- Study of 1,3-dipolar cycloaddition of amino-acid azomethines and Juglone
-
Novel 2,3,4,9-tetrahydro- and 4,9-dihydro-1H-benzo[f]isoindole derivatives were synthesized from Juglone and amino-acid azomethines in 74–85% yields via 1,3-dipolar cycloaddition. The stereo- and regioselectivity of cycloaddition was confirmed by NMR spec
- Syngaevsky, Vadym,Karkhut, Andrew,Polovkovych, Sviatoslav,Gzella, Andrzej,Lesyk, Roman,Novikov, Volodymyr
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p. 3165 - 3173
(2020/07/27)
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- Re-Engineering Organocatalysts for Asymmetric Friedel-Crafts Alkylation of Indoles through Computational Studies
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The discovery of efficient organocatalysts is generally carried out by thorough experimental screening of different candidates. We recently reported an efficient organocatalyst for iminium-ion-based asymmetric Diels-Alder reactions following a rational design approach. This result encouraged us to test this optimal catalyst in the mechanistically related Friedel-Crafts alkylation of indoles, but to our surprise, almost null enantioselectivity was observed. The results did not significantly improve with structurally related catalysts, and a totally unexpected facial selectivity inversion was also noticed. Using DFT calculations by modeling the competing transition structures with ONIOM, we could unravel the origins of those findings, further employed to predict the most efficient catalyst for this new transformation. The computational results were validated experimentally (up to 92:8 er), providing another successful example of a general strategy to accelerate catalyst development which still remains underexplored.
- Gerosa, Gabriela G.,Marcarino, Maribel O.,Spanevello, Rolando A.,Suárez, Alejandra G.,Sarotti, Ariel M.
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p. 9969 - 9978
(2020/09/03)
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- Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma
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Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clinical development that was specifically designed for efficient and rapid protein degradation kinetics.
- Hansen, Joshua D.,Correa, Matthew,Nagy, Mark A.,Alexander, Matt,Plantevin, Veronique,Grant, Virginia,Whitefield, Brandon,Huang, Dehua,Kercher, Timothy,Harris, Roy,Narla, Rama Krishna,Leisten, Jim,Tang, Yang,Moghaddam, Mehran,Ebinger, Katalin,Piccotti, Joseph,Havens, Courtney G.,Cathers, Brian,Carmichael, James,Daniel, Thomas,Vessey, Rupert,Hamann, Lawrence G.,Leftheris, Katerina,Mendy, Derek,Baculi, Frans,Lebrun, Laurie A.,Khambatta, Gody,Lopez-Girona, Antonia
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p. 6648 - 6676
(2020/09/11)
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- Boron Dipyrromethene (BODIPY) as Electron-Withdrawing Group in Asymmetric Copper-Catalyzed [3+2] Cycloadditions for the Synthesis of Pyrrolidine-Based Biological Sensors
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In this work, we describe the use of Boron Dipyrromethene (BODIPY) as electron-withdrawing group for activation of double bonds in asymmetric copper-catalyzed [3+2] cycloaddition reactions with azomethine ylides. The reactions take place under smooth conditions and with high enantiomeric excess for a large number of different substituents, pointing out the high activation of the alkene by using a boron dipyrromethene as electron-withdrawing group. Experimental, theoretical studies and comparison with other common electron-withdrawing groups in asymmetric copper-catalyzed [3+2] cycloadditions show the reasons of the different reactivity of the boron dipyrromethene derivatives, which can be exploited as a useful activating group in asymmetric catalysis. Additional experiments show that the so obtained pyrrolidines can be employed as biocompatible biosensors, which can be located in the endosomal compartments and do not present toxicity in three cell lines. (Figure presented.).
