Formal total synthesis of the PKC inhibitor, balanol: preparation of the fully protected benzophenone fragment

Synthesis of 7-alkylidene-7,12-dihydroindolo[3,2-d]benzazepine-6-(5H)-ones (7-alkylidene-paullones) by N-cyclization–oxidative Heck cascade and characterization as sirtuin modulators

“…), which also 5 corroborated the geometry of the exocyclic olefin, as anticipated from the stereospecific syn-β-elimination of PdL 2 XH from intermediate III depicted on Figure 2. As a result, it is confirmed that the products of this highly regio-, stereo-and chemoselective reaction indeed correspond to a 7-10 exo intramolecular Heck-type cyclization process, whereas the indolobenzazezinone products (originating from the alternative 8-endo cyclization manifold 28,29 ), which have been observed in other substrates, 30 were not detected. Furthermore, the only products that were isolated originated 15 from the manifold where the N further removed from the pendant alkenyl chain participated in the starting nucleopalladation step.…”

“…4 Cytotoxic, 5 antiproliferative, 6 and pro-apoptotic 1b,7 effects of paullones have been noted in human cancer cell lines, rendering these compounds as promising antitumor agents. 8 Additionally, paullones have been considered as therapeutic agents for 30 trypanosomiasis and leishmaniasis, 9 and selected members of the family (cazpaullone 1c and alsterpaullone 1d) 10 for the treatment of diabetes since they suppress cytokine induced β-cell apoptosis. 11 These promising biological activities have raised the interest in 35 these compounds and have stimulated the development of synthetic methodologies to prepare analogues retaining the basic 7,12-dihydroindolo [3,2-d]benzazepine-6(5H)-one scaffold.…”

Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

“…1 . 2,3-bis(dibenzyloxy)benzonic acid 2 (80%) was generated from commercially available 2,3-bis(hydroxyl)benzonic acid 1 28 . Aminoalcohol 3a–c and 2 were condensed using HOBt/DCC to obtain the desired benzamides ( 4a–c ) with up to 90% yield 29 .…”

The Meyers Reaction (1994-2010)

“…After depro- Balanol (116) is an example of protein kinase C (PKC) inhibitors (Scheme 21). The synthesis of a perbenzylated derivative of balanol's benzophenone fragment (115) was described by Skrydstrup employing a regioselective Heck reaction as the key step for the connection of two aromatic rings [55]. The synthesis started with preparation of the disubstituted benzoic acid 113 by substitution of the 2-benzyloxy group in 112 with vinyl magnesium bromide (111) at 25 °C in 90% yield.…”