ChemInform Abstract: Copper‐Mediated 1,4‐Conjugate Addition of Boronic Acids and Indoles to Vinylidenebisphosphonate Leading to gem‐Bisphosphonates as Potential Antiresorption Bone Drugs.

Organocatalytic Enantioselective Epoxidation of Some Aryl-Substituted Vinylidenebisphosphonate Esters: On the Way to Chiral Anti-Osteoporosis Drugs

“…As a follow-up to our previous work in this area [15,20,21], in this paper we report the epoxidation of a series of monosubstituted prochiral VBPs using different possible oxidants and catalyzed by enantiopure organocatalysts, observing, in some specific cases, interesting levels of stereoselective induction. We also report some subsequent attempts to open the oxirane ring to lead to the formation of enantioenriched BPs having an -OH group between the two P atoms, a feature that improves their affinity with hydroxyapatite [22], i.e., the major mineral constituent of bone.…”

“…This situation reflects the problems of dealing synthetically with molecules having a bisphosphonate group which induces (i) a strong electrophilicity on the central C atom and eventually on adjacent moieties; (ii) a significant steric hindrance leading in many cases to limited accessibility and poor reactivity; and (iii) the capacity of strongly binding metal ions, thereby inactivating catalysts in transition metal-catalyzed reactions. A useful synthetic approach allowing the formation of a broad range of BPs is based on vinylidenebisphosphonate precursors (VBPs) as starting materials [15][16][17][18]. The application of a series of enantioselective catalytic reactions based on the use of a variety of nucleophilic reagents towards these precursors opens the way to the possibility of obtaining a wide range of structurally complex BPs, and in principle the opportunity to verify the different behaviors of the synthesized enantiomers.…”

“…A useful synthetic approach allowing the formation of a broad range of BPs is based on vinylidenebisphosphonate precursors (VBPs) as starting materials [15][16][17][18]. The application of a series of enantioselective catalytic reactions based on the use of a variety of nucleophilic reagents towards these precursors opens the way to the possibility of obtaining a wide range of structurally complex BPs, and in principle the opportunity to verify the different behaviors of the synthesized enantiomers.…”

Synthesis of new indole-based bisphosphonates and evaluation of their chelating ability in PE/CA-PJ15 cells

“…For compound 1f, a basic pK a of 7.96 is also predicted for the azaindole scaffold. According to literature protocols [40], few attempts to obtain the free bisphosphonic acid derivatives have been made to experimentally evaluate the effect of the ester group (e.g. Scheme SI1).…”

Nitrile Containing Bisphosphonates: Easy Synthesis through Metal Catalyzed Michael Addition

“…Conversely, BPs with R 1 = H are directly obtained by Michael addition of nucleophiles to vinylidenebisphosphonate tetraethylester (VBP) as a typical building block leading to several classes of BPs endowed with heteroatoms . Other fruitful reaction of addition to VBP were recently disclosed by our group focusing on boronic acids and indoles addition . The exploration of new strategies to prepare a wide range of highly efficient N‐BPs is a big challenge for the scientific community and several synthetic approaches have been proposed in the past.…”