53581-86-5Relevant academic research and scientific papers
Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α-CH2-Oxygenation of Free Amines
Ghosh, Santanu,Jana, Chandan K.
, p. 260 - 266 (2018/02/19)
Direct oxidation of α-CH2 group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C-H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide.
Chemoselective Reduction of Sterically Demanding N,N-Diisopropylamides to Aldehydes
Xiao, Peihong,Tang, Zhixing,Wang, Kai,Chen, Hua,Guo, Qianyou,Chu, Yang,Gao, Lu,Song, Zhenlei
, p. 1687 - 1700 (2018/02/23)
A sequential one-pot process for chemoselectively reducing sterically demanding N,N-diisopropylamides to aldehydes has been developed. In this reaction, amides are activated with EtOTf to form imidates, which are reduced with LiAlH(OR)3 [R = t-Bu, Et] to give aldehydes by hydrolysis of the resulting hemiaminals. The non-nucleophilic base 2,6-DTBMP remarkably improves reaction efficiency. The combination of EtOTf/2,6-DTBMP and LiAlH(O-t-Bu)3 was found to be optimal for reducing alkyl, alkenyl, alkynyl, and 2-monosubstituted aryl N,N-diisopropylamides. In contrast, EtOTf and LiAlH(OEt)3 in the absence of base were found to be optimal for reducing extremely sterically demanding 2,6-disubstituted N,N-diisopropylbenzamides. The reaction tolerates various reducible functional groups, including aldehyde and ketone. 1H NMR studies confirmed the formation of imidates stable in water. The synthetic usefulness of this methodology was demonstrated with N,N-diisopropylamide-directed ortho-metalation and C-H bond activation.
Total Synthesis of Tambromycin by Combining Chemocatalytic and Biocatalytic C?H Functionalization
Zhang, Xiao,King-Smith, Emma,Renata, Hans
supporting information, p. 5037 - 5041 (2018/03/27)
A combination of genomic and metabolomic approaches recently resulted in the identification of a nonribosomal tetrapeptide tambromycin, which possesses promising antiproliferative activity and several unusual structural features, including a densely substituted indole, a methyloxazoline ring, and an unusual pyrrolidine-containing amino acid called tambroline. In this work, we identify a concise synthetic route to access tambromycin, which relies on the strategic use of biocatalytic and chemocatalytic C?H functionalization methods to prepare two key precursors to the natural product in an efficient and scalable manner. The success of our study highlights the benefits of applying the principles of biocatalytic retrosynthesis as well as C?H functionalization logic to the synthesis of complex molecular scaffolds.
Flow Chemistry on Multigram Scale: Continuous Synthesis of Boronic Acids within 1 s
Hafner, Andreas,Meisenbach, Mark,Sedelmeier, Joerg
supporting information, p. 3630 - 3633 (2016/08/16)
The benefits and limitations of a simple continuous flow setup for handling and performing of organolithium chemistry on the multigram scale is described. The developed metalation platform embodies a valuable complement to existing methodologies, as it combines the benefits of Flash Chemistry (chemical synthesis on a time scale of 1 s) with remarkable throughput (g/min) while mitigating the risk of blockages.
A frank synthesis of alkyl-aryl ethers from 2-halobenzaldehydes and aromatic olefins without transition metal co-catalyst and ligand
Kumar, Balagani Sathish,Negi, Arvind S.
, p. 2340 - 2344 (2015/04/22)
An efficient synthesis of alkyl ethers has been developed for o-deactivated aryl halides and 1-halotetralenes. The method shows good regioselectivity towards ortho substituted halides. Alkali metal carbonates (Li2CO3/Na2CO3/K2CO3/Cs2CO3) have been used without a transition metal co-catalyst and ligand. The method is simple, straight-forward and proceeds to afford products in good isolated yields. The method holds potential for future applications in organic synthesis.
Small molecule inhibitors of anthrax lethal factor toxin
Williams, John D.,Khan, Atiyya R.,Cardinale, Steven C.,Butler, Michelle M.,Bowlin, Terry L.,Peet, Norton P.
