Industry: Chemical Region: Germany Transaction price: US$ 1 million Transaction method: equity investment
Project introduction:
In the past, the evaluation of pentafluorocyclopropyl as a chemical form in crop protection and medicinal chemistry has been affected by the lack of suitable methods to actually combine this part with advanced synthetic intermediates. A sulfonium salt, 5- (pentafluorocyclopropyl)-dibenzothiophene trifluoromethanesulfonate, was synthesized and used as a general reagent for photoinduced cyclopropylation of pentafluorocyclopentafluoride, and a wide range of (hetero) aromatic hydrocarbons were realized through free radical-mediated mechanism.
The typical benefits of fluorine substitution in candidate drugs are resistance to oxidative metabolism, lipophilic changes dependent on (poly) fluorination mode, and some degree of conformational control, which is usually counterintuitive. In addition, structurally challenging novel (poly) fluorinated motifs are often incorporated into structures with therapeutic significance. In the past, the evaluation of pentafluoropropyl groups as chemical types in crop protection and medicinal chemistry has been affected by the lack of appropriate methods to actually combine pentafluoropropyl groups into advanced synthetic intermediates. Although cyclopropyl ring is common in the structure of candidate drugs, its pentafluoride counterpart (formally derived from the cyclization of two terminal -CF3 units in HFIP) still does not exist in drug optimization activities.
Scientists at Georg August University in Gö ttingen synthesized a sulfonium salt, 5- (pentafluoropropyl)-dibenzothiophene trifluoromethanesulfonate, and used it as a general reagent for photoinduced cyclopropanation of pentafluorocyclopentafluoride.
In order to realize cyclopropylation of electrophilic fluorine, the basic chemical structure of dibenzothiophene was used in particular. Umemoto reagent is an organic compound developed in 1990s for trifluoromethylation, and pentafluoropropyl is attached to dibenzothiophene instead of trifluoromethyl. New reagents 5- (pentafluoropropyl) dibenzothiophene trifluoromethanesulfonate and 5- (tetrafluoropropyl) dibenzothiophene mesylate were formed as intermediates. Subsequently, pentafluorocyclopropylation is carried out, that is, pentafluorocyclopropene is transferred to (hetero) aromatic hydrocarbons by photo-oxidation reduction catalysis. Under photochemical conditions (e.g., irradiation with a blue diode with a large wavelength of 462nm) and in the presence of an electron donor-acceptor (EDA) complex, pentafluorocyclopropyl radicals are generated, which are used as substituents in medical reagents and bioactive molecules.
advantage
+Late functionalization of drugs and pesticides
The+pentafluoropropane moiety is selectively installed at predictable sites of natural nucleophilic sites of many heterocyclic substrates.
+Simple experimental program
+photoinduced transfer
+Two photocatalytic schemes allow a wide range of pentafluoropropane (hetero) aromatics to be obtained through C-H functionalization.
+Doek scale synthesis
The late functionalization of heterocyclic drugs and pesticides is of great value to the synthesis of fine chemicals and their scientific and medical applications. Because of its ability to polyfluorinate biologically related molecules and widely used drugs in the later stage of functionalization and its easy application, it gives new properties to previously nonfunctional (hetero) aromatic hydrocarbons through free radical-mediated mechanism.
Cooperation mode:
This study has successfully achieved multi-gram synthesis, and established photocatalysis, which has been patented. Looking for technology licensing partners, welcome to contact.