaromatics can be effected in water at room temperature in the presence of NaBH4. This new nanotechnology involves low catalyst loadings, is highly chemoselective, and tolerates a wide variety of functional groups. The process, which includes recycling of the entire aqueous medium, offers a general, environmentally responsible, and notably safe approach to highly valued reductions of nitro-containing compounds.
- Feng, Jie,Handa, Sachin,Gallou, Fabrice,Lipshutz, Bruce H.
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supporting information
p. 8979 - 8983
(2016/07/26)
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- Argentivorous molecules bearing three aromatic side arms: Synthesis of triple-armed cyclens and their complexing property towards Ag+
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Triple-armed cyclens bearing three aromatic side-arms were prepared in three steps from (3R,5S)-3,5-dimethyl-1,4,7,10-tetraazacyclododecane-2,6-dione, and the Ag+-ion-induced 1H NMR and UV-vis spectral changes and X-ray structures suggested that the aromatic side-arms cover the Ag+ incorporated into the ligand cavities like an insectivorous plant (Venus flytrap).
- Habata, Yoichi,Kizaki, Juli,Hosoi, Yasuhiro,Ikeda, Mari,Kuwahara, Shunsuke
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p. 1170 - 1177
(2015/02/02)
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- Synthesis of novel nucleoside analogue phosphorothioamidate prodrugs and in vitro anticancer evaluation against RKO human colon carcinoma cells
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Novel phosphorothioamidates of pyrimidine nucleoside analogues have been prepared and evaluated in vitro against RKO human colon cancer cell by the MTT cytotoxicity assay. The parent nucleoside analogues were inactive in this assay, while the phosphorothioamidate prodrugs were active at low uM levels in some cases. The O-isopropyl phosphorothioamidate of 2 ′,3 ′-O- isopropylidene-uridine containing the L-phenylalanine ethyl ester 6f was the most active at 148 uM, a 10-fold enhancement in anticancer activity compared with the parent nucleoside 2 with no increase in cytotoxicity.
- Liu, Wei,Zhang, Lin,Zhou, Honggang,Yang, Cheng,Miao, Zhiwei,Zhao, Yufen
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p. 161 - 173
(2013/06/04)
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- Asymmetric construction of quaternary stereocenters: Synthesis of enantiopure amino acid-based tricyclic α,β-enones through an ipso-Friedel-Crafts/Michael addition cascade
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An efficient reaction of the (2R,1′S)- or (2S,1′S)-N,N-bis(p- methoxybenzyl)-2-(1-aminoalkyl)epoxides, derived from α-amino acids, with boron trifluoride-phosphoric acid complex is described. This process affords highly elaborated enantiopure tricyclic α,β-enones in high yields, through an ipso-Friedel-Crafts/Michael addition cascade. Copyright
- Rodriguez-Solla, Humberto,Concellon, Carmen,Tuya, Paula,Garcia-Granda, Santiago,Diaz, M. Rosario
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experimental part
p. 295 - 300
(2012/04/04)
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- Antimicrobial toxicity studies of ionic liquids leading to a 'hit' MRSA selective antibacterial imidazolium salt
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Imidazolium salts can be classed as surfactants, detergents, ionic liquids, reagents, catalysts or solvents. A study of the toxicity and ecotoxicity of these salts yields valuable information for their use as pharmaceuticals as well as impact on the environment. Our approach to screen a series of chiral imidazolium salts for toxicity to bacteria and fungi, including clinical pathogen strains, has led to the identification of a 'hit' MRSA selective antimicrobial compound. Preliminary structure-activity-relationship (SAR) information (required position of l-phenylalanine and l-valine group) is also elucidated within this first generation of compounds. Conversely, most of the imidazolium salts were nontoxic (IC95 > 2 mM) to the 12 fungi strains and 8 bacteria strains screened, and we propose that they are suitable candidates for 'green chemistry' applications. Ecotoxicity studies (Biodegradation ISO 14593 'CO2 Headspace Test') of two bromide ionic liquids containing l-phenylalanine residues indicate that these ionic liquids passed the test (>60% in 28 days) and classed as readily biodegradable.
