- Use of (S)-N-tert-butoxycarbonylaziridine-2-carboxylate derivatives for α-amino acid synthesis
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(S)-tert-Butyl-N-tert-butoxycarbonylaziridine-2-carboxylate and (S)-tert-butyl-N-tert-butoxycarbonylaziridine-2-carboxamide were synthesised and found to react with copper 'catalysed' Grignard reagents to give protected α-amino acids in moderate to good yields.
- Baldwin, Jack E.,Farthing, Christopher N.,Russell, Andrew T.,Schofield, Christopher J.,Spivey, Alan C.
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- 2-[ 18 F]Fluorophenylalanine: Synthesis by Nucleophilic 18 F-Fluorination and Preliminary Biological Evaluation
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2-[ 18 F]Fluorophenylalanine (2-[ 18 F]FPhe), a promising PET tracer for imaging of cerebral infarction and tumors, was efficiently prepared from an easily accessible iodonium salt precursor using Cu-mediated radiofluorination under 'low base' or 'minimalist' conditions. Whereas significant racemization was initially observed if the 'minimalist' protocol was applied for radiolabeling, it was completely suppressed by the careful adjustment of 18 F - preprocessing. The initial biological study revealed a higher uptake of 2-[ 18 F]FPhe in different tumor cells in comparison to that of [ 18 F]FET. In contrast to 4-[ 18 F]FPhe, which suffered from rapid defluorination in vivo, 2-[ 18 F]FPhe demonstrated a sufficient in vivo stability. Conclusively, 2-[ 18 F]FPhe is a promising PET probe that is now readily available using Cu-mediated radiofluorination under 'minimalist' or 'low base' conditions. The simplicity of the translation of the proposed procedures to automated synthesis modules allows a broad biological evaluation of 2-[ 18 F]FPhe. Notably, a novel protocol for the preparation of N -Boc protected amino acids from the respective Ni-Schiff base complexes was developed that avoided application of strongly acidic conditions.
- Modemann, Daniel J.,Zlatopolskiy, Boris D.,Urusova, Elizaveta A.,Zischler, Johannes,Craig, Austin,Ermert, Johannes,Guliyev, Mehrab,Endepols, Heike,Neumaier, Bernd
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p. 664 - 676
(2019/01/23)
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- Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1)
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The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.
- Chien, Huan-Chieh,Colas, Claire,Finke, Karissa,Springer, Seth,Stoner, Laura,Zur, Arik A.,Venteicher, Brooklynn,Campbell, Jerome,Hall, Colton,Flint, Andrew,Augustyn, Evan,Hernandez, Christopher,Heeren, Nathan,Hansen, Logan,Anthony, Abby,Bauer, Justine,Fotiadis, Dimitrios,Schlessinger, Avner,Giacomini, Kathleen M.,Thomas, Allen A.
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p. 7358 - 7373
(2018/08/06)
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- Synthesis of l-[4-11C]Asparagine by Ring-Opening Nucleophilic 11C-Cyanation Reaction of a Chiral Cyclic Sulfamidate Precursor
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The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains
- Xu, Youwen,Cankaya, Aylin Sibel,Hoque, Ruma,Lee, So Jeong,Shea, Colleen,Kersting, Lena,Schueller, Michael,Fowler, Joanna S.,Szalda, David,Alexoff, David,Riehl, Barbara,Gleede, Tassilo,Ferrieri, Richard A.,Qu, Wenchao
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p. 6848 - 6853
(2018/04/25)
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- TRANSESTERIFICATION REACTION BY MEANS OF IRON CATALYST
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Provided is a catalyst for transesterification reactions, which contains an iron salen complex. Also provided is a method for producing an ester compound, which is characterized by carrying out a transesterification reaction between a starting material ester and a starting material alcohol with use of the catalyst.