- Alemán, José,Asenjo-Pascual, Juan,Cordani, Marco,Díaz-Tendero, Sergio,Fraile, Alberto,Martín-Somer, Ana,Milán Rois, Paula,Rigotti, Thomas,Somoza, álvaro
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supporting information
(2020/02/20)
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- Synthesis and Electrochemical Estimation of DNA-Binding Capacity of Novel Ferrocene-Containing Pyrrolidines
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The design, synthesis, spectral and electrochemical characterization of a series of novel pyrrolidine derivatives have been described. The synthesis was achieved by 1,3-dipolar cycloaddition of azomethine ylides and ferrocene-substituted chalcones, while
- Bogdanovi?, Goran A.,Bugarinovi?, Jovana,Damljanovi?, Ivan,Mini?, Aleksandra,Pe?i?, Marko,Stevanovi?, Dragana,Todosijevi?, Anka
-
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- Synthesis of novel multi-functionalized pyrrolidines by [3 + 2] dipolar cycloaddition of azomethine ylides and vinyl ketones
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Abstract: An efficient and easy synthetic route to substituted pyrrolidine derivatives has been established through [3 + 2] dipolar cycloaddition of vinyl ketones and azomethine ylides. The reactions proceed smoothly, under mild conditions, affording mode
- Pe?i?, Marko S.,Bugarinovi?, Jovana P.,Mini?, Aleksandra,Ili? Komatina, Danijela,Pejovi?, Anka,?mit, Biljana,Stevanovi?, Dragana,Damljanovi?, Ivan
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p. 663 - 679
(2019/03/11)
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- Utilization of fluoroform for difluoromethylation in continuous flow: A concise synthesis of α-difluoromethyl-amino acids
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Fluoroform (CHF3) can be considered as an ideal reagent for difluoromethylation reactions. However, due to the low reactivity of fluoroform, only very few applications have been reported so far. Herein we report a continuous flow difluoromethyl
- K?ckinger, Manuel,Ciaglia, Tanja,Bersier, Michael,Hanselmann, Paul,Gutmann, Bernhard,Kappe, C. Oliver
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supporting information
p. 108 - 112
(2018/01/12)
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- Synthesis and Deployment of an Elusive Fluorovinyl Cation Equivalent: Access to Quaternary α-(1′-Fluoro)vinyl Amino Acids as Potential PLP Enzyme Inactivators
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Developing specific chemical functionalities to deploy in biological environments for targeted enzyme inactivation lies at the heart of mechanism-based inhibitor development but also is central to other protein-tagging methods in modern chemical biology including activity-based protein profiling and proteolysis-targeting chimeras. We describe here a previously unknown class of potential PLP enzyme inactivators; namely, a family of quaternary, α-(1′-fluoro)vinyl amino acids, bearing the side chains of the cognate amino acids. These are obtained by the capture of suitably protected amino acid enolates with β,β-difluorovinyl phenyl sulfone, a new (1′-fluoro)vinyl cation equivalent, and an electrophile that previously eluded synthesis, capture and characterization. A significant variety of biologically relevant AA side chains are tolerated including those for alanine, valine, leucine, methionine, lysine, phenylalanine, tyrosine, and tryptophan. Following addition/elimination, the resulting transoid α-(1′-fluoro)-β-(phenylsulfonyl)vinyl AA-esters undergo smooth sulfone-stannane interchange to stereoselectively give the corresponding transoid α-(1′-fluoro)-β-(tributylstannyl)vinyl AA-esters. Protodestannylation and global deprotection then yield these sterically encumbered and densely functionalized quaternary amino acids. The α-(1′-fluoro)vinyl trigger, a potential allene-generating functionality originally proposed by Abeles, is now available in a quaternary AA context for the first time. In an initial test of this new inhibitor class, α-(1′-fluoro)vinyllysine is seen to act as a time-dependent, irreversible inactivator of lysine decarboxylase from Hafnia alvei. The enantiomers of the inhibitor could be resolved, and each is seen to give time-dependent inactivation with this enzyme. Kitz-Wilson analysis reveals similar inactivation parameters for the two antipodes, L-α-(1′-fluoro)vinyllysine (Ki = 630 ± 20 μM; t1/2 = 2.8 min) and D-α-(1′-fluoro)vinyllysine (Ki = 470 ± 30 μM; t1/2 = 3.6 min). The stage is now set for exploration of the efficacy of this trigger in other PLP-enzyme active sites.