- Coleman, Deborah,Spulak, Marcel,Garcia, M. Teresa,Gathergood, Nicholas
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body text
p. 1350 - 1356
(2012/06/16)
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- A [3+3] cyclization strategy for asymmetric synthesis of alkyl substituted piperidine-2-ones using 1,2-cyclic sulfamidates: A formal synthesis of (S)-coniine from l-norvaline
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Regioselective ring-opening reactions of a set of representative 1,2-cyclic sulfamidates with lithium triethylorthopropiolate proceeded efficiently to deliver the corresponding δ-amino-α,β-unsaturated esters after acidic hydrolysis. Hydrogenation of the unsaturated esters and subsequent thermal cyclization afforded the related alkyl substituted piperidine-2-ones. This approach represents a novel [3+3] cyclization strategy for the asymmetric synthesis of alkyl substituted piperidin-2-ones. Efficiency of the cyclization process is illustrated by a formal asymmetric synthesis of (S)-coniine from l-norvaline.
- Karanfil, Abdullah,Balta, Berrin,Eskici, Mustafa
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p. 10218 - 10229,12
(2020/09/02)
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- Chiral 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimine analogues as novel potent neonicotinoids: Synthesis, insecticidal evaluation and molecular docking studies
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A new series of 1,5-disubstituted 1,3,5-hexahydrotriazine-2-N-nitroimines (4a-4x) were designed and synthesized as novel chiral neonicotinoid analogues. The single-crystal structure of 4n was further determined by X-ray diffraction, and its S configuration was confirmed. Preliminary bioassay showed that compound 4e, 4k, 4u, 4v exhibited excellent insecticidal activities at 100 mg/L, while 4k had >90% mortality at 10 mg/L, which suggested it could be used as a lead for future development. Modeling the inhibitor-nAChR complexes by molecular docking studies explained the structure-activity relationships observed in vitro, and revealed an intriguing molecular binding mode at the active site of nAChR, which raised the possibility that these analogues may arbitrate their insecticidal activity through a mechanism other than imidacloprid.
- Sun, Chuanwen,Zhu, Jun,Wang, Haifeng,Jin, Jia,Xing, Jiahua,Yang, Dingrong
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experimental part
p. 11 - 20
(2011/02/27)
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- Cyclic phosphoramidates as prodrugs of 2′-C-methylcytidine
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The currently approved treatment for hepatitis C virus infections is a combination of Ribavirin and pegylated Interferon. It leads to a sustained virologic response in approximately only half of the patients treated. For this reason there is an urgent need of new therapeutic agents. 2′-C-Methylcytidine is the first nucleoside inhibitor of the HCV NS5B polymerase that was efficacious in reducing the viral load in patients infected with HCV. The application of a monophosphate prodrug approach based on unprecedented cyclic phosphoramidates is reported. Our SAR studies led to compounds that are efficiently converted to the active triphosphate in human hepatocytes.
- Meppen, Malte,Pacini, Barbara,Bazzo, Renzo,Koch, Uwe,Leone, Joseph F.,Koeplinger, Kenneth A.,Rowley, Michael,Altamura, Sergio,Di Marco, Annalise,Fiore, Fabrizio,Giuliano, Claudio,Gonzalez-Paz, Odalys,Laufer, Ralph,Pucci, Vincenzo,Narjes, Frank,Gardelli, Cristina
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scheme or table
p. 3765 - 3770
(2009/12/24)
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- Self-assembled helical ribbon and tubes of alanine-based amphiphiles induced by two different formation mechanisms
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Three long chain alanine-based amphiphiles (1-3) possessing either a saturated long alkyl chain group or unsaturated groups as the self-assembling unit of a highly organized molecular architecture were synthesized. Their self-assembling properties were investigated using EF-TEM, SEM, CD, XRD, and FTIR. The d-form (1) and the l-form (2) enantiomers showed the opposite CD signals. Furthermore, electron micrographs of the self-assembled 1 and 2 exhibited right- and left-handed helical structures, respectively. The helical structures of amphiphiles 1 and 2 were developed into tubular structures by slow cooling. On the other hand, in the helical ribbon growth process, the helical pitch and ribbon width were changed in fast cooling process. The findings strongly imply that the helical ribbon growth of alanine-based amphiphiles can be induced by two different pathways. This mechanism, quite different from that observed for sugar- and cholesterol-based tubes, is a rare example for a tube formation process.
