Bisphosphonate conjugates

Guervenou, J., and Sturtz. G.. Synthesis of. gem-bisphosphonic conjugates of cortisone derivatives. Phosphorus, Sulfur Silicon Relat. Elem., 88, 1, 1994. 

Bisphosphonate conjugates, with potential as chemotherapy agents and potential carriers of cytotoxic radionuclides[160], are synthesized according to the following reaction scheme ... 

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). ... 

Young and co-workers have described the synthesis of radiolabelled bisphosphonates conjugates (486), (487) and (488). All compounds have... 

The reaction afforded the tandem cyclization product 170 as a mixture of two separable isomers together with an a,p-unsaturated cyclic bisphosphonate, which is formed by a direct deprotonation of the vinylic a-proton of 168 and subsequent intramolecular Michael cyclization. The authors described the formation of 170 by the conjugated addition of 168 to 2.2 equivalents of PhLi and subsequent intramolecular Michael reaction in the intermediate 169. It is likely that coordination of the lithium atom to the oxygens of the phosphonates favors formation of the /raw.v-isomer. As shown in Scheme 52, the reactions with bulky naphthyllithiums gave only the fraws-170 isomer. This novel methodology can provide a rapid entry into a variety of cyclic bisphosphonates in good stereoselectivity. 

In 2008, Jorgensen and coworkers reported the first example of the asymmetric conjugate addition of (5-ketoesters 184 to the vinyl bisphosphonate esters 183 catalyzed by the parent cinchona alkaloids (20 mol%) such as dihydroquinine and dihydroqui-nidine [57]. High yields and enantioselectivities (up to 99% ee) were achieved for a wide range of indanone-based (3-ketoesters as well as various 5-tert-butyloxycarbonyl... 

There is a large therapeutic interest in bisphosphonate derivatives, which are stable analogues of the metabolite of pyrophosphate. The bisphosphonate derivative alendonate (172) has been conjugated to either termini of ODNs. Such conjugates may be of use for the delivery of bisphosphonate to target a variety of bone disorders. 

The tailored synthesis of bisphosphonate/hydrazide dually-functionalized conjugate (366) having cross-linkable functionalities that could be used as... 

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