87936-34-3Relevant academic research and scientific papers
GLP-1 RECEPTOR MODULATORS
-
, (2016/06/28)
Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "^^^^" represents either or both the R and S form of the compound) (I) where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.
A versatile approach to noncoded β-hydroxy-α-amino esters and α-amino acids/esters from morita-baylis-hillman adducts
Ullah, Hamid,Ferreira, Andr V.,Bendassolli, Jos A.,Rodrigues, Manoel T.,Formiga, Andr Luiz B.,Coelho, Fernando
, p. 113 - 123 (2015/02/02)
A simple and straightforward approach to the diastereoselective synthesis of noncoded β-hydroxy-α-amino esters from Morita-Baylis-Hillman (MBH) adducts is described. The strategy is based on a one-pot sequence involving an oxidative cleavage of the double bond of silylated Morita-Baylis-Hillman adducts, followed by the reaction with hydroxylamine hydrochloride/pyridine to form oximes. The stereoselective reduction of the oximes with the mixture MoCl5·nH2O/NaBH3CN led to the corresponding anti-β-hydroxy-α-amino esters in four steps in good overall yield and with diastereoselectivity higher than 95%. A slight modification of the synthetic approach has allowed for the racemic synthesis of a set of noncoded α-amino esters/acids and DOPA
Asymmetric synthesis of 2,4,5-trisubstituted Δ2- thiazolines
Bengtsson, Christoffer,Nelander, Hanna,Almqvist, Fredrik
, p. 9916 - 9922 (2013/08/23)
Δ2-Thiazolines are interesting heterocycles that display a wide variety of biological characteristics. They are also common in chiral ligands used for asymmetric syntheses and as synthetic intermediates. Herein, we present asymmetric routes to
Diastereo- and enantioselective hydrogenation of α-amino-β-keto ester hydrochlorides catalyzed by an iridium complex with MeO-BIPHEP and NaBArF: Catalytic cycle and five-membered chelation mechanism of asymmetric hydrogenation
Maeda, Tsukuru,Makino, Kazuishi,Iwasaki, Masamichi,Hamada, Yasumasa
supporting information; experimental part, p. 11954 - 11962 (2011/01/12)
The development of Ir-catalyzed asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides is described. This reaction proceeds through a dynamic kinetic resolution to produce anti-β-hydroxy- α-amino acid esters in a high diastereo- and enantioselective manner. Mechanistic studies have revealed that this unique asymmetric hydrogenation proceeds through reduction of the ketone moiety via the five-membered transition state involving the chelation between the oxygen of the ketone and the nitrogen of the amine function. The relationship studies between the hydrogen pressure and the stereoselectivity have disclosed two mechanisms dependent on hydrogen pressure. Under low hydrogen pressure (15 atm), the reaction rate proportionally increased with the hydrogen pressure. However, under the high hydrogen conditions, the reaction rate exponentially accelerated along with the increasing hydrogen pressure, which suggests the participation of two or more of hydrogen atoms. Apply some pressure: The Ir-catalyzed asymmetric hydrogenation of α-amino-β-keto ester hydrochlorides proceeds through a dynamic kinetic resolution to produce anti-β-hydroxy-α-amino acid esters in a high diastereo- and enantioselective manner (see scheme). Mechanistic studies revealed that this unique asymmetric hydrogenation proceeds through reduction of the ketone moiety via the five-membered transition state.
Addition of azomethine ylides to aldehydes: Mechanistic dichotomy of differentially substituted α-imino esters
Seashore-Ludlow, Brinton,Torssell, Staffan,Somfai, Peter
scheme or table, p. 3927 - 3933 (2010/09/18)
The formal 1,3-dipolar cycloaddition of azomethine ylides and aldehydes is explored, as hydrolysis of the resulting oxazolidine product gives facile access to valuable syn-β-arylβ-hydroxy-α-amino esters. The use of using benzaldehydederived imines as the ylide precursor results in 1,3-dipolar cycloaddition with high conversions but low diastereoselec-tivity. In contrast, the employment of benzophenone-derived imines as the ylide precursor results in an aldol reaction, which gives the intermediate oxazolidine in high diastereoselectivity and requires a weak acid catalyst to achieve higher conversions.
