Efficient catalyst turnover in the phosphitylation of alcohols with phosphoramidites

Brady, Patrick B.; Morris, Elizabeth M.; Fenton, Owen S.; Sculimbrene, Bianca R.

doi:10.1016/j.tetlet.2008.12.065

Cited by 22 publications

(13 citation statements)

References 39 publications

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“…To date, only two reports (25,26) describe catalytic activation of phosphoramidites with efficient turnover of the catalytic species. It is generally accepted that catalyst deprotonation by the product dialkylamine is the main source of catalyst inactivation.…”

Section: Resultsmentioning

confidence: 99%

Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: Enantioselective synthesis of d - myo -inositol-6-phosphate

Jordan

Kayser-Bricker

Miller

2010

Proc. Natl. Acad. Sci. U.S.A.

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Despite the ubiquitous use of phosphoramidite chemistry in the synthesis of biophosphates, catalytic asymmetric phosphoramidite transfer remains largely unexplored for phosphate ester synthesis. We have discovered that a tetrazole-functionalized peptide, in the presence of 10-Å molecular sieves, functions as an enantioselective catalyst for phosphite transfer. This chemistry in turn has been used as the key step in a streamlined synthesis of myo-inositol-6-phosphate. Mechanistic insights implicate phosphate as a directing group for a highly selective kinetic resolution of a protected inositol monophosphate. This work represents a distinct and efficient method for the selective catalytic phosphorylation of natural products.kinetic resolution | organocatalysis T he inositol phosphates and their phosphoinositide relatives are hubs for an extraordinary amount of biochemistry, and there appears to be no wane in the pace of discovery in this field (1-3). Many early efforts have focused on the biochemistry of the inositol lipids, whereas the last decade has seen a revival of interest in the myriad of inositol phosphates and polyphosphates not associated with the lipid bilayer (1). Total syntheses of these compounds and their analogs have played a critical role in enabling high-precision studies of their biochemistry (4). Historically, the strategy for synthesis in this area has been dominated by protecting group manipulations and classical resolution (5). Our laboratory endeavored to take a step forward in 2001, introducing a class of catalysts that rely on catalytic enantioselective transfer of P(V) reagents ( Fig. 1A) (6, 7). This work enabled access to a wide variety of myo-inositol phosphates (8), phosphatidyl-myo-inositol phosphates (9-11), and related analogs, as well as facilitating studies of their biochemistry (12-15).Although catalytic enantioselective P(V) chemistry continues to prove useful, we have observed limitations. First, the nearly exclusive requirement of phenyl substituents on the chlorophosphate P(V) reagent necessitates additional protecting group manipulations in many syntheses (8-11) due to reagent stability and the incompatibility of phenyl phosphate hydrolysis conditions with synthetic schemes. Despite their utility in concert with peptide-based catalysts, chlorophosphates are generally regarded as less reactive and less versatile reagents compared to their phosphorous(III) analogues. In fact, these realities were an impetus for the development of P(III) reagents for complex phosphate and polynucleotide synthesis (16). Second, from the standpoint of asymmetric, catalytic syntheses of phosphoinositides, the P(V) methodology has thus far failed to effectively differentiate the respective 4-or 6-positions of myo-inositol (Fig. 1B) (17), even though it is highly selective for differentiation of the enantiotopic 1-and 3-positions of the myo-inositol ring.We speculate that this discrepancy in 4∕6 vs 1∕3 desymmetrization is due to local structure of the reacting hydroxyl groups (Fig. 2). Whereas the...

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Section: Resultsmentioning

confidence: 99%

Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: Enantioselective synthesis of d - myo -inositol-6-phosphate

Jordan

Kayser-Bricker

Miller

2010

Proc. Natl. Acad. Sci. U.S.A.

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“…These conditions, however, proved to be incompatible with low‐molecular‐weight substrate 11 (Table 1), and sluggish for the phosphitylation of 2′‐acetyl‐Ery A. Furthermore, phosphoramidite 10 a , in the absence of molecular sieves, was highly prone to hydrolysis, and decomposed in the presence of an alternative amine scavenger, phenyl isocyanate 21…”

Section: Methodsmentioning

confidence: 99%

An Approach to the Site‐Selective Deoxygenation of Hydroxy Groups Based on Catalytic Phosphoramidite Transfer

Jordan

Miller

2012

Angewandte Chemie

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Selektiv: Die Desoxygenierung einfacher und komplexer Naturstoffe gelingt mithilfe eines präparativ leicht zugänglichen Phosphoramidits und von Tetrazolkatalysatoren in einem zweistufigen Prozess, ohne die Vorstufen für die Desoxygenierung zu isolieren. Außerdem steuert ein peptidbasierter Tetrazolkatalysator die selektive Desoxyerythromycin‐Synthese (siehe Schema) und überwindet so die Probleme mit ungeschütztem Erythromycin A.

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“…Scheme 5 Hayakawa's general strategy for oligonucleotide synthesis via tetrazole-based catalysis [44] Scheme 6 Sculimbrene's phosphorylation of alcohols via tetrazole-based catalysis [46] The proposed catalytic cycle proceeds via asymmetric nucleophilic P(V) phosphate transfer, achieved through the use of the π-methylhistidine (Pmh) residue, mimicking the action of histidine kinases [39] in the formation of a chiral high energy phospho-imidazolium ion 8 (Scheme 2).…”

Section: Current Phosphoproteomic Toolsmentioning

confidence: 99%

Alternative synthetic tools to phospho-specific antibodies for phosphoproteome analysis: progress and prospects

2013

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Signal transduction cascades in living systems are often controlled via post-translational phosphorylation and dephosphorylation of proteins. These processes are catalyzed in vivo by kinase and phosphatase enzymes, which consequently play an important role in many disease states, including cancer and immune system disorders. Current techniques for studying the phosphoproteome (isotopic labeling, chromatographic techniques, and phosphospecific antibodies), although undoubtedly very powerful, have yet to provide a generic tool for phosphoproteomic analysis despite the widespread utility such a technique would have. The use of small molecule organic catalysts that can promote selective phosphate esterification could provide a useful alternative to current state-of-the-art techniques for use in, e.g., the labeling and pull-down of phosphorylated proteins. This report reviews current techniques used for phosphoproteomic analysis and the recent use of small molecule peptide-based catalysts in phosphorylation reactions, indicating possible future applications for this type of catalyst as synthetic alternatives to phosphospecific antibodies for phosphoproteome analysis.

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Efficient catalyst turnover in the phosphitylation of alcohols with phosphoramidites

Cited by 22 publications

References 39 publications

Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: Enantioselective synthesis of d - myo -inositol-6-phosphate

Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: Enantioselective synthesis of d - myo -inositol-6-phosphate

An Approach to the Site‐Selective Deoxygenation of Hydroxy Groups Based on Catalytic Phosphoramidite Transfer

Alternative synthetic tools to phospho-specific antibodies for phosphoproteome analysis: progress and prospects

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