- McCune, Christopher D.,Beio, Matthew L.,Sturdivant, Jill M.,De La Salud-Bea, Roberto,Darnell, Brendan M.,Berkowitz, David B.
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supporting information
p. 14077 - 14089
(2017/10/17)
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- Stereoselective and Site-Specific Allylic Alkylation of Amino Acids and Small Peptides via a Pd/Cu Dual Catalysis
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We report a stereoselective and site-specific allylic alkylation of Schiff base activated amino acids and small peptides via a Pd/Cu dual catalysis. A range of noncoded α,α-dialkyl α-amino acids were easily synthesized in high yields and with excellent enantioselectivities (up to >99% ee). Furthermore, a direct and highly stereoselective synthesis of small peptides with enantiopure α-alkyl or α,α-dialkyl α-amino acids residues incorporated at specific sites was accomplished using this dual catalyst system.
- Huo, Xiaohong,He, Rui,Fu, Jingke,Zhang, Jiacheng,Yang, Guoqiang,Zhang, Wanbin
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supporting information
p. 9819 - 9822
(2017/08/02)
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- Ag2CO3/CA-AA-amidphos multifunctional catalysis in the enantioselective 1,3-dipolar cycloaddition of azomethine ylides
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The new Ag2CO3/CA-AA-amidphos complexes have been demonstrated as highly efficient multifunctional catalysts in the asymmetric 1,3-dipolar cycloaddition of azomethine ylides. Under optimal conditions, highly functionalized endo-4 pyrrolidines were obtained with excellent yields (up to 99% yield) and enantioselectivities (up to 96% ee).
- Wang, Haifei,Deng, Qifu,Zhou, Zhipeng,Hu, Shunqin,Liu, Zhiguo,Zhou, Li-Yi
-
supporting information
p. 404 - 407
(2016/02/18)
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- Diastereoselective synthesis of novel aza-diketopiperazines via a domino cyclohydrocarbonylation/addition process
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Herein, we report an unprecedented, short and diastereo-selective synthesis of newly reported aza-diketopiperazine (aza-DKP) scaffolds starting from amino acids. The strategy is based on a Rh(i)-catalyzed hydroformylative cyclohydrocarbonylation of allyl-substituted aza-DKP, followed by a diastereoselective functionalization of the platform. This methodology allows the synthesis of novel bicyclic and tricyclic aza-DKP scaffolds incorporating six- or seven-membered rings, with potential applications in medicinal chemistry. This journal is the Partner Organisations 2014.
- Regenass, Pierre,Margathe, Jean-Fran?ois,Mann, André,Suffert, Jean,Hibert, Marcel,Girard, Nicolas,Bonnet, Dominique
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supporting information
p. 9657 - 9660
(2014/08/18)
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- Stereospecific synthesis of pyrrolidines with varied configurations via 1,3-dipolar cycloadditions to sugar-derived enones
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Enantiomerically pure pyrrolidines have been obtained by 1,3-dipolar cycloaddition of stabilized azomethine ylides and sugar enones (dihydropyranones) derived from pentoses. Thus, the S-enone (menthyl 3,4-dideoxy-(1S)-pent-3-enopyranosid-2-ulose) was prepared from d-xylose, while the R analogue was obtained from l-arabinose. The dipoles were generated in situ from α-arylimino esters of common amino acids (glycine, alanine, or phenylalanine) and aromatic aldehydes (benzaldehyde, 3-formylpyridine and 4-methoxybenzaldehyde). Under optimized conditions, the cycloaddition reactions were highly diastereo- and regioselective to yield, in most of the cases, a very major adduct of the 16 theoretically possible. The diastereoselectivity relies on the strict stereocontrol exerted by the stereogenic center of the pyranone. Thus, the (S)-enone, derived from d-xylose, gave tetrasubstituted pyrrolidines having a defined stereochemistry for the four stereocenters of the ring, while they had the opposite configuration when starting from the (R)-dihydropyranone. Furthermore, some endo-cycloadducts underwent isomerization of the carbons vicinal to the nitrogen atom to afford pyrrolidines with a rather unusual stereochemistry for the direct dipolar cycloadditions.