- Lee, Soo Jin,Kim, Eunjeong,Seo, Moo Lyong,Do, Youngkyu,Lee, Young-A.,Lee, Shim Sung,Jung, Jong Hwa,Kogiso, Masaki,Shimizu, Toshimi
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p. 1301 - 1308
(2008/09/17)
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- Diastereoselective Ugi reaction without chiral amines: the synthesis of chiral pyrroloketopiperazines
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The three-component Ugi reaction with chiral 2-(2-formyl-1H-pyrrol-1-yl)acetic acids prepared from natural l-aminoacids was investigated. The reaction opens a new route to chiral substituted pyrroloketopiperazines. One of the first examples of an asymmetric Ugi reaction without chiral amines is described. The reaction proceeds with moderate diastereoselectivity to give the target compounds in good yields. The scope and limitation of the approach are discussed.
- Nenajdenko, Valentine G.,Reznichenko, Alexander L.,Balenkova, Elizabeth S.
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p. 3031 - 3041
(2007/10/03)
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- Ultrasound accelerated synthesis of proteinogenic and α,α- dialkylamino acid ester salts
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A simple and efficient sonochemical esterification of proteinogenic as well as cyclic α,α-dialkyl amino acid methyl and ethyl ester hydrochloride salts employing thionyl chloride and alcohol has been reported. All the amino acid esters made have been obtained in good yield (94-98%) as pure compounds.
- Kantharaju,Babu, Vommina V. Suresh
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p. 1942 - 1944
(2007/10/03)
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- Interaction of VIVO, VVO2 and CuII with a peptide analogue SalGly-L-Ala
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The formation of complexes of a tripeptide analogue, salicylglycyl-L-alanine [HOC6H4C(O)NHCH2C(O)NHCH(CH3) -COOH, H2SalGly-L-Ala], was studied with CuII, VIVO and VVO2 in aqueous solution using pH-potentiometric and spectroscopic (UV/Vis, CD, EPR and 51V NMR) techniques. The results demonstrated the ambidentate character of the ligand. The metal ion-induced deprotonation and subsequent coordination of the two neighbouring amide groups was shown to occur in a cooperative way in the pH range 5-6. At pH ≈ 6.5 a complex with an (O-, 2 x CON-, COO-) binding set becomes predominant for both CuII, and VIVO. The affinity of the phenolate-O- for VIVO is high and the ligand is bound to this metal ion even at pH values greater than 10. Conversely, the affinity for VVO2 is significantly lower and no interaction between this metal oxo-ion and the ligand could be detected in the pH range 2-12. In contrast, with the dipeptide analogue H2SalGly, chelation involving the deprotonated amide-N-could be unambiguously detected. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Jakusch, Tamas,Doernyei, Agnes,Correia, Isabel,Rodrigues, Ligia M.,Toth, Gabor K.,Kiss, Tamas,Costa Pessoa, Joao,Marcao, Susana
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p. 2113 - 2122
(2007/10/03)
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- Stereocontrolled synthesis of β-lactams via staudinger reaction between phenoxyketenes and chiral imines
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Chiral Schiff bases derived from esters of valine and alanine have been shown to be useful intermediates for the stereoselective synthesis of β-lactams. Staudinger reaction between these compounds and phenoxyketenes, generated in situ, from the corresponding acid chlorides in the presence of triethylamine, provides a mixture of diastereomeric cis-β-lactams. Attempts have been made to separate them using column chromatography and their ratios determined through 1H NMR data.
