- Enantioselective synthesis of 4-substituted phenylalanines by cross- coupling reactions
-
The enantiomerically enriched BOC-protected (4- pinacolylborono)phenylalanine methyl ester (8) is produced via enzymatic resolution of the racemic material, or direct synthesis from the corresponding iodide (or triflate), and undergoes Suzuki-Miyaura coup
- Firooznia,Gude,Chan,Marcopulos,Satoh
-
-
Read Online
- Synthesis of Enantiopure Unnatural Amino Acids by Metallaphotoredox Catalysis
-
We describe herein a two-step process for the conversion of serine to a wide array of optically pure unnatural amino acids. This method utilizes a photocatalytic cross-electrophile coupling between a bromoalkyl intermediate and a diverse set of aryl halides to produce artificial analogues of phenylalanine, tryptophan, and histidine. The reaction is tolerant of a broad range of functionalities and can be leveraged toward the scalable synthesis of valuable pharmaceutical scaffolds via flow technology.
- Agejas, Javier,Barberis, Mario,De Frutos, Oscar,Faraggi, Tomer M.,García-Cerrada, Susana,MacMillan, David W. C.,Mateos, Carlos,Rincón, Juan A.,Rouget-Virbel, Caroline
-
p. 1966 - 1973
(2021/08/18)
-
- Rhodium-Catalyzed Dealkenylative Arylation of Alkenes with Arylboronic Compounds
-
The C?C bond formation reaction represents a fundamental and important transformation in synthetic chemistry, and exploring new types of C?C bond formation reactions is recognized as appealing, yet challenging. Herein, we disclose the first example of rhodium-catalyzed dealkenylative arylation of alkenes with arylboronic compounds, thereby providing an unconventional access to bi(hetero)aryls with excellent chemoselectivity. In this method, C(aryl)?C(alkenyl) and C(alkenyl)?C(alkenyl) bonds in various alkenes and 1,3-dienes can be cleaved via a hydrometalation and followed by β-carbon elimination pathway for Suzuki–Miyaura reactions. Furthermore, a series of novel organic fluorescent molecules with excellent photophysical properties has been efficiently constructed with this protocol.
- Das, Mowpriya,Glorius, Frank,Maisuls, Iván,Strassert, Cristian A.,Tan, Guangying
-
p. 15650 - 15655
(2021/06/08)
-
- ANTIMICROBIAL COMPOUNDS AND METHODS
-
The invention is directed to compounds that are active as antibacterial agents. The invention compounds are active against gram-positive and gram-negative bacteria and can be used to treat infections caused by gram-positive and gram-negative bacteria. Also disclosed are processes and intermediates for making the compounds.
- -
-
-
- Process Development of Tryptophan Hydroxylase Inhibitor LX1031, a Drug Candidate for the Treatment of Irritable Bowel Syndrome
-
Two process routes for LX1031, a tryptophan hydroxylase inhibitor for the treatment of irritable bowel syndrome, were developed. They shared the same left-hand and right-hand starting materials as well as the penultimate intermediate. The chiral center in
- Bednarz, Mark S.,Iimura, Shinya,Kanamarlapudi, Ramanaiah C.,Lim, Ngiap-Kie,Wu, Wenxue,Yan, Jie,Zhang, Haiming,Zhao, Matthew M.
-
p. 261 - 273
(2020/03/10)
-
- P(III)/P(V)-Catalyzed Methylamination of Arylboronic Acids and Esters: Reductive C-N Coupling with Nitromethane as a Methylamine Surrogate
-
The direct reductive N-arylation of nitromethane by organophosphorus-catalyzed reductive C-N coupling with arylboronic acid derivatives is reported. This method operates by the action of a small ring organophosphorus-based catalyst (1,2,2,3,4,4-hexamethylphosphetane P-oxide) together with a mild terminal reductant hydrosilane to drive the selective installation of the methylamino group to (hetero)aromatic boronic acids and esters. This method also provides for a unified synthetic approach to isotopically labeled N-methylanilines from various stable isotopologues of nitromethane (i.e., CD3NO2, CH315NO2, and 13CH3NO2), revealing this easy-to-handle compound as a versatile precursor for the direct installation of the methylamino group.