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Paragraph 0142; 0143
(2017/10/10)
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- μ-Oxo-Dinuclear-Iron(III)-Catalyzed O-Selective Acylation of Aliphatic and Aromatic Amino Alcohols and Transesterification of Tertiary Alcohols
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A highly chemoselective and reactive μ-oxo-dinuclear iron(III) salen catalyst for transesterification was developed. The developed iron complex catalyzed acylation of aliphatic amino alcohols with nearly perfect O-selectivity, even when using activated esters, for which chemoselectivity is more difficult to control. In addition, O-selective transesterification of aromatic amino alcohols was achieved for the first time. The high activity of the iron complex enabled the use of sterically congested tertiary alcohols, including unprecedented tert-butanol.
- Horikawa, Rikiya,Fujimoto, Chika,Yazaki, Ryo,Ohshima, Takashi
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supporting information
p. 12278 - 12281
(2016/08/24)
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- Decarboxylative Cross-Electrophile Coupling of N-Hydroxyphthalimide Esters with Aryl Iodides
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A new method for the decarboxylative coupling of alkyl N-hydroxyphthalimide esters (NHP esters) with aryl iodides is presented. In contrast to previous studies that form alkyl radicals from carboxylic acid derivatives, no photocatalyst, light, or arylmetal reagent is needed, only nickel and a reducing agent (Zn). Methyl, primary, and secondary alkyl groups can all be coupled in good yield (77% ave yield). One coupling with an acid chloride is also presented. Stoichiometric reactions of (dtbbpy)Ni(2-tolyl)I with an NHP ester show for the first time that arylnickel(II) complexes can directly react with NHP esters to form alkylated arenes.
- Huihui, Kierra M. M.,Caputo, Jill A.,Melchor, Zulema,Olivares, Astrid M.,Spiewak, Amanda M.,Johnson, Keywan A.,Dibenedetto, Tarah A.,Kim, Seoyoung,Ackerman, Laura K. G.,Weix, Daniel J.
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supporting information
p. 5016 - 5019
(2016/05/19)
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- A mild, copper-catalysed amide deprotection strategy: Use of tert-butyl as a protecting group
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Mild methods for the deprotection of organic substrates are of fundamental importance in synthetic chemistry. A new room temperature method using a catalytic amount of Cu(OTf)2is reported. This allows use of the tert-butyl group as an amide protecting group. The methodology is also extended to Boc-deprotection.
- Evans, Vikki,Mahon, Mary F.,Webster, Ruth L.
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supporting information
p. 7593 - 7597
(2014/12/10)
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- Guanidinium Ylide mediated aziridination from arylaldehydes: Scope and limitations in the formation of unactivated 3-arylaziridine-2-carboxylates
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The scope and limitations of guanidinium ylide mediated aziridinations from arylaldehydes yielding unactivated 3-arylaziridine-2-carboxylates, applicable to asymmetric synthesis, are discussed. Georg Thieme Verlag Stuttgart. New York.
- Oda, Yukiko,Hada, Kihito,Miyata, Marie,Takahata, Chisato,Hayashi, Yukiko,Takahashi, Masato,Yajima, Naoki,Fujinami, Makiko,Ishikawa, Tsutomu
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p. 2201 - 2219
(2014/08/18)
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- Versatile selective α-carboxylic acid esterification of N-protected amino acids and peptides by alcalase
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Under continuous removal of water, the industrial protease Alcalase allows selective synthesis of α-carboxylic acid methyl, ethyl, benzyl, allyl, 2-(trimethylsilyl)ethyl, and tert-butyl esters of amino acids and peptides under mild conditions in very high
- Nuijens, Timo,Cusan, Claudia,Kruijtzer, John A. W.,Rijkers, Dirk T. S.,Liskamp, Rob M. J.,Quaedflieg, Peter J. L. M.
