Bisphosphonates chemistry

Bisphosphonates that have been approved for clinical use, as reported in the Annual Report of Medicinal Chemistry, are listed in Tab. 15.1. It should be noted that although a BP may have gained initial approval for a specific clinical indication, its subsequent use in various countries may not be necessarily limited to that indication. 

Horner-Wadsworth-Emmons procedures are also commonplace in synthetic materials chemistry, recent examples including donor-acceptor substituted molecules with bicyclo-spacers, which require napthalene-, anthracene-, and pyrene-substituted phosphonates, (112), (113) and (114) respectively, well-defined, electroactive PPE/PPV copolymers through the condensation of dialdehydes and bisphosphonate (115), ° and triphenylamine-substituted PPV. ° ... 

The interest in all these themes really is not decreasing, indeed some fascinating areas of research are emerging or are the subject of many investigations the medicinal chemistry of bisphosphonates, the role of phosphorus in biology, phosphorus ligands in radiopharmaceutical chemistry, phosphorus in material science, new polymers and dendrimers incorporating phosphorus, and asymmetric catalysis to name but a few. 

In continuation of studies on the formation and reactions of 1-hydroxyalkyl-l,1-bisphosphonic acid cyclic esters (Organophosphoms Chemistry, 1988, j, 161), the a,u-dioxoalkanediphosphonic tetraesters (167 n=3-8) have been shown to react with more hydrogen phosphonate to give the a, (u-dihydroxy-a, o, u), co-bis [ bis phosphonic acid)] esters (168) cross-reactions e.g., between (167b) and dimethyl phosphonate (affording the same product as that obtained from (167a)... 

Ebetino FH, Hogan AL, Sun S, Tsoumpra MK, Duan X, Triffitt JT, Kwaasi AA, Dunford JE, Barnett BL, Oppermann U et al (2011) The relationship between the chemistry and biological activity of the bisphosphonates. Bone 49 20-33... 

Thin films of a-ZrRPs are grown at a variety of surfaces with relative ease due to the dependable chemistry of Zr(IV) phosphonate linkage chemistry and the availability of a variety of phosphonic and bisphosphonic acids. Several examples are discussed later to illustrate these features. Functionalization of silica surfaces, for example, via treatment with an organosilane bearing a phosphonic acid or by treatment with ZrOCli can be used for the construction of a-ZrRP layers on silica substrates (230). The thin films are grown layer by layer with controlled molecular thickness (see Fig. 15). This ability to control both thickness and chemical nature of the films provides unprecedented control over the construction of multilayer molecular films. 

Turhanen has reported a synthesis of novel (co-allqmyl-l-hydrojgr-l, -diyl)bisphosphonic acid tetramethyl esters (398), their dimethyl esters (399), and trimethyl ester derivatives (400), as useful substrates in click chemistry. Thus, the reaction of bisphosphonate dimethyl ester (399) (n = 2) and tri methyl ester (400) (n = 2) with azide functionalised triethylene glycol (401) afforded triethylene glycol-bisphosphonate conjugates (402) and (403), respectively (Scheme 122). ... 

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