- Udry, Guillermo A. Oliveira,Repetto, Evangelina,Varela, Oscar
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p. 4992 - 5006
(2014/06/23)
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- Design, synthesis, and functional evaluation of leukocyte function associated antigen-1 antagonists in early and late stages of cancer development
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The integrin leukocyte function associated antigen 1 (LFA-1) binds the intercellular adhesion molecule 1 (ICAM-1) by its αL-chain inserted domain (I-domain). This interaction plays a key role in cancer and other diseases. We report the structure-based design, small-scale synthesis, and biological activity evaluation of a novel family of LFA-1 antagonists. The design led to the synthesis of a family of highly substituted homochiral pyrrolidines with antiproliferative and antimetastatic activity in a murine model of colon carcinoma, as well as potent antiadhesive properties in several cancer cell lines in the low micromolar range. NMR analysis of their binding to the isolated I-domain shows that they bind to the I-domain allosteric site (IDAS), the binding site of other allosteric LFA-1 inhibitors. These results provide evidence of the potential therapeutic value of a new set of LFA-1 inhibitors, whose further development is facilitated by a synthetic strategy that is versatile and fully stereocontrolled.
- San Sebastián, Eider,Zimmerman, Tahl,Zubia, Aizpea,Vara, Yosu,Martin, Elyette,Sirockin, Finton,Dejaegere, Annick,Stote, Roland H.,Lopez, Xabier,Pantoja-Uceda, David,Valcárcel, María,Mendoza, Lorea,Vidal-Vanaclocha, Fernando,Cossío, Fernando P.,Blanco, Francisco J.
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p. 735 - 747
(2013/03/28)
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- An efficient synthesis of (±) solenopsin A
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The efficient total synthesis of ( ± ) solenopsin A ( 9 ) was achieved in a series of eight steps starting from readily available N -Bn-N -Boc alanine derivative 1. Copyright by Walter de Gruyter.
- Arevalo-Garcia, Enzo B.
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experimental part
p. 61 - 65
(2012/08/08)
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- Synthesis of aromatic α-aminoesters: Palladium-catalyzed long-range arylation of primary Csp3-H bonds
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Remote control: The title reaction for β-Iζ arylation of α-amino esters with aryl bromides is described. This reaction, which occurs selectively at the terminal position of linear alkyl chains, gives rise to synthetically useful (hetero)arylalanines and homologues after debenzylation (see scheme). Copyright
- Aspin, Sam,Goutierre, Anne-Sophie,Larini, Paolo,Jazzar, Rodolphe,Baudoin, Olivier
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supporting information
p. 10808 - 10811
(2013/01/15)
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- Chemoselective reactions of trimethylsilylpropynal with aminopyrimidines and amino acid esters
-
Highly efficient chemoselective 1,2-addition of 2-aminopyrimidines and D,L-amino acid esters to substituted propynals was performed. Acid-catalyzed addition of 2-aminopyrimidine and 2-amino-4-methylpyrimidine to trimethylsilyl- and phenylpropynals gave pr
- Mareev,Mareeva,Andreev,Gulyaev,Mitroshina,Medvedeva
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experimental part
p. 1544 - 1550
(2012/03/08)
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- Asymmetric construction of 3-vinylidene-pyrrolidine derivatives containing allene moiety via Ag(i)/TF-BiphamPhos-catalyzed 1,3-dipolar cycloaddition of azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene) malonate
-
Catalytic asymmetric 1,3-dipolar cycloaddition of various azomethine ylides with diethyl 2-(3,3-diphenylpropa-1,2-dienylidene)malonate has been developed successfully with good to excellent enantioselectivity for the effcient construction of 3-vinylidene-pyrrolidine derivatives containing a unique allene moiety.
