A new and versatile approach to the preparation of valuable deoxynucleoside 3′-phosphite intermediates

Marugg, J. E.; Burik, A.; Tromp, M.; Marel, G.A. van der; Boom, Jacques H. van

doi:10.1016/s0040-4039(00)84506-2

Cited by 64 publications

(27 citation statements)

References 14 publications

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“…The deoxyribonucleoside 3'-H-phosphonates are key intermediates in the synthesis of oligodeoxyribonucleotides by the H-phosphonate approach. However, only a few methods have been reported for the synthesis of H-phosphonate units [3,[14][15][16][17]. One method, reported by Garegg et al [3], involves the use of tris(imidazol-1-yl)phosphine, an unstable reagent that is generated in situ.…”

Section: Resultsmentioning

confidence: 99%

Use of new phosphonylating and coupling agents in the synthesis of oligodeoxyribonucleotides via the H-phosphonate approach

Sakatsume¹,

Yamane²,

Takaku³

et al. 1990

Nucl Acids Res

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New phosphonylating and coupling agents for the synthesis of oligodeoxyribonucleotides via H-phosphonate approach have been developed. Tris(1,1,1,3,3,3-hexafluoro-2-propyl) phosphite, prepared by the reaction of lithium salt of 1,1,1,3,3,3-hexafluoro-2-propoxide with PCl3, reacts with deoxyribonucleosides in the presence of a catalytic amount of triethylamine to produce in the high yield the corresponding deoxyribonucleoside 3'-H-phosphonate units. The use of a new coupling reagent, 1,3-dimethyl-2-chloro-imidazolinium chloride (DMCI) for the internucleotidic H-phosphonate bond formation via the H-phosphonate approach is also discussed in detail.

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Section: Resultsmentioning

confidence: 99%

Use of new phosphonylating and coupling agents in the synthesis of oligodeoxyribonucleotides via the H-phosphonate approach

Sakatsume¹,

Yamane²,

Takaku³

et al. 1990

Nucl Acids Res

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“…Bis(N,N‐diisopropylamino)chlorophosphine . Bis( N,N ‐diisopropylamino)chlorophosphine is relatively inexpensive and has been used to generate nucleoside H ‐phosphonates in high yields (70% to 91%; Marugg et al, ,b; Nahum et al, ). Reaction of bis( N,N ‐diisopropylamino)chlorophosphine with a nucleoside proceeds through a nucleoside phosphite intermediate, which can be converted to the corresponding nucleoside H ‐phosphonate monoester via acidolysis.…”

Section: Commentarymentioning

confidence: 99%

Synthesis of Amino Acid Phosphoramidate Monoesters via H‐Phosphonate Intermediates

Choy

Drontle

Wagner

2006

CP Nucleic Acid Chemistry

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This unit describes a method for generating nucleoside phosphoramidate monoesters (S.3 and S.4; Fig. 15.1.1) from H-phosphonate intermediates (S.2). Two different methods are outlined for generating H-phosphonate monoesters. Both methods are simple and utilize readily available phosphitylating reagents. The nucleoside H-phosphonate monoesters are subsequently oxidized to the nucleoside phosphoramidates in the presence of iodine and the appropriate amino acid methyl ester.Phosphitylation. The Basic Protocol utilizes diphenyl phosphite as the phosphitylating agent. Diphenyl phosphite is inexpensive, is easy to handle, and produces high yields of the H-phosphonate monoester (S.2). This method involves reaction of diphenyl phosphite with a nucleoside followed by a basic work-up to yield the nucleoside H-phosphonate monoester.The Alternate Protocol utilizes bis(N,N-diisopropylamino)chlorophosphine as the phosphitylating agent. Bis(N,N-diisopropylamino)chlorophosphine is more reactive than diphenyl phosphite, is relatively inexpensive and easy to handle, and produces high yields of the H-phosphonate. Nucleosides are reacted with bis(N,N-diisopropylamino)chlorophosphine to generate a nucleoside bis(N,N-diisopropylamino)phosphine intermediate, followed by an acidic work-up to yield the nucleoside H-phosphonate monoesters.

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“…To synthesize Tpc3Um (2), the thymidine 3Ј-phosphorodiamidite derivative 5 was prepared according to the method reported by van Boom et al [16] Compound 5 was condensed with 3Ј-O-acetyl-5-(hydroxypropyl)-2Ј-Omethyluridine (6) [10] in the presence of 1H-tetrazole [17] to give the triester block 7 as a diastereomeric mixture in 85% yield, as shown in Scheme 1. Scheme 1.…”

Section: Synthesis and 1 H Nmr Analysis Of Tpc3um 2a And 2b With S/nmentioning

confidence: 99%

“…In situ acylation of 13 with benzoic anhydride in the presence of DMAP, followed by treatment with 80% acetic acid, gave the 3Ј-O-benzoylated product 14 in 64% overall yield from 11. Cyclization of 14 with bis(diisopropylamino)(2-cyanoethoxy)phosphane, [16] followed by oxidation with tBuOOH, [21] gave the desired product 15, which was converted into 16 in situ, in 64% overall yield from 14 (Scheme 2). …”

Section: Requirement Of the 2ј-hydroxy Group For Stabilization Of Thementioning

confidence: 99%

Essential Factors for Stabilization of the Predominant C3′-endo Conformation in Dinucleoside Phosphotriester Derivatives with Cyclonucleotide Bridge Structures at the Downstream 3′-Position

et al. 2001

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This paper describes the synthesis of conformationally constrained dinucleoside cyclic phosphotriester derivatives and related compounds, such as Tpc3Um (2), Tpc3dU (3), Tpc2dU (4), pc3dU (16), and pc2dU (25), where c2 and c3 refer to ethylene and propylene bridges between the 5Ј-phosphate of the 3Ј-downstream nucleoside and the 5-position of the uracil residue. These studies found that the c3 linker is essential for fixing the 3Ј-downstream nucleoside residue in the [a]

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A new and versatile approach to the preparation of valuable deoxynucleoside 3′-phosphite intermediates

Cited by 64 publications

References 14 publications

Use of new phosphonylating and coupling agents in the synthesis of oligodeoxyribonucleotides via the H-phosphonate approach

Use of new phosphonylating and coupling agents in the synthesis of oligodeoxyribonucleotides via the H-phosphonate approach

Synthesis of Amino Acid Phosphoramidate Monoesters via H‐Phosphonate Intermediates

Essential Factors for Stabilization of the Predominant C3′-endo Conformation in Dinucleoside Phosphotriester Derivatives with Cyclonucleotide Bridge Structures at the Downstream 3′-Position

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