10.1021/jm300648b
The research focuses on the synthesis and evaluation of novel α-fluorinated derivatives based on the ABP688 structural framework, aiming to develop an optimal fluorine-18-labeled positron emission tomography (PET) radiotracer for imaging metabotropic glutamate receptor subtype 5 (mGluR5). The purpose of this research is to create a radiotracer with a longer physical half-life than the existing carbon-11 labeled tracer, [11C]-ABP688, which is limited by the short half-life of carbon-11. The researchers synthesized a series of five α-fluorinated derivatives using a two-step enolization/NFSI α-fluorination method. The most promising candidate, (Z)-16, exhibited a binding affinity (Ki) of 5.7 nM and a clogP value of 2.3. The synthesis involved various chemicals, including ethoxy enone, ethynylmagnesium bromide, SelectFluor, chlorotrimethylsilane, N-fluorobenzenesulfonimide (NFSI), and O-ethylhydroxylamine hydrochloride, among others. The research concluded that (Z)-16 is a potential mGluR5 PET radiotracer, but due to stereochemical preferences, the E-isomer of α-hydroxy derivative (E)-20 was selected for further synthesis, leading to the preparation of (E)-[18F]-16 as a model compound. This compound showed stability in vitro in plasma and PBS and specificity to mGluR5, encouraging the researchers to explore alternative routes to access the Z-isomer selectively.
10.1021/acs.orglett.1c01607
This research presents an enantioselective oxidative cyclization method for synthesizing highly enantioenriched oxazolines and oxazines from N-allyl carboxamides using a chiral triazole-substituted iodoarene catalyst. The study's purpose was to develop a practical approach for constructing chiral 5-membered N-heterocycles, including those with quaternary stereocenters, which are valuable as synthetic building blocks and core structural motifs in biologically active compounds. The method was found to be efficient, with yields up to 94% and enantioselectivities up to 98% ee. Key chemicals used in the process include N-allyl benzamide as the substrate, chiral iodoarene catalysts, acetonitrile as the solvent, Selectfluor as a co-oxidant, and trifluoroacetic acid (TFA) as an acid additive.
10.1002/chem.200801279
The research focuses on the stereoselective synthesis of ADP-2-fluoroheptose, a fluorinated analogue of ADP-l-glycero-b-d-manno-heptopyranose, which serves as an inhibitor of lipopolysaccharide (LPS) biosynthesis in Gram-negative bacteria. The purpose of this study is to develop novel antibacterial agents by targeting the LPS biosynthesis pathway, which is crucial for bacterial cell viability and virulence. The study concludes that the synthesized ADP-2F-heptose is a potent inhibitor of the heptosyl transferase WaaC, with an IC50 of 30 μM, and provides a foundation for the rational design of a new generation of inhibitors for the LPS biosynthetic pathway. The chemicals used in this process include selectfluor, nucleoside diphosphates (NDP), heptosylglycals, and various protecting groups such as pivaloyl and tert-butyldimethylsilyl groups, among others.
10.1002/anie.200802164
The research presents a new strategy for the fluorination of arylboronic acids using palladium complexes, aiming to facilitate the synthesis of currently inaccessible PET tracers. The key chemicals involved in this study include arylboronic acids, which serve as the starting materials and are pre-functionalized at the desired fluorination position. Palladium acetate complex 1, derived from a bidentate ligand containing a neutral and an anionic nitrogen donor atom, plays a crucial role in forming aryl palladium complexes through transmetallation with various arylboronic acids. The electrophilic fluorination reagent selectfluor is used to react with these aryl palladium complexes, resulting in the formation of fluoroarenes. The reaction tolerates a wide range of functional groups and provides a regiospecific, late-stage fluorination method for complex, functionalized molecules. This advancement could significantly impact biomedical research by enabling the synthesis of PET tracers for applications in cancer, neurodegenerative diseases, gene therapy, and drug development.
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