- Xue, Zhi-Yong,Fang, Xin,Wang, Chun-Jiang
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supporting information; experimental part
p. 3622 - 3624
(2011/06/17)
-
- Design of small-molecule thrombin inhibitors based on the cis-5-phenylproline scaffold
-
The design of novel organic compounds containing no strongly basic amidine or guanidine functional groups typical of serine protease inhibitors was performed to develop an oral anticoagulant drug. A three-dimensional computational model for thrombin active site was constructed and optimized for docking of small-molecule organic compounds and calculating the energies of inhibitor-enzyme interactions. Novel racemic derivatives of 1-[2-(4- chlorophenylthio)acetyl]-5-phenylpyrrolidine-2,4-dicarboxylic acids were synthesized for which Cl-π interactions between the inhibitors and the S1 pocket of thrombin active site are predicted by modeling. The compounds synthesized deactivate thrombin in vitro and the inhibition properties show good correlations with the results of calculations.
- Kudryavtsev,Shulga,Chupakhin,Churakov,Datsuk,Zabolotnev,Zefirov
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scheme or table
p. 685 - 693
(2012/02/05)
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- Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination
-
Cyclisations of homoallylic sulfonamides proceed smoothly via carbenium ion generation using trifluoromethanesulfonic (triflic) acid, the ease of cyclisation being directly related to the ion stability to give good to excellent yields of the corresponding pyrrolidines. Both toluene- and nitrophenyl-sulfonyl groups are suitable for all substrates tested whereas the corresponding carbamates are only useful in cases of tertiary and highly stabilised carbenium ions. Polyene-derived sulfonamides can also be cyclised to the corresponding polycyclic systems in remarkably high yields, in reactions reminiscent of related cascades encountered in terpene biosynthesis.
- Griffiths-Jones (née Haskins), Charlotte M.,Knight, David W.
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experimental part
p. 4150 - 4166
(2010/07/05)
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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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- Highly enantioselective 1,3-dipolar cycloaddition of azomethine ylides catalyzed by AgOAc/TF-BiphamPhos
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A novel and highly efficient AgOAc/TF-BiphamPhos catalytic system shows excellent reactivity, diastereo-/enantioselectivity and structural scope in asymmetric 1,3-dipolar cycloaddition of azomethine ylides, especially derived from various α-substituted α-amino acids, with N-substituted maleimides and other electron-deficient alkenes.
- Wang, Chun-Jiang,Xue, Zhi-Yong,Liang, Gang,Lu, Zhou
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supporting information; experimental part
p. 2905 - 2907
(2009/12/01)
-
- Silver acetate/TF-biphamphos-catalyzed endo-selective enantioselective 1,3-dipolar cycloaddition of azomethine ylides with vinyl phenyl sulfone
-
The first catalytic endo-selective 1,3-dipolar cycloaddition of azomethine ylides and vinyl phenyl sulfone has been developed successfully. The highly efficient silver acetate (AgOAc)/TF-BiphamPhos catalytic system exhibited high reactivity, excellent diastereoselectivity (>98:2), good enantioselectivity (67-92% ee) and broad substrate scope under mild conditions.
- Liang, Gang,Tong, Min-Chao,Wang, Chun-Jiang
-
supporting information; experimental part
p. 3101 - 3106
(2010/04/06)
-
- Anti-MRSA agent discovery using diversity-oriented synthesis
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Beating the superbugs: Diversity-oriented synthesis using a solid-supported phosphonate unit to synthesize 242 drug-like compounds based on 18 natural-productlike scaffolds led to the discovery of gemmacin (see scheme). This new structural class of antibiotic is active towards methicillin-resistant Staphylococcus aureus (MRSA). (Chemical Equation Presented).
- Thomas, Gemma L.,Spandl, Richard J.,Glansdorp, Freija G.,Welch, Martin,Bender, Andreas,Cockfield, Joshua,Lindsay, Jodi A.,Bryant, Clare,Brown, Derek F. J.,Loiseleur, Olivier,Rudyk, Helene,Ladlow, Mark,Spring, David R.
