10568-38-4Relevant articles and documents
Eleven amino acid glucagon-like peptide-1 receptor agonists with antidiabetic activity
Mapelli, Claudio,Natarajan, Sesha I.,Meyer, Jean-Philippe,Bastos, Margarita M.,Bernatowicz, Michael S.,Lee, Ving G.,Pluscec, Jelka,Riexinger, Douglas J.,Sieber-McMaster, Ellen S.,Constantine, Keith L.,Smith-Monroy, Constance A.,Golla, Rajasree,Ma, Zhengping,Longhi, Daniel A.,Shi, Dan,Xin, Li,Taylor, Joseph R.,Koplowitz, Barry,Chi, Cecilia L.,Khanna, Ashish,Robinson, Gordon W.,Seethala, Ramakrishna,Antal-Zimanyi, Ildiko A.,Stoffel, Robert H.,Han, Songping,Whaley, Jean M.,Huang, Christine S.,Krupinski, John,Ewing, William R.
, p. 7788 - 7799 (2009)
Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acidGLP-1 receptor agonists. These peptides consist of a structurally optimized 9- mer, which is closely related to the N-terminal 9 amino acids ofGLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.
Coupling of Reformatsky Reagents with Aryl Chlorides Enabled by Ylide-Functionalized Phosphine Ligands
Hu, Zhiyong,Wei, Xiao-Jing,Handelmann, Jens,Seitz, Ann-Katrin,Rodstein, Ilja,Gessner, Viktoria H.,Goo?en, Lukas J.
supporting information, p. 6778 - 6783 (2021/02/01)
The coupling of aryl chlorides with Reformatsky reagents is a desirable strategy for the construction of α-aryl esters but has so far been substantially limited in the substrate scope due to many challenges posed by various possible side reactions. This limitation has now been overcome by the tailoring of ylide-functionalized phosphines to fit the requirements of Negishi couplings. Record-setting activities were achieved in palladium-catalyzed arylations of organozinc reagents with aryl electrophiles using a cyclohexyl-YPhos ligand bearing an ortho-tolyl-substituent in the backbone. This highly electron-rich, bulky ligand enables the use of aryl chlorides in room temperature couplings of Reformatsky reagents. The reaction scope covers diversely functionalized arylacetic and arylpropionic acid derivatives. Aryl bromides and chlorides can be converted selectively over triflate electrophiles, which permits consecutive coupling strategies.
Mechanism of the Bis(imino)pyridine-Iron-Catalyzed Hydromagnesiation of Styrene Derivatives
Neate, Peter G. N.,Greenhalgh, Mark D.,Brennessel, William W.,Thomas, Stephen P.,Neidig, Michael L.
, p. 10099 - 10108 (2019/07/04)
Iron-catalyzed hydromagnesiation of styrene derivatives offers a rapid and efficient method to generate benzylic Grignard reagents, which can be applied in a range of transformations to provide products of formal hydrofunctionalization. While iron-catalyzed methodologies exist for the hydromagnesiation of terminal alkenes, internal alkynes, and styrene derivatives, the underlying mechanisms of catalysis remain largely undefined. To address this issue and determine the divergent reactivity from established cross-coupling and hydrofunctionalization reactions, a detailed study of the bis(imino)pyridine iron-catalyzed hydromagnesiation of styrene derivatives is reported. Using a combination of kinetic analysis, deuterium labeling, and reactivity studies as well as in situ 57Fe M?ssbauer spectroscopy, key mechanistic features and species were established. A formally iron(0) ate complex [iPrBIPFe(Et)(CH2a?CH2)]- was identified as the principle resting state of the catalyst. Dissociation of ethene forms the catalytically active species which can reversibly coordinate the styrene derivative and mediate a direct and reversible β-hydride transfer, negating the necessity of a discrete iron hydride intermediate. Finally, displacement of the tridentate bis(imino)pyridine ligand over the course of the reaction results in the formation of a tris-styrene-coordinated iron(0) complex, which is also a competent catalyst for hydromagnesiation.
ortho-Difunctionalization of arynes by LiZnEt2(TMP)-mediated deprotonative zincation/elimination of aryl triflates
Cho, Seoyoung,Wang, Qiu
supporting information, p. 3325 - 3328 (2018/04/02)
Generation of arynes from aryl triflates has been achieved using lithium diethyl(tetramethylpiperidyl)-zincate base LiZnEt2(TMP), via a directed ortho-deprotonative zincation and subsequent elimination of the triflate group. The aryne formation
