Synthesis of 1-hydroxy-1,1-bisphosphonates

Lecouvey, Marc; Leroux, Yves

doi:10.1002/1098-1071(2000)11:7<556::aid-hc15>3.0.co;2-n

Cited by 42 publications

(21 citation statements)

References 33 publications

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“…They are standardly prepared by a large-scale, one-step reaction of carboxylic acids with phosphorus trichloride and phosphorous or phosphoric acids, followed by hydrolysis with water; the procedure was optimized by Kieczykowski et al [14]. The reaction is carried out in selected solvents (phenylsulphonic acid, various phenols, chlorobenzene, diphenyl ether or ionic liquids) with sulfone and methanesulphonic acid being preferred choices [11,[15][16][17][18][19][20]. Despite many theories [19,[21][22][23], the exact mechanism of this reaction is not fully understood; however, the formation of acid chloride as a first intermediate has been undoubtedly demonstrated (Scheme 1).…”

Section: Synthesis From Carboxylic Acidsmentioning

confidence: 99%

“…The reaction is carried out in selected solvents (phenylsulphonic acid, various phenols, chlorobenzene, diphenyl ether or ionic liquids) with sulfone and methanesulphonic acid being preferred choices [11,[15][16][17][18][19][20]. Despite many theories [19,[21][22][23], the exact mechanism of this reaction is not fully understood; however, the formation of acid chloride as a first intermediate has been undoubtedly demonstrated (Scheme 1). This intermediate may react with methanesulphonic acid (when used as a solvent), and the formed mixed anhydride is also considered a potential intermediate for the next step [24], which is an Arbuzov-like reaction of phosphorus acid or one of its several derivatives (including anhydrides of variable structure [17]) formed during the reaction.…”

Section: Synthesis From Carboxylic Acidsmentioning

confidence: 99%

“…Presumably, the addition of phosphites to ketophosphonates was the first procedure for preparation of dialkyl 1-hydroxy-1,1-bisphosphonates [16,19,57]. Starting ketophosphonates are obtained by the Arbuzov reaction of acyl chlorides with trialkyl phosphites and used as substrates in the next step, namely, the addition of dialkyl phosphite to carbonyl double bonds (a representative example for preparation of tetramethyl pamidronate 22 is shown in Scheme 13).…”

Section: Synthesis Via Ketophosphonatesmentioning

confidence: 99%

“…A useful modification of this procedure is the application of tris(trimethylsilyl) phosphite, followed by the easy removal of ester groups by methanolysis [23,60,61]. This was used to prepare a wide variety of 1-hydroxy-1,1-bisphosphonates containing amino groups [19,23,[61][62][63]. Additionally, the use of bis((trimethylsilyl)oxy)phosphine generated from ammonium hypophosphite was applied to prepare hydroxybisphosphinic acids (also presented in Scheme 13) [64].…”

Section: Synthesis Via Ketophosphonatesmentioning

confidence: 99%

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Synthetic Procedures Leading towards Aminobisphosphonates

Chmielewska

Kafarski

2016

Molecules

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Abstract:Growing interest in the biological activity of aminobisphosphonates has stimulated the development of methods for their synthesis. Although several general procedures were previously elaborated to reach this goal, aminobisphosphonate chemistry is still developing quite substantially. Thus, innovative modifications of the existing commonly used reactions, as well as development of new procedures, are presented in this review, concentrating on recent achievements. Additionally, selected examples of aminobisphosphonate derivatization illustrate their usefulness for obtaining new diagnostic and therapeutic agents.

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Section: Synthesis From Carboxylic Acidsmentioning

confidence: 99%

Section: Synthesis From Carboxylic Acidsmentioning

confidence: 99%

Section: Synthesis Via Ketophosphonatesmentioning

confidence: 99%

Section: Synthesis Via Ketophosphonatesmentioning

confidence: 99%

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Synthetic Procedures Leading towards Aminobisphosphonates

Chmielewska

Kafarski

2016

Molecules

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“…ALN was synthesized in the lab [15]. LY294002 was purchased from Sigma (Saint-Quentin Fallavier, France).…”

Section: Reagents and Antisense Oligonucleotidesmentioning

confidence: 99%

Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells

Mongerard-Coulanges

Migianu-Griffoni

Lecouvey

et al. 2009

Biochemical Pharmacology

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Bisphosphonates, and more specially nitrogen -containing bisphosphonates, which are in current use for the treatment of bone diseases, demonstrate proapoptotic, antiproliferative, antiangiogenic and anti-invasive properties on tumor cells. The amino -bisphosphonate alendronate is considered as a potential anticancer drug. In the case of A431 cells, which express high levels of VEGF, it had a two-step effect. At 24h, the antitumor properties of alendronate were counterbalanced by a survival process, which consisted of an enhancement of VEGF expression (mRNA and protein secretion) and TGFα secretion. It was only at 48h that alendronate displayed the expected antiproliferative and antiangiogenic properties. The first step, in which the PI3K pathway was engaged, could be prevented by the use of a VEGFantisense oligonucleotide. The combination of such an antisense with small concentrations of alendronate (~2 µM), which is of the order of clinically used concentrations, was shown to have an antiangiogenic effect as soon as 12h.

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The Synthesis of D‐Trihydroxyllysine‐Based Oligopeptides as a Hydrophilic Scaffold and its Application to the Synthesis of Bifunctional Chelating Agents for Use as Bone Tracers

Tanaka

Ando

Abe

et al. 2008

Chemistry An Asian Journal

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An effective hydrophilic scaffold composed of D-trihydroxyllysine-based oligopeptides and its application in the synthesis of the various (111)In-DTPA conjugates with mono- to penta-bisphosphonate units for use as bone tracers are described. The D-trihydroxyllysine derivative with three orthogonal protecting groups was conjugated with functional devices at the gamma position and allowed oligomerization based on peptide chemistry. The radiopharmaceutical complexes of (111)In(III) with selected chelators, 4 and 8, were suitable for bone imaging. These results show that D-trihydroxyllysine 2 was an effective building block for the synthesis of multivalent ligands applicable to medical use.

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Synthesis of 1-hydroxy-1,1-bisphosphonates

Cited by 42 publications

References 33 publications

Synthetic Procedures Leading towards Aminobisphosphonates

Synthetic Procedures Leading towards Aminobisphosphonates

Impact of alendronate and VEGF-antisense combined treatment on highly VEGF-expressing A431 cells

The Synthesis of D‐Trihydroxyllysine‐Based Oligopeptides as a Hydrophilic Scaffold and its Application to the Synthesis of Bifunctional Chelating Agents for Use as Bone Tracers

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