Preparation of L-(Phosphonodifluoromethyl)phenylalanine derivatives as non-hydrolyzable mimetics of O-phosphotyrosine

Wrobel, Jay; Dietrich, Arlene

doi:10.1016/s0040-4039(00)73631-8

Cited by 63 publications

(21 citation statements)

References 23 publications

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“…It is based on the use of trimethylsilyl trifluoromethanesulfonate (TMS-OTf) as silylating agent, trifluoroacetic acid (TFA) as acidic reagent, and dimethylsulfide (DMS) and m -cresol to avoid side reactions (from S N 1 or S N 2 mechanism) [ 204 ] that can involve the functional groups present in the amino acid or peptide. These conditions were applied to prepare the compound 82 from 81 [ 205 – 206 ] ( Fig. 24 ).…”

Section: Reviewmentioning

confidence: 99%

Phosphonic acid: preparation and applications

Sevrain¹,

Berchel²,

Couthon³

et al. 2017

Beilstein J. Org. Chem.

147

103

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The phosphonic acid functional group, which is characterized by a phosphorus atom bonded to three oxygen atoms (two hydroxy groups and one P=O double bond) and one carbon atom, is employed for many applications due to its structural analogy with the phosphate moiety or to its coordination or supramolecular properties. Phosphonic acids were used for their bioactive properties (drug, pro-drug), for bone targeting, for the design of supramolecular or hybrid materials, for the functionalization of surfaces, for analytical purposes, for medical imaging or as phosphoantigen. These applications are covering a large panel of research fields including chemistry, biology and physics thus making the synthesis of phosphonic acids a determinant question for numerous research projects. This review gives, first, an overview of the different fields of application of phosphonic acids that are illustrated with studies mainly selected over the last 20 years. Further, this review reports the different methods that can be used for the synthesis of phosphonic acids from dialkyl or diaryl phosphonate, from dichlorophosphine or dichlorophosphine oxide, from phosphonodiamide, or by oxidation of phosphinic acid. Direct methods that make use of phosphorous acid (H3PO3) and that produce a phosphonic acid functional group simultaneously to the formation of the P–C bond, are also surveyed. Among all these methods, the dealkylation of dialkyl phosphonates under either acidic conditions (HCl) or using the McKenna procedure (a two-step reaction that makes use of bromotrimethylsilane followed by methanolysis) constitute the best methods to prepare phosphonic acids.

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Section: Reviewmentioning

confidence: 99%

Phosphonic acid: preparation and applications

Sevrain¹,

Berchel²,

Couthon³

et al. 2017

Beilstein J. Org. Chem.

147

103

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“…Synthetic approaches toward CF 2 ‐substituted phosphoamino acid mimetics by us and others have provided 4‐phosphonodifluoromethyl phenylalanine (F 2 Pmp 6 )1–5 and 2‐amino‐4,4‐difluoro‐4‐phosphonobutanoic acid (F 2 Pab 7 )6, 7 as nonhydrolyzable pTyr and pSer mimetics, respectively. Alternatively, synthesis of 2‐amino‐4,4‐difluoro‐3‐methyl‐4‐phosphonobutanoic acid (F 2 Pmab 8 ) as a CF 2 ‐substituted pThr mimetic initially was lacking due to paucity of efficient methodologies for construction of the secondary CF 2 phosphonate unit.…”

Section: Synthesis Of Nonhydrolyzable Phosphoamino Acidsmentioning

confidence: 99%

“…Bioisosteres corresponding to naturally occurring peptides or amino acids have recently received much attention due to their potential utility in medicinal and biological chemistry. Among the mimetics for amino acids or peptides, nonhydrolyzable phosphoamino acids1–8 and ( E )‐alkene dipeptide isosteres (EADIs)9–23 have become synthetic targets because of increasing demand for their mimetics in the development of peptide‐lead drugs. In this article, we briefly review our synthetic studies on phosphatase‐resistant phosphoamino acids corresponding to phosphothreonine (pThr) and its incorporation into a peptide with development of deprotecting methodologies suitable for phosphopeptides 8.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of fluorine‐containing bioisosteres corresponding to phosphoamino acids and dipeptide units

Otaka¹,

Mitsuyama²,

Watanabe³

et al. 2004

Biopolymers

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It has been shown that fluorinated analogues of naturally occurring biological active compounds including amino acids often exhibit unique physiological activity. Among wide varieties of fluorine-containing amino acids, nonhydrolyzable phosphoamino acids possessing a substituent of the difluoromethylene (CF(2)) unit for the phosphoryl ester oxygen are of value in the medicinal and biological fields. We have engaged in the synthesis of these classes of nonhydrolyzable phosphoamino acids corresponding to pTyr 3, pSer 4, and pThr 5 with their incorporation into peptides using newly developed deprotecting procedures. In this article, stereoselective synthesis of the CF(2)-substituted pThr mimetics and development of a two-step deprotecting methodology for the nonhydrolyzable analogues are reviewed. In the course of the above synthetic study, we found that gamma,gamma-difluoro-alpha,beta-enoates were reduced to gamma-fluoro-beta,gamma-enoates by organocopper reagents and then applied to the synthesis of (Z)-fluoroalkene dipeptide isosteres, which have served as potential dipeptide mimetics having structural as well as electrostatic similarity to the parent peptide bonds. Furthermore, mechanistic investigation of the organocopper-mediated reduction led us to development of a SmI(2)-mediated approach toward the synthesis of the fluoroalkene isosteres.

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“…[21] The resulting N-Boc-4-carboxyphenylalanine methyl ester 11 was N-deprotected with TFA and reprotected employing Fmocsuccinimide (FmocOSu) to furnish 12, which was activated as carboxylic acid chloride and used in a Michaelis-Arbuzov acylation of tribenzyl phosphite to provide the 4-(O,O'-dibenzyl-phosphonocarbonyl) derivative 13 of N-Fmoc-phenylalanine methyl ester. [22] As the dibenzylphosphonate 13 was cleaved rapidly by piperidine [23] under the conditions used for Fmoc removal, nucleophilic monodebenzylation of 13 was accomplished with lithium bromide, yielding the monobenzyl phosphonate 14.…”

mentioning

confidence: 99%