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scheme or table
p. 809 - 814
(2009/07/11)
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- Kinetic resolution of racemic carboxylic acids by an L-histidine-derived sulfonamide-induced enantioselective esterification reaction
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(Chemical Equation Presented) The direct and catalytic kinetic resolution of racemic carboxylic acids bearing a Bronsted base such as O-protected α-hydroxy carboxylic acids and N-protected α-amino acids has been accomplished through an L-histidine-derived sulfonamide-induced enantioselective esterification reaction with tert-butyl alcohol for the first time. Highly asymmetric induction [S(kfast/kslow) = up to 56] has been achieved under the equilibrium between a chiral catalyst and two diastereomeric acylammonium salts through an intramolecular hydrogen-bonding interaction.
- Ishihara, Kazuaki,Kosugi, Yuji,Umemura, Shuhei,Sakakura, Akira
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supporting information; experimental part
p. 3191 - 3194
(2009/05/27)
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- Access to enantioenriched α-amino esters via rhodium-catalyzed 1,4-addition/enantioselective protonation
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Conjugate addition of potassium trifluoro(organo)borates 2 to dehydroalanine derivatives 1, mediated by a chiral rhodium catalyst and in situ enantioselective protonation, afforded straightforward access to a variety of protected α-amino esters 3 with high yields and enantiomeric excesses up to 95%. Among the tested chiral ligands and proton sources, Binap, in combination with guaiacol (2-methoxyphenol), an inexpensive and nontoxic phenol, afforded the highest asymmetric inductions. Organostannanes have also shown to participate in this reaction. By a fine-tuning of the ester moiety, and using Difluorophos as chiral ligand, increased levels of enantioselectivity, generally close to 95%, were achieved. Deuterium labeling experiments revealed, and DFT calculation supported, an unusual mechanism involving a hydride transfer from the amido substituent to the α carbon explaining the high levels of enantioselectivity attained in controlling this α chiral center.
- Navarre, Laure,Martinez, Remi,Genet, Jean-Pierre,Darses, Sylvain
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p. 6159 - 6169
(2008/12/20)
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- First total synthesis of Mer-N5075A and a diastereomeric mixture of α and β-MAPI, new HIV-I protease inhibitors from a species of Streptomyces
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Mer-N5075A (1) and α-MAPI and β-MAPI (2 and 3) produced from a species of Streptomyces are new anomalous tetrapeptides having potential HIV-I protease inhibitory activity. The first total synthesis of 1 and a diastereomeric mixture of 2 and 3 was achieved
- Konda, Yaeko,Takahashi, Yukihiro,Arima, Shiho,Sato, Noriko,Takeda, Kazuyoshi,Dobashi, Kazuyuki,Baba, Masanori,Harigaya, Yoshihiro
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p. 4311 - 4321
(2007/10/03)
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- Selective nitrolytic deprotection of N-BOC-amines and N-BOC-amino acids derivatives
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The extension of the deprotection procedure using HNO3 in CH2Cl2 to a number of appropriately selected N-BOC-masked amines and derivatives of natural amino acids was investigated. The method was found to work effectively with almost all tested substrates, with the exception of activated aromatic amines and heterocycles which underwent unavoidable faster oxidation. Alanine, phenylalanine, serine and lysine derivatives were efficiently deprotected, as well as dipeptide Ala-Phe, preserving the configuration of the substrates and without affecting copresent Z and ester functions, with a remarkable selectivity towards acid sensitive t-butyl esters. The obtained amino acids esters, isolated and characterized in the form of nitrates salts, proved to be suitable intermediates to be used in peptide synthesis.
- Strazzolini, Paolo,Melloni, Tiziana,Giumanini, Angelo G
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p. 9033 - 9043
(2007/10/03)
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- First total synthesis of Mer-N5075A, a new HIV-I protease inhibitor from Streptomyces chromofuscus
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The first total synthesis of Mer-N5075A (1), a new potential HIV-I protease inhibitor produced from Streptomyces chromofuscus, was achieved. The synthetic method is available for Mer-N5075A analogues such as α-MAPI (2), GE20372 A (4) and other chemically
- Konda, Yaeko,Takahashi, Yukihiro,Mita, Hiroka,Takeda, Kazuyoshi,Harigaya, Yoshihiro
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p. 345 - 346
(2007/10/03)
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