- Kanwar, Seema,Saluja, Aarti,Khurana,Sharma
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p. 137 - 141
(2007/10/03)
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- The 'SuperQuat' (R)-4-phenyl-5,5-dimethyl oxazolidin-2-one as an effective chiral auxiliary for conjugate additions: Asymmetric synthesis of (-)-aplysillamide B.
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(R)-4-Phenyl-5,5-dimethyl-oxazolidin-2-one, readily available from D- phenylglycine, is shown to be an effective chiral auxiliary for stereoselective conjugate additions to attached α,β-unsaturated N-acyl moieties. Its utility is demonstrated by the asymmetric synthesis of the antifungal, antibacterial (-)-Aplysillamide B.
- Davies, Stephen G.,Sanganee, Hitesh J.,Szolcsanyi, Peter
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p. 3337 - 3354
(2007/10/03)
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- Chiral auxiliaries
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This invention relates to novel compounds of general formula (I): STR1 wherein the two R1 groups are identical lower alkyl groups or together form a lower alkylene group; R2 and R3 are both different and are selected from hydrogen atoms or organic groups; X and X', which may be the same or different, are selected from O, S and NR, where R represents an organic group; and the asterisk denotes that the configurations of R2 and R3 are such that the compound (I) is in substantially enantiomerically pure 4R- or 4S-form. The compounds are useful chiral auxiliaries to which a wide range of, for example, acyl groups containing prochiral centers may be readily and reversibly coupled to the 3-position amino group.
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- 9. Les β-cetonitriles groupes protecteurs de la fonction amine. Preparation d'amino-alcools
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β-Ketonitrile-Derived Protecting Groups of the Amino Function.Synthesis of Amino Alcohols.The amino group of natural L-amino acid esters is protected by condensation with 2-oxocyclopentanenitrile (1) or 2-formyl-2-phenylacetonitrile (10).Only the ester group of the formed cyanoenamino esters 2 and 11 reacts with nucleophilic reagents such as organometallics (RMgX, RLi), borohydrides, or metal amides, whereas the cyanoenamino group is unchanged (Schemes 1 and 2).Cyanoenamino alcohols obtained by reduction of cyanoenamino esters 2 are hydrolyzed under acidic conditions to amino alcohols with retention of the configuration of the starting amino acid.This sequence of reactions allows to prepare derivatives of L-tyrosinol from (-)-L-tyrosine (see, e.g., Scheme 4).Cyanoenamino esters 11 are readily methylated at the N-atom to give N-methylated cyanoenamino esters (Scheme 3).This property is exploited on the way of multistep procedure to obtain N-methylated amino alcohols homologous to natural (-)-(1R,2S)-ephedrine.
- Abarbri, Mohamed,Guignard, Alain,Lamant, Maurice
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p. 109 - 121
(2007/10/02)
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- Alanine-derived Hosts Comprising a Roof-shaped Carbonimide Framework. Synthesis, Inclusion Formation and X-Ray Crystal Structures of Racemic and Optically Resolved Free Hosts, and their Crystalline Complexes with 3-Methylcyclohexanone
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A chiral crystalline host molecule derived from the amino acid alanine comprising a characteristic 9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide framework as an inclusion-promoting group has been synthesized in optically resolved and racemic forms and studied with regard to their inclusion behaviour.Dependent on the optical resolution state, this host forms crystalline inclusion compounds with a great variety of uncharged organic molecules ranging from protic dipolar to rather apolar compounds (78 different inclusion species) with the racemic host being more efficient.X-Ray crystal structures of the optically resolved and racemic uncomplexed host species and of their 1:1 inclusion complexes with 3-methylcyclohexanone are reported.The host hydroxy groups are always involved in O-H...O=C intramolecular hydrogen bonds.The crystal packings of both complexes are analogous, showing similar cell dimensions and space groups P21 and P21/a.Moreover, the two independent molecules in the resolved complex are almost related by a pseudo centre of symmetry.
