Copper‐mediated 1,4‐Conjugate Addition of Boronic Acids and Indoles to Vinylidenebisphosphonate leading to gem‐Bisphosphonates as Potential Antiresorption Bone Drugs

Abstract

Scheme 1. Chemical structures of bisphosphonates, pyrophosphoric acid, alendronic acid, zoledronic acid, and VBP.

Chemical approaches to inhibitors of isoprenoid biosynthesis: targeting farnesyl and geranylgeranyl pyrophosphate synthases

“…The Cu-catalyzed 1,4-conjugate addition of boronic acids and indoles to 68 afforded 1,1-bisphosphonates lacking the gem-OH group (Scheme 18). 107 Whereas the reactions with boronic acids proceeded smoothly in toluene, the addition of indoles can be carried out in polar solvents like 1,2-dichloroethane or water with sodium dodecyl sulfate under micellar conditions.…”

Pyrrolidine‐Containing Bisphosphonates as Potential Anti‐Resorption Bone Drugs

“…Through this method, BPs with heterocycles, steroid conjugates, or other functional groups at the β position, such as thiols, have been reported in the literature. General classes of BPs have also been prepared by metal‐catalyzed addition of boronic acids and indoles to VBP, as recently disclosed by our group . Nitrogen‐substituted BPs can be obtained with a multitude of functional groups.…”

“…Through this method, BPs with heterocycles, [14] steroidc onjugates, [15] or other functional groups at the b position, such as thiols, [16] have been reported in the literature. [17,18] groups.F or example, VBP acts as an efficient dienophile [19] for cycloaddition reactions with dienes [20] and nitrones [21] to provide cyclic BPs and isoxazolidine-substituted BPs, respectively. [17,18] groups.F or example, VBP acts as an efficient dienophile [19] for cycloaddition reactions with dienes [20] and nitrones [21] to provide cyclic BPs and isoxazolidine-substituted BPs, respectively.…”

“…General classes of BPs have also been prepared by metal-catalyzed addition of boronic acids and indoles to VBP,asrecently disclosed by our group. [17,18] groups.F or example, VBP acts as an efficient dienophile [19] for cycloaddition reactions with dienes [20] and nitrones [21] to provide cyclic BPs and isoxazolidine-substituted BPs, respectively. BPs with two alkyl derivatives in positions R 1 and R 2 ,o ro ne alkyl and one alkoxyd erivative, could be obtained throught he formation of an ew CÀPb ond by starting from monophosphonates.…”

Stereoselective Synthesis of Chiral Isatin Containing Bisphosphonates as Potential Anti‐Resorption Bone Drugs

“…The latter approach enabled the preparation of several classes of BPs bearing steroid conjugates, heterocycles or thiols . General classes of BPs have been prepared also by metal catalyzed addition of boronic acids and indoles to VBP as recently disclosed by our group . VBP can be efficiently exploited as dienophile for cycloaddition reactions reacting with dienes and nitrones …”