- Li, Gen,Qin, Ziyang,Radosevich, Alexander T.
-
p. 16205 - 16210
(2020/10/26)
-
- Solid-phase synthesis of biaryl bicyclic peptides containing a 3-aryltyrosine or a 4-arylphenylalanine moiety
-
A methodology for the solid-phase synthesis of biaryl bicyclic peptides containing a Phe-Phe, a Phe-Tyr or a Tyr-Tyr motif has been devised. This approach comprises two key steps. The first one involves the cyclization of a linear peptidyl resin containing the corresponding halo- and boronoamino acids via a microwave-assisted Suzuki–Miyaura cross coupling. This step is followed by the macrolactamization of the resulting biaryl monocyclic peptidyl resin leading to the formation of the expected biaryl bicyclic peptide. This study provides the first solid-phase synthesis of this type of bicyclic compounds being amenable to prepare a diversity of synthetic or natural biaryl bicyclic peptides.
- Ng-Choi, Iteng,Oliveras, àngel,Feliu, Lidia,Planas, Marta
-
p. 761 - 768
(2019/04/17)
-
- Sequence Programming with Dynamic Boronic Acid/Catechol Binary Codes
-
The development of a synthetic code that enables a sequence programmable feature like DNA represents a key aspect toward intelligent molecular systems. We developed herein the well-known dynamic covalent interaction between boronic acids (BAs) and catechols (CAs) into synthetic nucleobase analogs. Along a defined peptide backbone, BA or CA residues are arranged to enable sequence recognition to their complementary strand. Dynamic strand displacement and errors were elucidated thermodynamically to show that sequences are able to specifically select their partners. Unlike DNA, the pH dependency of BA/CA binding enables the dehybridization of complementary strands at pH 5.0. In addition, we demonstrate the sequence recognition at the macromolecular level by conjugating the cytochrome c protein to a complementary polyethylene glycol chain in a site-directed fashion.
- Hebel, Marco,Riegger, Andreas,Zegota, Maksymilian M.,Kizilsavas, G?nül,Ga?anin, Jasmina,Pieszka, Michaela,Lückerath, Thorsten,Coelho, Jaime A. S.,Wagner, Manfred,Gois, Pedro M. P.,Ng, David Y. W.,Weil, Tanja
-
supporting information
p. 14026 - 14031
(2019/10/11)
-
- INTEGRIN ANTAGONISTS
-
The present disclosure provides therapeutic agents including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such therapeutic agents. Methods of using the therapeutic agents are also provided.
- -
-
-
- SULFONAMIDE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
-
Provided is a sulfonamide derivative represented by the following general formula (1) and having an α4 integrin inhibitory effect with high selectivity with a low effect on α4β1 and a high effect on α4β7, or a pharmaceutically acceptable salt thereof (in the general formula (1), A, B, D, E, R41, and a to h are as described in the description).
- -
-
-
- N-SUBSTITUTED 3,3'-(BIPHENYL-4,4'-DIYL)BIS-2-AMINOPROPANENITRILES AS DPPI INHIBITORS
-
The invention relates to a compound of Formula (I) and its use as a selective dipeptidyl peptidase I inhibitor, as well as pharmaceutical compositions comprising said compound, and methods of treatment involving said compounds.
- -
-
-
- SULFONAMIDE DERIVATIVE AND MEDICINAL USE THEREOF
-
Provided are sulfonamide derivatives of a specific chemical structure in which a sulfonamide group having, as a substituent, a phenyl group or a heterocyclic group having a hetero atom(s) as a constituent element(s) is present at its terminal, and pharmaceutically acceptable salts thereof. These compounds are novel compounds having excellent α4 integrin-inhibitory action.
- -
-
-
- Palladium-catalyzed difluoroalkylation of aryl boronic acids: A new method for the synthesis of aryldifluoromethylated phosphonates and carboxylic acid derivatives
-
The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF2PO(OEt) 2, ArCF2CO2Et, and ArCF2CONR 1R2) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle. Palladium does it: The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed (see scheme). Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle. Copyright
- Feng, Zhang,Min, Qiao-Qiao,Xiao, Yu-Lan,Zhang, Bo,Zhang, Xingang
-
p. 1669 - 1673
(2014/03/21)
-
- PROCESS FOR THE PREPARATION OF SUBSTITUTED PHENYLALANINES
-
Intermediates and synthetic processes for the preparation of substituted phenylalanine-based compounds are disclosed.