Stereoselective synthesis of β-hydroxyphenylalanines using imino 1,2-Wittig rearrangement of hydroximates
Miyata, Okiko,Asai, Hiroshi,Naito, Takeaki
, p. 355 - 360 (2007/10/03)
The imino 1,2-Wittig rearrangement of hydroximates containing a furan ring provides a novel method for the synthesis of β-hydroxy-α-amino acids. Upon treatment with LDA, hydroximates smoothly underwent the rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into both cis- and trans-oxazolidinones with high stereoselectivity. The cis- and trans-oxazolidinones were stereoselectively converted into erythro- and thereo-β-hydroxypheny lalanines, respectively, via the oxidative cleavage of a furan ring, ring-opening of oxazolidinone, and deprotection.
Catalytic enantio- and diastereoselective aldol reactions of glycine-derived silicon enolate with aldehydes: An efficient approach to the asymmetric synthesis of anti-β-hydroxy-α-amino acid derivatives
Kobayashi, Jun,Nakamura, Masayuki,Mori, Yuichiro,Yamashita, Yasuhiro,Kobayashi, Shu
, p. 9192 - 9193 (2007/10/03)
We have developed an efficient method for the asymmetric synthesis of anti-β-hydroxy-α-amino acid derivatives based on highly enantio- and diastereoselective aldol reactions of the silicon enolate derived from N-trifluoroacetylglycinate with aldehydes using a chiral zirconium catalyst. The resulting N-trifluoroacetyl group is easily cleaved under either acidic or basic conditions and can be used directly as a protecting group for further transformations. Copyright
Synthesis of all stereoisomers and some congeners of isocytoxazone
Hamer?ak, Zdenko,?epac, Dragan,?iher, Dinko,?unji?, Vitomir
, p. 375 - 382 (2007/10/03)
cis-Isocytoxazone 2a and trans-isocytoxazone 2b, structural isomers of the antiasthmatic agent cytoxazone (-)-1, and their 5-substituted congeners 23-28 have been prepared. Aldol reaction of para-substituted benzaldehydes with 7-chloro-1-methyl-5-phenyl-1,4-benzodiazepin-2-one, followed by separation of diastereomeric racemates afforded 3-10. Acid-catalyzed 1,4-benzodiazepine ring opening, and transformation of the methyl esters of β-aryl-β-hydroxy-α-amino acids (11-16) via 4-methoxycarbonyl derivatives of 1,3-oxazolidin-2-one (17-22) and their reduction afforded the target oxazolidin-2-one derivatives 23-28. Racemic isocytoxazones 2a and 2b were prepared by an independent route starting from 4-methoxystyrene epoxide. Pure enantiomers of these diastereomeric racemates were separated by HPLC chromatography on chiral stationary phases. Their CD spectra, along with those of previously prepared enantiomers of cis-cytoxazone 1a and trans-cytoxazone 1b are discussed.
Peptide inhibitors of CDK2-cyclin A that target the cyclin recruitment-Site: Structural variants of the C-Terminal Phe
Atkinson, Gail E.,Cowan, Angela,McInnes, Campbell,Zheleva, Daniella I.,Fischer, Peter M.,Chan, Weng C.
, p. 2501 - 2505 (2007/10/03)
A focused series of octapeptides based on the lead compound H-His-Ala-Lys-Arg-Arg-Leu-Ile-Phe-NH2 1, in which the C-terminal phenylalanine residue was replaced by α and/or β-modified variants, was synthesized using solid-phase chemistry. Both the L-threo-β-hydroxy-phenylalanine (β-phenylserine, Pse) and (2S)-phenylalaninol derivatives, as competitive binders at the cyclin-recruitment site, displayed potent inhibitory activity towards the CDK2-cyclin A complex. Unexpectedly, the D-threo-Pse derivatives also showed inhibitory activity.
Asymmetric Synthesis via Heterocyclic Intermediates, XLV. Asymmetric Synthesis of Diastereomerically and Enantiomerically Pure 3-Substituted (2R,3S)-Serine Methyl Esters
Beulshausen, Tessa,Groth, Ulrich,Schoellkopf, Ulrich
, p. 1207 - 1209 (2007/10/02)
The titanium derivative 2 of the bislactim ether 1 of cyclo(-L-Val-Gly-) reacts with aldehydes and ketones 3 highly diastereoselectively to give the syn-addition products 4.Upon hydrolysis with diluted trifluoroacetic acid the compounds 4 yield besides me
