Industry: Digital technology 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 was hindered by the lack of suitable methods to actually incorporate it into synthetic intermediates. German experts synthesized a sulfonium salt, 5- (pentafluoropropyl)-dibenzothiophene trifluoromethanesulfonate, and used it as a general reagent for photoinduced pentafluorocyclopropenylation, and realized various (hetero) aromatic hydrocarbons through free radical-mediated mechanism.
Industry challenge
The typical benefits of fluorine substitution in candidate drugs are resistance to oxidative metabolism, lipophilic changes dependent on (poly) fluorination patterns, and a certain degree of conformational control, which is usually counterintuitive. In addition, structurally challenging novel (poly) fluorinated motifs are usually incorporated into structures with therapeutic significance. In the past, the evaluation of pentafluorocyclopropyl as a chemical type in crop protection and medicinal chemistry was hindered by the lack of an appropriate method to actually incorporate it 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) is still missing in drug optimization activities.
Innovative solutions
Scientists from a German university synthesized a sulfonium salt, 5- (pentafluoropropyl)-dibenzothiophene trifluoromethanesulfonate, and used it as a general reagent for light-induced propenylation of pentafluoropyclopropene.
In particular, the basic chemical structure of dibenzothiophene was used to realize electrophilic cyclopropylation of fluorine. For Umemoto reagent, an organic compound developed in 1990s for trifluoromethylation, pentafluoropropyl is linked to dibenzothiophene instead of trifluoromethyl. New reagents 5- (pentafluoropropyl) dibenzothiophene trifluoromethanesulfonate and 5- (tetrafluoropropyl) trifluoromethanesulfonyl thiophene trifluoroethanesulfonate were formed as intermediates. Followed by pentafluorocyclopropylation, that is, the pentafluorocyclopropylation is transferred to (hetero) aromatic hydrocarbons by photoredox catalysis. Under photochemical conditions (for example, irradiated by a blue diode with a large wavelength of 462nm), in the presence of electron donor-acceptor (EDA) complexes, pentafluoropropyl radicals will be generated and become substituents in drugs and bioactive molecules.
superiority
● Late functionalization of drugs and pesticides
Pentafluorocyclopropane moieties are selectively installed at predictable sites in the natural nucleophilic sites of many heterocyclic substrates.
● The operability of the experimental program.
● Light-induced transfer
Two photocatalytic schemes, allowing various pentafluoropropane (hetero) aromatic hydrocarbons to be obtained through C-H functionalization.
Low gram scale synthesis
app; application
The late functionalization of heterocyclic drugs and pesticides is of great value to the synthesis of industrial fine chemicals and their scientific and medical applications. Because it can polyfluorinate biologically related molecules and widely used drugs in the later stage of functionalization, and it is easy to be applied, it gives new properties to previously unfunctionalized (hetero) aromatic hydrocarbons through free radical-mediated mechanism.
Cooperation mode:
This technology provides patent licensing cooperation.