5621-02-3Relevant articles and documents
Site-Selective C–H Functionalization of (Hetero)Arenes via Transient, Non-symmetric Iodanes
Fosu, Stacy C.,Hambira, Chido M.,Chen, Andrew D.,Fuchs, James R.,Nagib, David A.
supporting information, p. 417 - 428 (2019/02/14)
Fosu, Hambira, and colleagues describe the direct C–H functionalization of medicinally relevant arenes or heteroarenes. This strategy is enabled by transient generation of reactive, non-symmetric iodanes from anions and PhI(OAc)2. The site-selective incorporation of Cl, Br, OMs, OTs, and OTf to complex molecules, including within medicines and natural products, can be conducted by the operationally simple procedure included herein. A computational model for predicting site selectivity is also included. The discovery of new medicines is a time- and labor-intensive process that frequently requires over a decade to complete. A major bottleneck is the synthesis of drug candidates, wherein each complex molecule must be prepared individually via a multi-step synthesis, frequently requiring a week of effort per molecule for thousands of candidates. As an alternate strategy, direct, post-synthetic functionalization of a lead candidate could enable this diversification in a single operation. In this article, we describe a new method for direct manipulation of drug-like molecules by incorporation of motifs with either known pharmaceutical value (halides) or that permit subsequent conversion (pseudo-halides) to medicinally relevant analogs. This user-friendly strategy is enabled by combining commercial iodine reagents with salts and acids. We expect this simple method for selective, post-synthetic incorporation of molecular diversity will streamline the discovery of new medicines. A strategy for C–H functionalization of arenes and heteroarenes has been developed to allow site-selective incorporation of various anions, including Cl, Br, OMs, OTs, and OTf. This approach is enabled by in situ generation of reactive, non-symmetric iodanes by combining anions and bench-stable PhI(OAc)2. The utility of this mechanism is demonstrated via para-selective chlorination of medicinally relevant arenes, as well as site-selective C–H chlorination of heteroarenes. Spectroscopic, computational, and competition experiments describe the unique nature, reactivity, and selectivity of these transient, unsymmetrical iodanes.
Antibacterial activity and mechanism of action of the benzazole acrylonitrile-based compounds: In?vitro, spectroscopic, and docking studies
AlNeyadi, Shaikha S.,Salem, Alaa A.,Ghattas, Mohammad A.,Atatreh, Noor,Abdou, Ibrahim M.
, p. 270 - 282 (2017/05/15)
A new series of pyrimidine derivatives 5, 9a-d and 12a-d was synthesized by an efficient procedure. The antibacterial activity of the new compounds was studied against four bacterial strains. Compound 5 was found to exhibit the highest potency, with?=?1.0?μg/ml, against both Escherichia coli and Pseudomonas aeruginosa when compared with amoxicillin (MIC?=?1.0–1.5?μg/mL). Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that compounds 5, 9a-d and 12a-d have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site and were able to overcome amoxicillin resistance in bacteria by inhibiting the β-lactamase enzyme. Docking studies showed that compounds 5, 9a-d and 12a-d inhibit the β-lactamase enzyme through covalent bonding with Ser70. The synergistic effect with amoxicillin was studied. The newly synthesized compounds reported in this study warrant further consideration as prospective antimicrobial agents.
Amidine dications: Isolation and [Fe]-hydrogenase-related hydrogenation
Corr, Michael J.,Gibson, Kirsty F.,Kennedy, Alan R.,Murphy, John A.
supporting information; experimental part, p. 9174 - 9175 (2009/12/05)
(Chemical Equation Presented) This commmunication demonstrates the preparation, isolation, and full characterization of superelectrophilic salts based on amidine dications in organic solvent, as their triflate salts. These dications are highly activated toward regiospecific reaction with hydrogen gas under mild conditions in the presence of a metal catalyst (Pd/C), mimicking the behavior of the natural substrate, N5,N10- methenyltetrahydromethanopterin, in the iron-sulfur cluster-free [Fe]-hydrogenase.
