67249-02-9Relevant academic research and scientific papers
Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- A nd Piperidine-Free Knoevenagel-Doebner Condensation
Hardegger, Leo A.,Humair, Roger,Sidler, Eric
, p. 1756 - 1762 (2020/10/26)
During route scouting for EMA401 (1), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel-Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.
Ultrastrong, Transparent Polytruxillamides Derived from Microbial Photodimers
Tateyama, Seiji,Masuo, Shunsuke,Suvannasara, Phruetchika,Oka, Yuuki,Miyazato, Akio,Yasaki, Katsuaki,Teerawatananond, Thapong,Muangsin, Nongnuj,Zhou, Shengmin,Kawasaki, Yukie,Zhu, Longbao,Zhou, Zhemin,Takaya, Naoki,Kaneko, Tatsuo
, p. 3336 - 3342 (2016/06/01)
Ultrastrong and transparent bioplastics are generated from fermented microbial monomers. An exotic aromatic amino acid, 4-aminocinnamic acid, was prepared from a biomass using recombinant bacteria, and quantitatively photodimerized, and diacid and diamino monomers that were both characterized by a rigid α-truxillate structure were generated. These two monomers were polycondensed to create the polyamides with a phenylenecyclobutane repeating backbone such as poly{(4,4′-diyl-α-truxillic acid dimethyl ester) 4,4′-diacetamido-α-truxillamide} which was processed into amorphous fibers and plastic films having high transparency. In spite of noncrystalline structure, mechanical strength of the fiber is 407 MPa at maximum higher than those of other transparent plastics and borosilicate glasses, presumably due to the tentative molecular spring function of the phenylenecyclobutanyl backbone.
POLYMER RAW MATERIAL AND POLYMER MATERIAL
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Paragraph 0078; 0079; 0080; 0081, (2014/11/11)
To provide a polymer material having properties that allow the polymer material to replace a polyimide and a polyamide synthesized from a petroleum raw material, said polymer material being synthesized from a raw material derived from natural molecules. [
β-alanine-DBU: A highly efficient catalytic system for knoevenagel-doebner reaction under mild conditions
Zhu, Lingjian,Lei, Ning,Miao, Zhenyuan,Sheng, Chunquan,Zhuang, Chunlin,Yao, Jianzhong,Zhang, Wannian
experimental part, p. 139 - 143 (2012/03/09)
A mild and efficient Knoevenagel-Doebner reaction from malonic acid and a wide range of aldehydes was catalyzed by a catalytic system consisting of β-alanine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affording the corresponding (E)-α,β-unsaturated carboxylic acids in good to excellent yields and with high stereoselectivity. The advantage of the method is that the reaction could proceed smoothly at ambient temperature so that it can tolerate a variety of functional groups and avoid unnecessary side reactions. Copyright
Molecular puzzle ring: Pseudo[1]rotaxane from a flexible cyclodextrin derivative
Miyawaki, Atsuhisa,Kuad, Paul,Takashima, Yoshinori,Yamaguchi, Hiroyasu,Harada, Akira
experimental part, p. 17062 - 17069 (2009/04/13)
A pseudo[1]rotaxane formed by a flexible cyclodextrin (CD) derivative (1-R) with a bulky end group has been investigated on kinetic quantitation. 1-Rs have the cinnamamide moiety as a guest and a bulky end group (R) as a rate-determining moiety of the threading process. The R groups play an important role for the formation of pseudo[1]rotaxane, and kinetics of the self-inclusion process was found to be controlled by the size and shapes of the R groups. 1-Ad and 1-Me derivatives, which have an adamantyl and methyl end group, respectively, formed self-inclusion complexes by threading of the arm moiety with a conformational conversion of altrose from 1C4 form to 4C1 form. Flexibility of the altro-α-CD cavity resulted in an induced fit (from 1C4 to 4C 1) to the arm moiety, and introducing a bulky end group allowed the stability of this pseudo[1]rotaxane to be enhanced.