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supporting information; experimental part
p. 2808 - 2812
(2009/02/06)
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- Solventless lactam synthesis by intramolecular cyclizations of α-iminoester derivatives under microwave irradiation
-
We have previously reported a new synthesis of amides from esters and amines under microwave irradiation, offering much higher yields than those achieved with conventional heating [1]. We have now extended these studies to the ring closure of neat iminoes
- Zradni, Fatima-Zohra,Hamelin, Jack,Derdour, Aicha
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p. 439 - 454
(2007/10/03)
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- METHODS AND COMPOSITIONS USING 4-AMINO-2-(3-METHYL-2,6-DIOXOPIPERIDIN-3-YL)-ISOINDOLE-1-3-DIONE
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This invention relates to racemic and stereomerically pure 4-amino-2-(3-methyl- 2,6-dioxopiperidin-3-yl)-isoindole-1,3-dione, and prodrugs, salts and solvates thereof. Synthesis, methods of use, and pharmaceutical compositions of racemic and stereomerical
- -
-
Page/Page column 42
(2008/06/13)
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- Stereoselective Addition of Dimethyl Thiophosphite to Imines
-
Dimethyl thiophosphite (DMTP) was synthesized from dimethyl phosphite, and the diastereoselective addition of DMTP to benzaldimines bearing chiral auxiliary groups was examined. Yields of the product α -aminophosphonothionates ranged from 17% to 75% after chromatography. The addition of DMTP to the benzaldimine derived from (S)-phenylglycinol afforded the highest diastereoselectivity (83:17), whereas addition of DMTP to the benzaldimine derived from threonine methyl ester and alanine methyl ester were far less diastereoselective, affording 38:62 and 61:39 ratios, respectively. Addition of DMTP to the benzaldimine derived from (R)-α-methylbenzylamine (78:22) and (S)-serine methyl ester (73:27) were intermediate in selectivity. DMTP addition to the imines formed between serine methyl ester and acetaldehyde and isobutyraldehyde gave 55:45 and 70:30 ratios, respectively, with the diastereoselectivity corresponding roughly to the size of the α-alkyl group. The stereochemistry of the newly formed α-stereocenters resulting from the addition of DMTP to (S)- and (R)-phenylglycinol benzaldimines was confirmed by conversion of the product α-aminophosphonothionates to the known enantiomers of phosphonophenylglycine.
- Tongcharoensirikul, Pakamas,Suarez, Alirica I.,Voelker, Troy,Thompson, Charles M.
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p. 2322 - 2326
(2007/10/03)
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- SAR study of the indole moiety of CI-988, a potent and selective CCK-B antagonist
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Due to the interesting pharmacological activity observed for CI-988, a potent and selective CCK-B receptor antagonist, we have continued to study the SAR of this antagonist. This particular study examines the importance of the indole moiety for binding affinity. The synthesis and receptor binding affinity for analogs containing functionalized indole derivatives and replacing the indole with various heterocycles are reported.
- Augelli-Szafran, Corinne E.,Purchase, Terri S.,Roth, Bruce D.,Tait, Bradley,Trivedi, Bharat K.,Wilson, Michael,Suman-Chauhan, Nirmala,Webdale, Louise
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p. 2009 - 2014
(2007/10/03)
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- New approach for the general synthesis of oxotetrahydroindoles via intramolecular cycloadditions of azomethine ylides with tethered alkynes
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A new method for the synthesis of oxotetrahydroindoles has been achieved employing an intramolecular dipolar cycloaddition approach involving mesoionic species (munchnones) with electron-deficient alkynes. The methodology is quite general and convergent as shown by the synthesis of a variety of tri- and tetrasubstituted oxotetrahydroindoles 18, 21, 24, 27, 30, and 34. LiI-based ester cleavage in the presence of an electrophilic acetylenic ketone was critical for formation of the requisite cycloaddition substrates. The cycloaddition is virtually unaffected by the presence of gem-dimethyl groups in the side chain (cf. 38). The presence of a substituted benzyl or a phenethyl moiety on nitrogen, a polarized acetylene, and an appropriate tether between dipole and dipolarophile are essential for obtaining optimal efficiency.