, p. 419 - 434 (2014/01/17)
This manuscript describes the preparation of new small molecule inhibitors of Bacillus anthracis lethal factor. Our starting point was the symmetrical, bis-quinolinyl compound 1 (NSC 12155). Optimization of one half of this molecule led to new LF inhibitors that were desymmetrized to afford more drug-like compounds.
Modulation on C- and N-terminal moieties of a series of potent and selective linear tachykinin NK2 receptor antagonists
Gensini, Martina,Altamura, Maria,Dimoulas, Tula,Fedi, Valentina,Giannotti, Danilo,Giuliani, Sandro,Guidi, Antonio,Harmat, Nicholas J. S.,Meini, Stefania,Nannicini, Rossano,Pasqui, Franco,Tramontana, Manuela,Triolo, Antonio,Maggi, Carlo Alberto
experimental part, p. 65 - 78 (2010/11/16)
Herein we describe the synthesis of a series of new potent tachykinin NK2 receptor antagonists by the modulation of the Cand N-terminal moieties of ibodutant (MEN 15596, 1). The Nterminal benzo[b]thiophene ring was replaced by different substituted naphthalenes and benzofurans, while further modifications were evaluated at the C-terminal tetrahydropyran moiety. Most compounds demonstrated a high affinity for the human NK2 receptor and high in vitro antagonist potency, indicating that a wide range of substituents at both termini can be incorporated in the molecule without detrimental effects on the interactions with the NK2 receptor. Selected compounds were tested in vivo confirming their activity as NK2 antagonists. In particular, after both iv and id administration to guinea pig, compound 61b was able to antagonize NK2-induced colonic contractions with a potency and duration-of-action fully comparable to the reference compound 1 (MEN 15596, ibodutant).
Design, synthesis, and SAR of cis-1,2-diaminocyclohexane derivatives as potent factor Xa inhibitors. Part I: Exploration of 5-6 fused rings as alternative S1 moieties
Yoshikawa, Kenji,Yokomizo, Aki,Naito, Hiroyuki,Haginoya, Noriyasu,Kobayashi, Shozo,Yoshino, Toshiharu,Nagata, Tsutomu,Mochizuki, Akiyoshi,Osanai, Ken,Watanabe, Kengo,Kanno, Hideyuki,Ohta, Toshiharu
experimental part, p. 8206 - 8220 (2010/04/06)
A series of cis-1,2-diaminocyclohexane derivatives were synthesized with the aim of optimizing previously disclosed factor Xa (fXa) inhibitors. The exploration of 5-6 fused rings as alternative S1 moieties resulted in two compounds which demonstrated improved solubility and reduced food effect compared to the clinical candidate, compound A. Herein, we describe the synthesis and structure-activity relationship (SAR), together with the physicochemical properties and pharmacokinetic (PK) profiles of some prospective compounds.
6-SUBSTITUTED PHENOXYCHROMAN CARBOXYLIC ACID DERIVATIVES
-
Page/Page column 140, (2010/01/30)
Compounds of Formula (I): in which A1, A2, W, L, G, R7a, R7b, R8, R9 and R10 have the meanings given in the specification, are DP2 receptor modulators useful in the treatment of immunologic diseases.
Synthesis and structure-activity relationships of second-generation hydroxamate botulinum neurotoxin A protease inhibitors
Capkova, Katerina,Yoneda, Yoshiyuki,Dickerson, Tobin J.,Janda, Kim D.
, p. 6463 - 6466 (2008/04/02)
Botulinum neurotoxins are the most toxic proteins currently known. Based on a recently identified potent lead structure, 2,4-dichlorocinnamic acid hydroxamate, herein we report on the structure-activity relationship of a series of hydroxamate BoNT/A inhibitors. Among them, 2-bromo-4-chlorocinnamic acid hydroxamate, 2-methyl-4-chlorocinnamic acid hydroxamate, and 2-trifluoromethyl-4-chlorocinnamic acid hydroxamate displayed comparable inhibitory activity to that of the lead structure.
