- The novel and efficient direct synthesis of N,O-acetal compounds using a hypervalent iodine(III) reagent: An improved synthetic method for a key intermediate of discorhabdins
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The use of hypervalent iodine(III) reagents allowed us to develop the novel and efficient direct synthesis of N,O-acetal compounds via the oxidative fragmentation reaction of α-amino acids or α-amino alcohols; furthermore, we succeeded in developing an im
- Harayama, Yu,Yoshida, Masako,Kamimura, Daigo,Kita, Yasuyuki
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Read Online
- Preparation method of Wittig-Horner reagent
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A preparation method of a Wittig-Horner reagent is disclosed. According to the preparation method of the Wittig-Horner reagent provided by the invention, a compound with a structure as shown in a formula (I) and a glyoxylic acid aqueous solution with a sp
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Paragraph 0030-0032; 0035-0037
(2021/07/31)
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- Total Synthesis and Structure-Activity Relationships Study of Odilorhabdins, a New Class of Peptides Showing Potent Antibacterial Activity
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The spread of antibiotic-resistant pathogens is a growing concern, and new families of antibacterials are desperately needed. Odilorhabdins are a new class of antibacterial compounds that bind to the bacterial ribosome and kill bacteria through inhibition
- Sarciaux, Matthieu,Pantel, Lucile,Midrier, Camille,Serri, Marine,Gerber, Cristelle,Marcia De Figueiredo, Renata,Campagne, Jean-Marc,Villain-Guillot, Philippe,Gualtieri, Maxime,Racine, Emilie
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p. 7814 - 7826
(2018/09/06)
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- Reversible Folding of a β-Hairpin Peptide by a Metal-Chelating Amino Acid
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5-(1-Hydroxy-pyridin-2(1H)-onyl)-l-alanine (Hop) is a N-hydroxy-1,2-pyridone functionalized α-amino acid with the desired metal-chelating properties of DOPA (3,4-dihydroxy phenylalanine) but without its unwanted redox activity. The Fmoc-protected amino acid Fmoc-l-Hop(tBu)-OH (11) was synthesized from glycine phosphonate followed by enzymatic hydrolysis of the methyl ester yielding the Hop l-isomer in 96 % ee. The amino acid 11 is used in automated peptide synthesis for the assembly of a 14mer β-hairpin peptide with the sequence [dsb1, 14]H-CHXETGKHGHKLVC-OH (X=W, l-Hop). While the 10 π electron containing indole side chain of l-Trp in peptide 14 completes the formation of a hydrophobic cluster and results in 90 % folding, the folded fraction is significantly decreased to approximately 30 % for the 6 π electron l-Hop side chain in peptide 16. Metal chelation of Ga3+ reconstitutes the folding of 16 to above 60 % due to the formation of the Ga(16)3 trimer. The chelation process of 16 is monitored by NMR spectroscopy and the subsequent release of Ga3+ by a competitive metal chelator exemplifies the reversible oligomerization of peptide epitopes by metal chelation, bearing the opportunity to synthesize protein-sized aggregates on the basis of reversible chemistry in water.
- Reutzel, Jan,Diogo, Timm M.,Geyer, Armin
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supporting information
p. 8450 - 8456
(2017/06/28)
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- NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS
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The invention relates to novel heteroaryl and heterocycle compounds of formula I and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune diseases and cancer.
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Paragraph 230
(2016/08/23)
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- NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS
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The invention relates to novel heteroaryl and heterocycle compounds and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3k and for treating inflammatory and autoimmune disorders diseases and cancer.
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Page/Page column 109; 110
(2014/02/16)
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- NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITION AND METHODS THEREOF
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Disclosed are novel heteroaryl and heterocycle compounds of formula I-1, I-2 or I-3 and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune diseases and cancer.
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Page/Page column 136; 137
(2014/02/16)
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- NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITIONS AND METHODS
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Provided are novel heteroaryl and heterocycle compounds of formula (I-1), (I-2) or (I-3) and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune disorders diseases and cancer.