- Nayyar, Naresh K.,Hutchison, Darrell R.,Martinelli, Michael J.
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p. 982 - 991
(2007/10/03)
-
- Synthesis and receptor-binding affinity of dipeptoid cholecystokinin ligands
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This paper describes the synthesis of novel derivatives 4a-i, which are structurally related to PD134308 and in which the indole moiety is replaced by other aromatic groups. Cholecystokinin-A and -B (CCK-A and CCK-B) receptor binding affinities of these analogues are described and the contribution of the various rings is discussed. Several of the compounds prepared have CCK-B receptor binding values similar to that reported for PD134308 and are highly selective over the CCK-A receptor. They represent potential therapeutic agents for anxiety.
- Araldi,Donati,Oliosi,Pasquarello,Polinelli,Tarzia,Ursini,Van Amsterdam
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p. 215 - 220
(2007/10/03)
-
- Trimethylorthoformate: A Mild and Effective Dehydrating Reagent for Solution and Solid Phase Imine Formation.
-
Trimethylorthoformate has been found to be an effective dehydrating solvent for the formation of imines, both in the solid phase as well as solution phase.
- Look, Gary C.,Murphy, Martin M.,Campbell, David A.,Gallop, Mark A.
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p. 2937 - 2940
(2007/10/02)
-
- Cholecystokinin Peptidomimetics as Selective CCK-B Antagonists: Design, Synthesis, and in Vitro and in Vivo Biochemical Properties
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Antagonists of cholecystokinin-B (CCK-B) receptors have been shown to alleviate CCK4-induced panic attacks in humans and to potentiate opioid effects in animals.The clinical use of these compounds is critically dependent on their ability to cross the blood-brain barrier.In order to improve this property, new, peptoid-derived CCK-B antagonists, endowed with high affinity, selectivity, and increased lipophilicity have been developed.The affinity and selectivity of these compounds have been cheracterized in vitro and in vivo using guinea pig, rat, and mouse.Most of these compounds proved to be selective for the CCK-B receptor, the most potent analog, N--D-α-methyltryptophanyl>-N-i value of 6.1 nM for guinea pig cortex membranes in vitro and a good selectivity ratio (Ki CCK-A/Ki CCK-B = 174).Furthermore, the in vivo affinity of 26A for mouse brain CCK-B receptors, following intracerebroventricular injection at different concentrations, was found to be 10 nmol.Using competition experiments with the specific CCK-B ligand pBC 264, compound 26A was shown to cross the blood-brain barrier (0.2percent) after intraperitoneal administration in mice.This compound is therefore an interesting pharmacological tool to further elucidate the physicopathological role of endogenous CCK.
- Blommaert, Armand G.S.,Weng Jian-Hui,Dorville, Agnes,McCort, Isabelle,Ducos, Bertrand,et al.
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p. 2868 - 2877
(2007/10/02)
-
- Lithium Bromide/Triethylamine Induced Cycloaddition of N-Alkylidene 2-Amino Esters and Amides to Electron-Deficient Olefins with High Regio- and Stereoselectivity
-
The imines of 2-amino esters and amides derived from glycine, alanine, and valine are deprotonated by the action of a lithium halide and triethylamine (or DBU).The resulting anionic intermediates undergo highly regio- and stereoselective cycloadditions with a variety of olefins activated by carbonyl-type substituents to produce stereochemically defined derivatives of proline esters or amides.The scope and limitations of this novel cycloaddition are discussed.
- Tsuge, Otohiko,Kanemasa, Shuji,Yoshioka, Manabu
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p. 1384 - 1391
(2007/10/02)
-
- X=Y-ZH Systems as Potential 1,3-Dipoles. Part 1. Background and Scope
-
X=Y-ZH Systems are considered in general terms and divided into four classes according to the number of constituent atoms that possess lone-pair electrons.Those systems in which the central Y atom possesses a lone pair are shown to be capable of participa
- Grigg, Ronald,Gunaratne, H. Q. Nimal,Kemp, James
-
-