Towards 20,20-difluorinated bryostatin: synthesis and biological evaluation of C17,C27-fragments

Abstract

The syntheses of compounds corresponding to 20,20-difluorinated C17–C27 fragments of bryostatin are reported together with preliminary PKC binding data.

Synthesis of gem-Difluoro-3,4-dihydro-2H-pyrans via a TfOH-Catalyzed [4 + 2] Annulation of Difluoroenoxysilanes with α-Cyano Chalcones

“…3 The gem-difluoro bryosta (Figure 1, II), a complex marine macrolide, has demonstrated potent binding activities with protein kinase C (PKC). 4 The gem-difluoro ripostatin analogue (Figure 1, III) has been certified as an efficient inhibitor of RNA polymerase (RNAP). 5 Additionally, the gemdifluoro thromboxane (Figure 1, IV) possesses powerful contractile effects on vascular tissues and has the ability to initiate platelet aggregation.…”

“…For instance, analogues of phlorizin (Figure , I ), a fluorinated carbohydrate derivative, have shown great potential in the treatment of diabetes and obesity . The gem -difluoro bryosta (Figure , II ), a complex marine macrolide, has demonstrated potent binding activities with protein kinase C (PKC) . The gem -difluoro ripostatin analogue (Figure , III ) has been certified as an efficient inhibitor of RNA polymerase (RNAP) .…”

Defluoroalkylation of sp3 C−F Bonds of Industrially Relevant Hydrofluoroolefins

“…The difluoromethylene group (-CF 2 -) itself is at arget of interest due to its inclusion in an umbero fi sosteresi nmedicinal chemistry. [7][8][9] To give some examples,t he selective alkylation of trifluoromethyl benzened erivatives with ketones or alkenes has been achieved throughr eactions that generate either carbocation or radical intermediates. [10,11] Thel atter species can be produced electrochemically [12] or by carefullyc onstructed photoredox catalytic cycles.…”