197893-07-5Relevant academic research and scientific papers
Amidation of carboxylic acids via the mixed carbonic carboxylic anhydrides and its application to synthesis of antidepressant (1S,2R)-tranylcypromine
Ezawa, Tetsuya,Kawashima, Yuya,Noguchi, Takuya,Jung, Seunghee,Imai, Nobuyuki
, p. 1690 - 1699 (2017/11/14)
Primary amidations of carboxylic acids 1 or 3 with NH4Cl in the presence of ClCO2Et and Et3N were developed to afford the corresponding primary amides in 22% to quantitative yields. Additionally, we have applied the amidation to the preparation of various amides containing hydroxamic acids and achieved the synthesis of (1S,2R)-tranylcypromine as an antidepressant medicine via Lossen rearrangement.
2-(N-Benzyl-N-phenylsulfonamido)alkyl amide derivatives as γ-secretase inhibitors
Parker, Michael F.,Barten, Donna M.,Bergstrom, Carl P.,Bronson, Joanne J.,Corsa, Jason A.,Dee, Michael F.,Gai, Yonghua,Guss, Valerie L.,Higgins, Mendi A.,Keavy, Daniel J.,Loo, Alice,Mate, Robert A.,Marcin, Larry R.,McElhone, Katharine E.,Polson, Craig T.,Roberts, Susan B.,MacOr, John E.
, p. 6828 - 6831,4 (2020/09/02)
A series of (N-benzyl-N-phenylsulfonamido)alkyl amides were developed from classic and parallel synthesis strategies. Compounds with good in vitro and in vivo γ-secretase activity were identified and described.
Carbamates of 4′-demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects
Chen, Shi-Wu,Gao, Yuan-Yu,Zhou, Ni-Ni,Liu, Jie,Huang, Wen-Ting,Hui, Ling,Jin, Yan,Jin, Yong-Xin
supporting information; experimental part, p. 7355 - 7358 (2012/02/04)
In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4′-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4′-demethyl- 4-deoxypodophyllic)-α-amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4′- demethyl-4-deoxypodophyllic)-d-α-methine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.
A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams), a new class of serine protease inhibitors, using acyliminium methodology
Macdonald, Simon J. F.,Clarke, Geoffrey D. E.,Dowle, Michael D.,Harrison, Lee A.,Hodgson, Simon T.,Inglis, Graham G. A.,Johnson, Martin R.,Shah, Prit,Upton, Richard J.,Walls, Steven B.
, p. 5166 - 5175 (2007/10/03)
A flexible, practical, and stereoselective synthesis of enantiomerically pure trans-5-oxohexahydropyrrolo[3,2-b]pyrroles (pyrrolidine-trans-lactams) is described. The key reaction involves addition of Z-ketene acetal 24 to the acyliminium ion derived from 48. This reaction is mediated by BF3. OEt2 and introduces the 6S and 6aS stereocenters stereoselectively. The acyliminium precursor was prepared in four different ways: from racemic 2,4- diaminobutyric acid 8, from (R)-asparagine, from (R)-methionine, and via a crystallization-induced dynamic resolution of a salt of the racemic amine 56. (R)-Methionine is the preferred starting material for the preparation of enantiomerically pure material. The best conditions for addition of the ketene acetal to the acyliminium ion derived from 48 were determined by systematically screening a range of ketene acetals and Lewis acids. The best ketene acetal was Z-(1-ethoxy-3-methylbut-1-enyloxyl)triisopropylsilane 24. In this series, the bulk of the silyl group of the Z-ketene acetal can be correlated with increased 6S isopropyl product. Use of the E-ketene acetal does not lead to a significant change in stereoselectivity for the 6R isopropyl product. In contrast, variation of the Lewis acid has a considerable effect on the product stereochemistry. While BF3·OEt2 gives predominantly 6S,6aS product, AlCl3 and TiCl4 give predominantly mixtures of the 6R,6aS and 6S,6aS products and TMSOTf gives 6aR material with predominantly one unknown isopropy] isomer (trans-lactam numberings used). The synthesis can conveniently be carried out on a large scale to produce multigram quantities of the trans-lactam 28, which is a key precursor of pharmacologically active molecules such as 1, a selective and orally active human neutrophil elastase inhibitor. The overall chemical yield of 1 is 1.3%, corresponding to an average of >70% yield for each of the 14 steps, and the synthesis contains only one chromatographic purification.