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Page/Page column 138
(2014/02/16)
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- BARETTIN AND DERIVATIVES THEREOF FOR MEDICAL USE, IN PARTICULAR FOR THE TREATMENT OF DISEASES RELATED TO OXIDATIVE STRESS OR INFLAMMATION, AND FOR PRESERVING OR WASHING ORGANS
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The present invention relates to compounds of formula(I) herein, which includes barettin and derivatives thereof, or any pharmaceutically acceptable salt thereof for use as a medicament. Further the present invention relates to same compounds for use in t
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Page/Page column 22
(2014/10/18)
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- SUBSTITUTED HETEROCYCLIC ACETAMIDES AS KAPPA OPIOID RECEPTOR (KOR) AGONISTS
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The present invention relates to a series of substituted compounds having the general formula (I), including their ste reoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3. R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
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Page/Page column 109
(2013/09/26)
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- Synthesis, anticonvulsant activity, and neuropathic pain-attenuating activity of N-benzyl 2-amino-2-(hetero)aromatic acetamides
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N-Benzyl 2-acetamido-2-substituted acetamides, where the 2-substituent is a (hetero)aromatic moiety, are potent anticonvulsants. We report the synthesis and whole animal pharmacological evaluation of 16 analogues where the terminal 2-acetyl group was removed to give the corresponding primary amino acid derivatives (PAADs). Conversion to the PAAD structure led to a substantial drop in seizure protection in animal tests, demonstrating the importance of the N-acetyl moiety for anticonvulsant activity. However, several of the PAADs displayed notable pain-attenuating activities in a mouse model.
- Baruah, Pranjal K.,Dinsmore, Jason,King, Amber M.,Salomé, Christophe,De Ryck, Marc,Kaminski, Rafal,Provins, Laurent,Kohn, Harold
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supporting information; experimental part
p. 3551 - 3564
(2012/07/28)
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- Efficient synthesis of DOPA analogues in pepticinnamins E via asymmetric catalytic hydrogenation of dehydroamino esters
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One practical synthetic procedure with five steps was developed to prepare a series of N-protected-2-(diethoxyphosphoryl)glycinates with good yields, which was treated with aldehydes under mild condition to give different dehydroamino esters with high yields and excellent Z/E selectivity. The subsequently homogeneous enantioselective hydrogenation of the dehydroamino esters affords a series of new DOPA analogues.
- Sun, De-Qun,Sun, Li,Luo, Min
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scheme or table
p. 1731 - 1734
(2012/08/28)
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- Scalable synthesis of the desoxy-biphenomycin B core
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We describe the evolution of a kilogram-scale synthesis of the protected cyclic tripeptide desoxy-biphenomycin B, based on an early discovery route. The retrosynthetic concept included a macrolactamization strategy to build the core ring system of biphenomycin B in combination with a double catalytic asymmetric hydrogenation protocol for the construction of the ansa-tripeptide precursor. Eventually, the kilogram process comprised a 16-step sequence with an overall yield for the longest linear sequence of 19.5%.
- Berwe, Mathias,Joentgen, Winfried,Krueger, Jochen,Cancho-Grande, Yolanda,Lampe, Thomas,Michels, Martin,Paulsen, Holger,Raddatz, Siegfried,Weigand, Stefan
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experimental part
p. 1348 - 1357
(2012/01/12)
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- Merging the structural motifs of functionalized amino acids and α-Aminoamides: Compounds with Significant Anticonvulsant Activities
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Functional amino acids (FAAs) and α-aminoamides (AAAs) are two classes of antiepileptic drugs (AEDs) that exhibit pronounced anticonvulsant activities. We combined key structural pharmacophores present in FAAs and AAAs to generate a new series of compounds and document that select compounds exhibit activity superior to either the prototypical FAA (lacosamide) or the prototypical AAA (safinamide) in the maximal electroshock (MES) seizure model in rats. A representative compound, (R)-N-4′-((3′′-fluoro) benzyloxy)benzyl 2-acetamido-3-methoxypropionamide ((R)-10), was tested in the MES (mice, ip), MES (rat, po), psychomotor 6 Hz (32 mA) (mice, ip), and hippocampal kindled (rat, ip) seizure tests providing excellent protection with ED50 values of 13, 14, ~10 mg/kg, and 12 mg/kg, respectively. In the rat sciatic nerve ligation model (ip), (R)-10 (12 mg/kg) provided an 11.2-fold attenuation of mechanical allodynia. In the mouse biphasic formalin pain model (ip), (R)-10 (15 mg/kg) reduced pain responses in the acute and the chronic inflammatory phases.