Conformationally restricted analogs of deoxynegamycin
Raju,Anandan, Sampathkumar,Gu, Shihai,Herradura, Prudencio,O'Dowd, Hardwin,Kim, Bum,Gomez, Marcela,Hackbarth, Corinne,Wu, Charlotte,Wang, Wen,Yuan, Zhengyu,White, Richard,Trias, Joaquim,Patel, Dinesh V.
, p. 3103 - 3107 (2007/10/03)
Deoxynegamycin (1b) is a protein synthesis inhibitor with activity against Gram-negative (GN) bacteria. A series of conformationally restricted analogs were synthesized to probe its bioactive conformation. Indeed, some of the constrained analogs were found to be equal or better than deoxynegamycin in protein synthesis assay (1b, IC50=8.2μM; 44, IC 50=6.6μM; 35e2, IC50=1μM). However, deoxynegamycin had the best in vitro whole cell antibacterial activity (Escherichia coli, MIC=4-16μg/mL; Klebsiella pneumoniae, MIC=8μg/mL) suggesting that other factors such as permeation may also be contributing to the overall whole cell activity. A new finding is that deoxynegamycin is efficacious in an E. coli murine septicemia model (ED50=4.8mg/kg), providing further evidence of the favorable in vivo properties of this class of molecules.
A one-pot synthesis of 3-amino-3-arylpropionic acids
Tan,Weaver
, p. 7449 - 7461 (2007/10/03)
3-Aminopropionic acids (β-amino acids) are biologically active compounds of interest in medicinal and pharmaceutical chemistry. Twenty-one 3-amino-3-arylpropionic acids were synthesized via a facile one-pot synthesis. In addition, a series of mechanistic studies have been performed to optimize the production of these β-amino acids. The reaction mechanism of this one-pot synthesis of β-amino acids, as well as the electronic effect of para-substitution and the influence of solvent polarity on the proposed reaction mechanism are discussed.
A novel class of orally active non-peptide bradykinin B2 receptor antagonists. 2. Overcoming the species difference between guinea pig and man
Abe, Yoshito,Kayakiri, Hiroshi,Satoh, Shigeki,Inoue, Takayuki,Sawada, Yuki,Inamura, Noriaki,Asano, Masayuki,Hatori, Chie,Sawai, Hiroe,Oku, Teruo,Tanaka, Hirokazu
, p. 4053 - 4061 (2007/10/03)
Recently we reported the identification of a series of 8-[[3-(N- acylglycyl-N-methylamino)-2,6-dichlorobenzyl]oxy]-3-halo-2-methytimidazo[1,2- α]pyridines as the first orally active non-peptide bradykinin (BK)B2 receptor antagonists (1-3). Thes
Carboxypeptidase A-Catalyzed Hydrolysis of α-(Acylamino)cinnamoyl Derivatives of L-β-Phenyllactate and L-Phenylalaninate: Evidence for Acyl-Enzyme Intermediates
Suh, Junghun,Cho, Wonhwa,Chung, Shin
, p. 4530 - 4535 (2007/10/02)
The (CPA) carboxypeptidase A-catalyzed hydrolysis of α-(acetylamino)- (1), α-(benzoylamino)- (2), or α-cinnamoyl ester (3) of L-β-phenyllactate manifested small values of both kcat and Kmapp.On the other hand, the corresponding amides of L-Phe showed enhanced kcat and unaffected Kmapp values.At -2 deg C, accumulation of an intermediate was observed spectrophotometrically immediately after mixing of 6x10-5 M CPA with 4x10-5 M 3.This is the most stable (in terms of half-life and Kmapp) intermediate ever reported for the CPA-catalyzed reactions.For 2 and 3, kcat was independent of pH over pH 5.5-9.5.Although attempts to trap the intermediate with external or intramolecular trapping reagents were unseccesful, the very small Kmapp and the pH independence of kcat for 2 and 3 provide evidence that shows that the accumulating intermediate is the anhydride acyl-CPA intermediate.The temperature dependence and the D2O effect were measured for the kcat values of 2 and 3.The different effects of the α-(acylamino)cynnamoyl groups on the kinetic parameters for esters and for peptides were explained in terms of a single mechanism with the intermediacy of an acyl-enzyme.
