Transient protection: efficient one-flask syntheses of protected deoxynucleosides

Ti, Gavrilova; Gaffney, Barbara L.; Jones, Richard A.

doi:10.1021/ja00369a029

Cited by 453 publications

(253 citation statements)

References 6 publications

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“…Deoxynucleosides were purchased from Vega Biochemicals and protected according to the procedure of Jones (8). Methyldichloro (5) To a mixture of 3.0 g (15.7 mmol) of 2 and 1.53 g (15.7 mmol, 1 eq) of triethylamine in 100 ml of diethylether at -100C under a nitrogen atmosphere was added 1.32 g (15.7 mmol, 1 eq) of morpholine over 15 min.…”

Section: Reagents and Solventsmentioning

confidence: 99%

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

1984

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Deoxynucleoside phosphoramidites can be prepared in good yield from deoxynucleosides, bis-dialkylaminophosphines, and the corresponding dialkylamine hydrotetrazolide or tetrazole as catalysts. These phosphoramidites generated in situ lead to the direct synthesis of deoxyoligonucleotides on polymer supports. INTRODUCTIONThe current phosphite triester methodology for deoxyoligonucleotide synthesis requires the condensation of deoxynucleoside phosphoramidites 7a-d or 8a-d, activated by tetrazole, with the 5'-hydroxyl group of a deoxynucleoside or deoxyoligonucleotide attached covalently to a polymer support (1-4). Although these phosphoramidites can be prepared by existing methods (5,6) from the appropriately protected deoxynucleosides la-d, the chlorophosphines 2 and 3 used in forming 7a-d and 8a-d, respectively, are difficult to prepare and easily react with trace amounts of water. Moreover, the high reactivity of 2 and 3 and the concomitant production of insoluble amine hydrochloride salts preclude their use for any strategy involving the in situ generation of deoxynucleoside phosphoramidites for deoxyoligonucleotide synthesis on solid supports (7). Because of our interest in the latter approach, we were prompted to investigate the relative stability and reactivity of the aminophosphines 4, 5, and 6 towards phosphodiester formation. We wish to report that the phosphoramidites 7a-d and 8a-d can be prepared in good yields by the reaction of suitably protected deoxynucleosides la-d and bis-dialkylaminophosphines 4 or 6 using amine salts 9 and 10, respectively, as catalysts. This method was applied to a

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Section: Reagents and Solventsmentioning

confidence: 99%

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

1984

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“…We envisioned that, upon transient protection [27] of the nitrogen atom, the amount of 1c could be reduced. For this purpose, trimethylsilyl protecting group (TMS) seemed to be a reasonable choice.…”

Section: Resultsmentioning

confidence: 99%

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Sipőcz¹,

Lengyel²,

Sipos³

et al. 2016

J Flow Chem

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A novel method for C-H functionalization of heteroaromatic rings by using continuous-flow reactors is reported. Direct alkylation reactions were investigated under heterogeneous catalytic conditions using simple transition metal catalysts at elevated temperature and pressure. As a model reaction, the alkylation of indole was attempted using cheap Raney W Nickel catalyst. Alcohols served both as alkylating agent and as reaction media. The targeted 3-alkyl-indoles were obtained in moderate to good yield with reasonable selectivity. Transient protection on the N-atom increased the selectivity up to 80%. The scope and limitations were also investigated. In summary, direct alkylation with alcohols represents a rapid (residence time of <1 min) and traceless process with high atom economy (88-92%, in those cases where transient protection was not applied).

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“…Fortunately, the N-glycosylic bond of nucleosides 2a,b is significantly more stable than that of purine nucleoside 1. Thus, phenoxyacetyl as well as benzoyl groups were successfully introduced into compound 2a when 2,4,5-trichlorophenyl phenoxyacetate (21) or benzoyl chloride were used and the transient protection protocol was employed (29) (2a→5a,b). The yield of the bis-phenoxyacylated derivative 5a was rather low (30%) while the bis-benzoylated nucleoside 5b was isolated in 63% yield (Scheme 3).…”

Section: Monomersmentioning

confidence: 99%

Pyrazolo[3,4-d]pyrimidine Nucleic Acids: Adjustment of the dA-dT to the dG-dC Base Pair Stability

Budow

Seela

2003

Nucleosides, Nucleotides and Nucleic Acids

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Transient protection: efficient one-flask syntheses of protected deoxynucleosides

Cited by 453 publications

References 6 publications

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

In situactivation of bis-dialkylaminophosphines—a new method for synthesizing deoxyoligonucleotides on polymer supports

Regioselective Catalytic Alkylation of N-Heterocycles in Continuous Flow

Pyrazolo[3,4-d]pyrimidine Nucleic Acids: Adjustment of the dA-dT to the dG-dC Base Pair Stability

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