- Salomé, Christophe,Salomé-Grosjean, Elise,Stables, James P.,Kohn, Harold
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supporting information; experimental part
p. 3756 - 3771
(2010/07/16)
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- Efficient total synthesis of (-)-kaitocephalin
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A highly dlastereoselectlve total synthesis of (-)-kaltocephalln, a novel antagonist of lonotroplc glutamate receptors, was accomplished In 12 steps starting from 5-substltuted proline ester via the aldol reaction with OBO-serlne aldehyde, (E)-selectlve α,β-dehydroamlno acid synthesis using a new HWE reagent, and catalytic hydrogenation.
- Hamada, Makoto,Shinada, Tetsuro,Ohfune, Yasufumi
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supporting information; experimental part
p. 4664 - 4667
(2009/12/24)
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- Stereocontrolled total synthesis of (-)-kaitocephalin
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(Chemical Equation Presented) This paper describes the successful implementation of a stereocontrolled strategy for the total chemical synthesis of the pyrrolidine-based alkaloid (-)-kaitocephalin. This scalable synthetic route profits from the strategic
- Vaswani, Rishi G.,Chamberlin, A. Richard
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p. 1661 - 1681
(2008/09/18)
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- Azabicycloalkenes as synthetic intermediates: Application to the preparation of diazabicycloalkane scaffolds
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A general method to synthesize bicyclic dipeptide mimetics is reported. Key intermediates are azabicycloalkenes 9 and 17, which are prepared via Diels-Alder reactions and subsequent mild deprotection. These unsaturated bicyclic heterocycles are versatile
- Prenzel, Alexander H. G. P.,Deppermann, Nina,Maison, Wolfgang
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p. 1681 - 1684
(2007/10/03)
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- A facile synthesis of α-amino-DOTA as a versatile molecular imaging probe
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An amino group has been introduced into one ligand of DOTA that can couple to peptidyl carboxylates by coupling α-brominated glycine to DO3A-tBu (1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid, tert-butylester)). α-Amino-DOTA was coupled
- Yoo, Byunghee,Pagel, Mark D.
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p. 7327 - 7330
(2007/10/03)
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- The efficient direct synthesis of N,O-acetal compounds as key intermediates of discorhabdin A: Oxidative fragmentation reaction of α-amino acids or β-amino alcohols by using hypervalent iodine(III) reagents
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Hypervalent iodine(III) reagents are readily available, easy to handle, and have a low toxicity and similar reactivities to those of heavy metal reagents, and hence they are used for various oxidative reactions. The oxidative cleavage of alkynes or carbon
- Harayama, Yu,Yoshida, Masako,Kamimura, Daigo,Wada, Yasufumi,Kita, Yasuyuki
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p. 4893 - 4899
(2008/02/08)
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- C-linked galactosyl serine AFGP analogues as potent recrystallization inhibitors
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(Chemical Equation Presented) A series of C-linked antifreeze glycoprotein analogues have been prepared to evaluate antifreeze activity as a function of distance between the carbohydrate moiety and polypeptide backbone. The building blocks for these analogues were prepared using either an olefin cross-metathesis or catalytic asymmetric hydrogenation. Analysis of antifreeze protein-specific activity revealed that only analogue 2a (n = 1) was a potent recrystallization inhibitor and thus has potential medical and industrial applications.
- Liu, Suhuai,Ben, Robert N.