- -
-
-
- Functionalization of aromatic amino acids via direct C-H activation: Generation of versatile building blocks for accessing novel peptide space
-
Functionalized α-amino acid building blocks have been prepared in good yield with high regiocontrol and preservation of stereochemistry via iridium-catalyzed borylation of suitably protected aromatic α-amino acid derivatives. The utility of these systems
- Meyer, Falco-Magnus,Liras, Spiros,Guzman-Perez, Angel,Perreault, Christian,Bian, Jianwei,James, Keith
-
supporting information; experimental part
p. 3870 - 3873
(2010/11/05)
-
- Palladium-catalyzed borylation of l-tyrosine triflate derivative with pinacolborane: practical route to 4-borono-l-phenylalanine (l-BPA) derivatives
-
Efficient palladium-catalyzed borylation of protected l-tyrosine triflate with pinacolborane was achieved despite previous reports to the contrary. In addition to the use of an inexpensive boron source, the reaction was carried out in the presence of only 0.5 mol % palladium catalyst. Furthermore, the borylation can be performed using pinacolborane prepared in situ from pinacol and borane-diethylaniline complex. This represents a practical entry to 4-borono-l-phenylalanine (l-BPA) derivatives.
- Iimura, Shinya,Wu, Wenxue
-
supporting information; experimental part
p. 1353 - 1355
(2010/05/03)
-
- PROCESS FOR THE PREPARATION OF SUBSTITUTED PHENYLALANINES
-
Intermediates and synthetic processes for the preparation of substituted phenylalanine-based compounds (e.g., of Formula I) are disclosed:
- -
-
Page/Page column 26
(2010/05/13)
-
- Process for the preparation of substituted phenylalanines
-
Intermediates and synthetic processes for the preparation of substituted phenylalanine-based compounds (e.g., of Formula I) are disclosed:
- -
-
Page/Page column 9; 12-13
(2009/03/07)
-
- METHODS OF PREPARING 4-PHENYL-6-(2,2,2-TRIFLUORO-1-PHENYLETHOXY)PYRIMIDINE-BASED COMPOUNDS
-
Methods useful for preparing compounds of formula I: and salts thereof are disclosed. Also disclosed are intermediates useful in the preparation of such compounds.
- -
-
Page/Page column 8
(2009/04/24)
-
- SOLID FORMS OF (S)-ETHYL 2-AMINO-3-(4-(2-AMINO-6-((R)-1-(4-CHLORO-2-(3-METHYL-1H-PYRAZOL-1-YL)PHENYL)-2,2,2-TRIFLUOROETHOXY)-PYRIMIDIN-4-YL)PHENYL)PROPANOATE AND METHODS OF THEIR USE
-
Solid forms of (S)-ethyl 2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoate and salts thereof are disclosed.
- -
-
Page/Page column 5
(2009/04/24)
-
- SOLID FORMS OF (S)-2-AMINO-3-(4-(2-AMINO-6-((R)-2,2,2-TRIFLUORO-1-(3'-METHOXYBIPHENYL- 4-YL)ETHOXY)PYRIMIDIN-4-YL)PHENYL) PROPANOIC ACID AND METHODS OF THEIR USE
-
Solid forms of (S)-2-amino-3-(4-(2-amino-6-((R)-2,2,2-trifluoro-1-(3'-methoxybiphenyl-4-yl)ethoxy)pyrimidin-4-yl)phenyl)propanoic acid and salts thereof are disclosed
- -
-
Page/Page column 6
(2009/04/24)
-
- NOVEL PHENYLALANINE DERIVATIVE
-
Phenylalanine derivatives of the following formula, analogues thereof and pharmaceutically acceptable salts thereof have an antagonistic activity to α4 integrin. They are used as therapeutic agents or preventive agents for various diseases concerning α4 i
- -
-
-