- Weber, Edwin,Reutel, Christiane,Foces-Foces, Concepcion,Llamas-Saiz, Antonio L.
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p. 1455 - 1462
(2007/10/02)
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- KINETICS OF THE ALKALINE HYDROLYSIS OF SEVERAL N-BENZYLOXYCARBONYLDIPEPTIDE METHYL AND ETHYL ESTERS
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The reaction rates of the alkaline hydrolysis of synthesized N-protected dipeptide methyl and ethyl esters were studied systematically.From the kinetic data the energies of activation, the pre-exponential factors and the reference values at 40 deg C were calculated.The rate of hydrolysis shows to be strongly dependent on the C-terminal amino acid in the sequence Gly >> Ala/Met/Phe > Leu >> Val/Pro.Surprisingly the N-terminal amino acid also exerts an effect, but in a different sequence.N-Terminal Phe in particular shows a relative accelerating effect.Remarkable is the significantly faster ester hydrolysis of glycine containing dipeptide ethyl esters in ethanol/water compared to the corresponding methyl esters in methanol/water.
- Hoogwater, D. A.,Peereboom, M.
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p. 5325 - 5332
(2007/10/02)
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- PREPARATION AND 31P NMR STUDIES OF PLATINUM COMPLEXES OF SOME CHIRAL, BIDENTATE PHOSPHINES
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Two chiral diphosphines of formula RN(P(C6H5)2)2, S-peap and S-alap, have been prepared from S-α-phenethylamine and the ethyl ester of S-alanine, respectively.Their syntheses, and the preparation of the achiral diphosphine beap, N,N'-bis(diphenylphosphino)-N,N'-dibenzylethylenediamine, are described.Platinum complexes of these bidentate ligands of formula Pt(chelate)CH3Cl and ClO4 (X=acetone; p-YC5H4N, when Y=CH3, C2H5, CHO, CO2CH3, H and N(CH3)2; and a series of monodentate, Group V donor ligands, P(C2H5)3, P(C3H7)3, P(C8H17)3, PCH3(C6H5)2, P(CH3)2C6H5, P(C6H5)3, P(C6H11)(C6H5)2, P(C6H11)2C6H5, P(C6H11)3, P(C6H5)2N(C2H5)2, As(C6H5)3 and Sb(C6H5)3) have been prepared and their 1H and 31P NMR parameters recorded.The cationic pyridine complexes show a correlation of the ρ values of the para substituent to some of the 31P chemical shifts and coupling constants.The steric and electronic properties of the diphosphine ligands have been investigated by comparing their 31P NMR parameters with those of analogous complexes containing (+)-diop and S,S-chiraphos.
- Payne, Nicholas C.,Stephan, Douglas W.
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p. 203 - 222
(2007/10/02)
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- Aqueous Solutions Containing Amino Acids and Peptides. Part 11.-Enthalpy of Dilution of Single and Binary Solute Solutions of N-Acetylglycine Amide, N-Acetyl-L-alanine Amide, N-Acetyl-L-valine Amide and N-Acetyl-L-leucine Amide at 298.15 K
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The enthalpies of dilution of aqueous solutions containing N-acetylglycine amide (G), N-acetyl-L-alanine amide (A), N-acetyl-L-valine amide (V) and N-acetyl-L-leucine amide (L) and equimolal solutions of G+A, G+V, G+L, A+V, A+L and V+L have been measured at 298.15 K.The results obtained have been used to calculate the pairwise enthalpy coefficients for like-like and like-unlike solute interactions.These coefficients have been compared with the predictions of the group additivity approach proposed earlier by Savage and Wood.The group additivity approach works well considering the experimental error and the standard deviation of the original correlations although it seems likely that some refinement of the group interaction parameters is required.
- Blackburn, G. Michael,Lilley, Terence H.,Walmsley, Elizabeth
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p. 915 - 922
(2007/10/02)
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