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p. 2385 - 2388
(2007/10/03)
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- COMPOUNDS HAVING BOTH α7 NICOTINIC AGONIST ACTIVITY AND 5HT3 ANTAGONIST ACTIVITY FOR TREATMENT OF CNS DISEASES
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The invention discloses compounds that are selective α7 nAChR agonists and 5-HT3 antagonists. The compounds are useful for treating many CNS diseases.
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- Total synthesis of isoroquefortine C
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A short and efficient total synthesis of isoroquefortine C, the 3,12-(Z)-isomer of roquefortine C, from L-tryptophan methyl ester hydrochloride and 4(5)-(hydroxy)methylimidazole hydrochloride is described.
- Schiavi, Bruno M.,Richard, David J.,Joullie, Madeleine M.
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p. 620 - 624
(2007/10/03)
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- Peptidomimetic of helix-turn-helix or gamma-turn
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A peptidomimetic of the turn in the helix-turn-helix (HTH) motif of DNA-binding proteins was designed and synthesized. Conformational constraint was achieved by an unusual linking of two amino acids with a side-chain carbon--carbon bond. A phenyl ring pro
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- Preparation of protected α-alkoxyglycines
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N-Carbobenzoxy-α-alkoxyglycine esters were synthesized by H2SO4-catalyzed O-alkylation of N-carbobenzoxy-α-hydroxyglycine and also by base treatment of N-carbobenzoxy-N-chloroglycine methyl ester in the corresponding alcohol. Saponification of the protected α-alkoxyglycines gave free acids which can be used for the synthesis of α-alkoxyglycine residue-containing peptides.
- Kawai, Masao,Hosoda, Kouji,Omori, Yoshimasa,Yamada, Keiichi,Hayakawa, Shoko,Yamamura, Hatsuo,Butsugan, Yasuo
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p. 1545 - 1554
(2007/10/03)
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- A convenient synthesis of 2-(diethoxyphosphonyl)glycine and its derivatives
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A simple and very efficient method for the preparation of 2-(diethoxyphosphonyl)glycine and its N-methyl analog as the free acids is described and their conversion to the corresponding t-butyl esters demonstrated.
- Shankar,Scott
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p. 231 - 234
(2007/10/02)
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- Preparation of Protected α-Methoxyglycine and Its Incorporation into Peptide Synthesis
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A protected α-methoxyglycine Cbz-DL-Gly(OMe)-OMe (1) was prepared from the N-chloro derivative of Cbz-Gly-OMe.Catalytic hydrogenolysis of 1 in the presence of a mixed anhydride prepared from a Boc-amino acid and ClCO2Bui gave a diastereomeric p
- Kawai, Masao,Neogi, Partha,Khattri, Parth S.,Butsugan, Yasuo
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p. 577 - 580
(2007/10/02)
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- General Synthesis of β,γ-Alkynylglycine Derivatives
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The coupling of α-haloglycinates 8 with alkynyltin reagents produces the fully protected β,γ-alkynylglycines 9.Subsequent deprotection of the amino or carboxyl groups generates differentially protected β,γ-alkynylglycine derivatives 10-14.The free amino a
- Williams, Robert M.,Aldous, David J.,Aldous, Suzanne C.
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p. 4657 - 4663
(2007/10/02)
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- FACILE SYNTHESIS OF α-PHOSPHORYLATED α-AMINO ACIDS
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Various α-phosphorylated α-amino acid derivatives were synthesized conveniently by the reaction of methyl α-methoxyhippurate and methyl α-methoxy-N-benzyloxycarbonyl-glycinate with phosphites under the Lewis acid.Hydrolysis of (12) with TMSI gave 2-phosph
- Ku, Bonchul,Oh, Dong Young
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p. 4465 - 4466
(2007/10/02)
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- Process for preparing substituted glycines
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A new process is disclosed for the preparation of N-acyl-α-aromatic and N-acyl-α-heteroaromatic glycines by reaction of an α-ester or ether of an N-acylglycine ester or acid with an aromatic or heteroaromatic compound. Also disclosed are new intermediates for preparing N-acyl-α-aromatic and N-acyl-α-heteroaromatic glycines.
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