Simultaneous Removal of two 2-cyano-1,1-dimethylethyl Groups from Bis(2-cyano-1,1-dimethylethyl) Thymidine 3′-phosphate Derivatives by the Use of DBU/BSA

Sekine, Mitsuo; Tsuruoka, Hiroyuki; Iimura, Soshi; Wada, Takehiko

doi:10.1080/10575639408043933

Cited by 20 publications

(16 citation statements)

References 13 publications

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“…The removal of the O-2-cyanothyl group from 13a-e (X = S) was performed by the BSA/DBU procedure. 26 Analysis of the 31 P NMR spectra of the crude products of reaction showed that their major components had chemical shifts close to those expected for 4a-e. For the crude products 31 P NMR chemical shifts of ca. 101 ppm (CDCl 3 ) were observed, which were similar to those observed for the nucleoside monoester phosphorodithioates (88.6-90.6 ppm, Et 3 NH + salts, D 2 O solution).…”

Section: Lpa Phosphorodithioates (4a-e)mentioning

confidence: 70%

“…58 ppm, characteristic of phosphorothioate O,O-diesters). The O-2-cyanoethyl groups were removed according to the procedure described by Sekine et al 26 by the action of DBU on 13a-e (X = O), after its silylation with N,O-bis(trimethylsilyl)acetamide (BSA). The final 1-acyloxy-2-O-methyl-sn-glycerol-3-O-phosphorothioates 3a-e were isolated as ammonium salts in 40-48% yield, after ion-exchange on a Amberlyst s -NH 4 + resin in 90% aqueous methanol solution.…”

Section: The Synthesis Of Sulfur Analogues Of Lpamentioning

confidence: 99%

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The chemical synthesis of phosphorothioate and phosphorodithioate analogues of lysophosphatidic acid (LPA) and cyclic phosphatidic acid (CPA)

2010

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The chemical synthesis of new sulfur analogues of lysophospholipids has been described, including phosphorothioate/phosphorodithioate derivatives of lysophosphatidic acids (LPA) and phosphorothioate/phosphorodithioate derivatives of cyclic phosphatidic acids (cPA). For the preparation of LPA and cPA derivatives both oxathiaphospholane and dithiaphospholane approaches have been employed. Each lysophospholipid analogue has been synthesized as a series of five compounds, bearing five different fatty acid residues, both saturated (12 : 0, 14 : 0, 16 : 0, 18 : 0) and unsaturated (18 : 1), in the form of ammonium salts. The phosphorodithioate analogues of LPA were obtained as triethylammonium salts, however these were not stable and decomposed when transformed into the ammonium salt by ion exchange in aqueous methanol solution. The new sulfur analogues of LPA and cPA may share interesting biological properties of their parent compounds, and previously synthesized derivatives may behave as regulators of many metabolic processes and hopefully show new biological activity.

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Section: Lpa Phosphorodithioates (4a-e)mentioning

confidence: 70%

Section: The Synthesis Of Sulfur Analogues Of Lpamentioning

confidence: 99%

The chemical synthesis of phosphorothioate and phosphorodithioate analogues of lysophosphatidic acid (LPA) and cyclic phosphatidic acid (CPA)

2010

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“…Phosphorylation proceeded almost quantitatively with either reagent. After oxidation and capping, the phosphate-protecting groups (the cyanoethyl and sulfonylethyl groups) were removed by treatment with 1,8-diazabicyclo[5.4.0]undec-7-ene-bis(trimethylsilyl)acetamide (DBU–BSA) ( 12 , 19 ). Finally, 130-mer monophosphorylated at the 5′-end was converted to the triethylammonium salt by treatment with triethylamine-MeOH and used for the pyrophosphorylation studies described below.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and biological activity of artificial mRNA prepared with novel phosphorylating reagents

Nagata

Hamasaki

Uetake

et al. 2010

Nucleic Acids Research

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Though medicines that target mRNA are under active investigation, there has been little or no effort to develop mRNA itself as a medicine. Here, we report the synthesis of a 130-nt mRNA sequence encoding a 33-amino-acid peptide that includes the sequence of glucagon-like peptide-1, a peptide that stimulates glucose-dependent insulin secretion from the pancreas. The synthesis method used, which had previously been developed in our laboratory, was based on the use of 2-cyanoethoxymethyl as the 2′-hydroxy protecting group. We also developed novel, highly reactive phosphotriester pyrophosphorylating reagents to pyrophosphorylate the 5′-end of the 130-mer RNA in preparation for capping. We completed the synthesis of the artificial mRNA by the enzymatic addition of a 5′-cap and a 3′-poly(A) tail to the pyrophosphorylated 130-mer and showed that the resulting mRNA supported protein synthesis in a cell-free system and in whole cells. As far as we know, this is the first time that mRNA has been prepared from a chemically synthesized RNA sequence. As well as providing a research tool for the intracellular expression of peptides, the technology described here may be used for the production of mRNA for medical applications.

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“…The use of the non-nucleophilic activator CMPT and oxidizer CSO was necessary for the efficient production of 4; replacement of CMPT with nucleophilic 1H-tetrazole resulted in a significant decrease in the yield (from 84% to 35%), while the use of t-BuOOH, assuming it is more nucleophilic than CSO, resulted in complete decomposition of 2 and quantitative recovery of 1. It should be noted that the remaining 2-cyanoethyl group of 4 could not be removed by treatment with DBU in the presence of N,O-bis(trimethylsilyl)acetamide, 18 and compound 4 was gradually decomposed to the starting material 1, 19 indicating that a different protecting group that can be removed under milder conditions should be used for the synthesis of inosine 6-phosphate monoester derivatives.…”

mentioning

confidence: 99%

“…CMMT also accelerated the reaction of 1 with 5a; the reaction time was shortened to 15 min (entry 2). Finally, phosphoramidite 5b completely suppressed the debenzylation because of the 2-cyano-1,1-dimethylethyl group, 18,21 which is a more labile protecting group than 2-cyanoethyl. The desired inosine 6-(benzyl phosphate) derivative 6a was isolated in 87% yield (entry 3).…”

mentioning

confidence: 99%

Synthesis of inosine 6-phosphate diesters via phosphitylation of the carbonyl oxygen

et al. 2013

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Simultaneous Removal of two 2-cyano-1,1-dimethylethyl Groups from Bis(2-cyano-1,1-dimethylethyl) Thymidine 3′-phosphate Derivatives by the Use of DBU/BSA

Cited by 20 publications

References 13 publications

The chemical synthesis of phosphorothioate and phosphorodithioate analogues of lysophosphatidic acid (LPA) and cyclic phosphatidic acid (CPA)

The chemical synthesis of phosphorothioate and phosphorodithioate analogues of lysophosphatidic acid (LPA) and cyclic phosphatidic acid (CPA)

Synthesis and biological activity of artificial mRNA prepared with novel phosphorylating reagents

Synthesis of inosine 6-phosphate diesters via phosphitylation of the carbonyl oxygen

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