Late‐Stage Fluorination: Fancy Novelty or Useful Tool?

Abstract

Charming fluorine: This Essay examines the recent surge in late-stage fluorination reactions and outlines challenges that need to be overcome to increase the impact of modern fluorination methods on the synthesis of complex organofluorine compounds. It is outlined how an improved understanding of the bonding interactions of fluoride could lead to a new class of mild fluorinating reagents and a range of functional-group-tolerant reactions.

Photooxygenation of an amino-thienopyridone yields a more potent PTP4A3 inhibitor

“…Interestingly, 13 proved to be almost 10-fold more potent than 1 as well as much more stable in solution. While photoxygenation is currently still significantly less popular than the late-stage fluorination of bioactive scaffolds, 29 we suggest that this strikingly straightforward “reagent-free” method to modify the structure and properties of heterocyclic building blocks has great value for expanding the scope of SAR investigations. Our synthesis enables access to a low-nanomolar small molecule inhibitor that should prove to be a valuable tool for a further exploration of PTP4A3’s role in tumor progression.…”

Opportunity Knocks: Organic Chemistry for Fragment‐Based Drug Discovery (FBDD)

“…[10] Compared to the synthesis of larger and more complex compounds,fragments may at first appear to be relatively less challenging.H owever,i no ur experience the design and synthesis of fragments has been more demanding than we had originally anticipated. With hindsight, reasons for this include: * X-ray informed fragment-design often requires chemists to devise tailored synthetic transformations to the central core of the fragment; * Lack of methodology that allows synthetically accessible vectors to incorporate substituents without disrupting the binding interactions; (Table 1) and we have often found polar fragments of this type difficult to make and isolate; * Requirement to retain physicochemical properties commensurate with drug-likeness.…”

Facile room temperature synthesis of fluorine-18 labeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester without azeotropic drying of fluorine-18

“…The most useful route to obtain 18 F-labeled compounds of high specific activity is through nucleophilic fluorination by no-carrier-added [ 18 F]fluoride. [10-19] The first step of the nucleophilic fluorination is to pass the fluorine-18 containing target water through an anion exchange resin to trap the activity as [ 18 F]fluoride. The activity can be eluted as [ 18 F]-salt from the anion exchange resin with a base solution.…”