Facile installation of the phosphonate and (α,α-difluoromethyl)phosphonate functionalities equipped with benzyl protection

Berkowitz, David B.; Bhuniya, Debnath; Peris, Gorka

doi:10.1016/s0040-4039(99)00077-5

Cited by 37 publications

(20 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9,62,63 Work to date towards glycosyl a-halophosphonate analogs has focused on the introduction of a-uoro and a,a-diuorophosphonates at various positions of O-and C-glycosides (e.g. 11,[65][66][67] These examples illustrate the accessibility of a-uorophosphonates; however, until recently there was no corresponding precedent to the abrominated phosphonates on a carbohydrate scaffold. 12,64 Important advances in the synthesis of both a-uorinated and a,a-diuorinated glucosyl-6-phosphonates have been described by the Berkowitz group (Scheme 11).…”

Section: A-bromophosphonates On a Carbohydrate Scaffoldmentioning

confidence: 99%

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

Downey

Cairo

2014

Med. Chem. Commun.

View full text Add to dashboard Cite

Substrate phosphorylation is a key modulator of signal transduction. Abnormal phosphorylation in vivo is implicated in many diseases including cancer, diabetes, and Alzheimer's disease. Inhibitors of phosphaterecognizing proteins have potential as medicinal agents as well as tools to study phosphorylation pathways. A well-known and common inhibition strategy is to synthetically replace the labile phosphate moiety with a non-hydrolyzable phosphonate. Fully saturated, a-fluoro and a,a-difluorophosphonates are often effective phosphate bioisosteres and have been well studied. More recently a-brominated phosphonates have begun to emerge as inhibitors of phosphate recognizing enzymes, some of which operate by irreversible mechanisms. Herein we discuss the synthetic approaches to aliphatic and benzylic a-bromophosphonates and their biological activities.Scheme 5 The synthesis of an aliphatic a-bromophosphonate derivative. 52 Scheme 6 An improved synthetic strategy to alkyl abromophosphonates. 53This journal is

show abstract

Section: A-bromophosphonates On a Carbohydrate Scaffoldmentioning

confidence: 99%

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

Downey

Cairo

2014

Med. Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…It is worthy of note that we have developed complementary fluorinated phosphonate reagents, carrying both dibenzyl (Berkowitz et al, 1999) and diallyl (Berkowitz and Sloss, 1995) phosphonate protection. Both reagents have performed well in model triflate displacement studies, and may, in the future, allow for adaptation of these routes to the synthesis of pCF 2 -Ser monomers bearing more convenient side chain protecting groups.…”

Section: Introductionmentioning

confidence: 99%

The α,α-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction

Panigrahi

Eggen

Maeng

et al. 2009

Chemistry & Biology

Self Cite

View full text Add to dashboard Cite

SUMMARY This overview focuses on the (α,α-difluoromethylene)phosphonate mimic of phosphoserine (pCF2Ser) and its application to the study of kinase-mediated signal transduction – pathways of great interest to drug development. The most versatile modes of access to these chemical biological tools are discussed, organized by method of PCF2-C bond. The pCF2-Ser mimic may be site-specifically incorporated into peptides (SPPS) and proteins (expressed protein ligation). This isopolar, dianionic pSer mimic results in a “constitutive phosphorylation” phenotype, and is seen to support native protein-protein interactions that depend upon serine phosphorylation. Signal transduction pathways studied with this chemical biological approach include the regulation of p53 tumor suppressor protein activity, and of melatonin production. Given these successes, the future is bright for the use of such “teflon phospho-amino acid mimics” to map kinase-based signaling pathways.

show abstract

“…To synthesise polyfunctionalised molecules bearing α-fluoro-β-ketophosphonate moieties, dibenzyl protection on the phosphoryl group appeared to be the only alternative, since this can easily and quickly be cleaved by reduction under mild and neutral conditions, even in the presence of fluorine atoms on the C α ϪP. [22] However, the general route through condensation of the dibenzyl α,α-difluoromethanephosphonate carbanion with carboxylic esters or carboxylic acid chlorides would no longer be applicable, since this carbanion is too unstable to react. [23] Reaction with a triflate group is the only previously reported successful example, by Berkowitz.…”

Section: Introductionmentioning

confidence: 99%

“…[23] Reaction with a triflate group is the only previously reported successful example, by Berkowitz. [22] Consequently, no dibenzyl α-fluoromethyl-β-ketophosphonate has previously been isolated.…”

Section: Introductionmentioning

confidence: 99%

A Convenient Synthesis of Dibenzyl α,α-Difluoromethyl-β-ketophosphonates

2002

View full text Add to dashboard Cite

Facile installation of the phosphonate and (α,α-difluoromethyl)phosphonate functionalities equipped with benzyl protection

Cited by 37 publications

References 50 publications

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

Synthesis of α-brominated phosphonates and their application as phosphate bioisosteres

The α,α-Difluorinated Phosphonate L-pSer-Analogue: An Accessible Chemical Tool for Studying Kinase- Dependent Signal Transduction

A Convenient Synthesis of Dibenzyl α,α-Difluoromethyl-β-ketophosphonates

Contact Info

Product

Resources

About