1143-50-6Relevant articles and documents
Visible-Light-Induced Cycloaddition of α-Ketoacylsilanes with Imines: Facile Access to β-Lactams
Ye, Jian-Heng,Bellotti, Peter,Paulisch, Tiffany O.,Daniliuc, Constantin G.,Glorius, Frank
supporting information, p. 13671 - 13676 (2021/05/11)
We report the synthesis of β-lactams from α-ketoacylsilanes and imines, which proceeds via a formal [2+2] photochemical cycloaddition with in situ generation of siloxyketene. This mild and operationally simple reaction proceeds in an atom-economic fashion with broad substrate scope, including aldimines, ketimines, hydrazones, and fused nitrogen heterocycles, affording a variety of important β-lactams with satisfactory diastereoselectivities in most cases. This reaction also features good functional-group tolerance, facile scalability and product diversification. Experimental and computational studies suggest that α-ketoacylsilanes can serve as photochemical precursors by engaging in a 1,3 silicon shift to the distal carbonyl group.
Mechanistic study of a complementary reaction system that easily affords quinazoline and perimidine derivatives
Wang, Zerong Daniel,Eilander, Joshua,Yoshida, Motoko,Wang, Tianzhi
supporting information, p. 7664 - 7674 (2015/04/22)
A new reaction between 2-aminobenzophenone and thiourea in dimethyl sulfoxide (DMSO) has been developed that primarily affords 4-phenylquinazoline as a single product. This reaction is also applicable, in general, to the reactions between thiourea and conformation-restricted β-amino ketones, such as 1-aminoanthracene-9,10-dione and 1-amino-9H-fluoren-9-one, to prepare perimidine derivatives. Experimental data is consistent with our computational study on the thermal decomposition of thiourea to form hydrogen sulfide and carbodiimide. This reaction involves a coupling between 2-aminobenzophenone and carbodiimide generated in situ from thiourea to form 4-phenylquinazolin-2(1H)-imine intermediate, and the generation of sulfur-containing reducing agent from hydrogen sulfide and DMSO, which reduces 4-phenylquinazolin-2(1H)-imine to 4-phenyl-1,2-dihydroquinazolin-2-amine. Elimination of ammonia from the latter yields 4-phenylquinazoline.
Application of the guanidine-acylguanidine bioisosteric approach to argininamide-type NPY Y2 receptor antagonists
Pluym, Nikola,Brennauer, Albert,Keller, Max,Ziemek, Ralf,Pop, Nathalie,Bernhardt, Guenther,Buschauer, Armin
scheme or table, p. 1727 - 1738 (2012/01/14)
Strongly basic groups such as guanidine moieties are crucial structural elements, but they compromise the drug-likeness of numerous biologically active compounds, including ligands of G-protein-coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide-type neuropeptideY (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG-acylated argininamides were obtained by guanidinylation with tailor-made mono-Boc-protected N-acyl-S-methylisothioureas. The compounds were investigated for Y2R antagonism (calcium assays), Y2R affinity, and NPY receptor subtype selectivity (flow cytometric binding assays). Most of the NG-substituted (S)-argininamides showed Y2R antagonistic activities and binding affinities similar to those of the parent compound, whereas NG-acylated or -carbamoylated analogues with a terminal amine were superior (Y2R: Ki and KB values in the low nanomolar range). This demonstrates that the basicity of the compounds, although 4-5 orders of magnitude lower than that of guanidines, is sufficient to form key interactions with acidic amino acids of the Y2R. The acylguanidines bind with high affinity and selectivity to Y2R over the Y1, Y4, and Y5 receptors. As derivatization of the amino group is tolerated, these compounds can be considered building blocks for the preparation of versatile fluorescent and radiolabeled pharmacological tools for invitro studies of the Y2R. The results support the concept of bioisosteric guanidine-acylguanidine exchange as a broadly applicable approach to retain pharmacological activity despite decreased basicity.
