Use of 5-deoxy-ribo-hexofuranose derivatives for the preparation of 5'-nucleotide phosphonates and homoribonucleosides

Mikhailov, S. N.; Padyukova, N. Sh.; Karpeiskii, M. Ya.; Kolobushkina, L. I.; Beigelman, Leon N.

doi:10.1135/cccc19891055

Cited by 16 publications

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“…We next turned our attention to deesterification of the phosphonate moiety. Hydrolysis of nucleoside phosphonate esters has always been problematic, 1a,,4b and with this in mind, we explored several established procedures. When the diethyl esters 17 and 19 were reacted with a 1 N ethanolic sodium hydroxide solution, followed by acidification with Dowex-50 resin (H + ) and workup, the monoethyl phosphonate esters 23 and 24 , respectively, were isolated in reasonable yields (Scheme ).…”

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confidence: 99%

“…Although some of our phosphonic acids are hygroscopic and were difficult to analyze, C 18 reverse phase chromatography followed by lyophilization did allow us to obtain correct elemental analyses without resorting to salt forms. It is worth mentioning that if phosphonic acids are not desired, literature methods are available to convert them to their respective ammonium, ,4a pyridinium, or sodium salts. ,4b …”

Section: Resultsmentioning

confidence: 99%

“…The concept of using phosphonate isosteres to mimic phosphates is not new and has been employed extensively in nucleoside chemistry . Most of the synthetic pathways in the nucleoside area use either Arbuzov , or Wittig , chemistry to attach the 5‘- C- phosphonomethylene group to a 5‘-functionalized nucleoside. More recently an alternative preparative route has been reported in which a suitably protected 5‘- C- phosphonomethylene sugar /unit is used in the glycosylation reaction with an appropriately functionalized nitrogen heterocycle (nucleobase).…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Phosphonate Isosteres of 2‘-Deoxy-1‘,2‘-seco-nucleotides

et al. 1996

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Practical and convergent syntheses of 2‘-deoxy-1‘,2‘-seco-nucleophosphonates and 1‘,2‘-seco-nucleophosphonates are described. Phosphonate chirons derived from d-isoascorbic acid were used in alkylation of functionalized nucleobases to provide the title phosphonate isosteres in good yields. Subsequent deprotection and deesterification led to the 5‘-C-methylenephosphonic acids which were conveniently purified using gravity flow C18 reverse phase column chromatography.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Synthesis of Phosphonate Isosteres of 2‘-Deoxy-1‘,2‘-seco-nucleotides

et al. 1996

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“…Several publications have already addressed the synthesis of 5'-methylenephosphonate-modified nucleotides, dinucleotides, and oligomers [15] [16]. An intriguing strategy for synthesizing 5'-methylenephosphonate-linked oligonucleotides was proposed by Stawinski and co-workers [17].…”

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Hutter

Blaettler

Benner

2002

HCA

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b ) Departement Chemie, ETH Hˆnggerberg, CH-8093 Z¸rich Chimeric DNA molecules containing four different linking groups, the natural phosphate, 5'-methylenephosphonate, bis(methylene)phosphinate, and bis(methylene) sulfone (see Fig. 1), were directly compared for their ability to form duplexes with complementary DNA and DNA chimeras. From melting temperatures for analogous complementary sequences, general conclusions about the impact of geometric distortion of the internucleotide linkage around the two PÀOÀC bridges were drawn, as were conclusions about the impact on duplex stability that arises from the removal of the negative charge in the linking group. Each structural perturbation diminished the melting temperature, by ca. À 2.58 per modification for the 5'-methylenephosphonate, À 3.58 per modification for the bis(methylene)phosphinate, and À 4.58 per modification for the bis(methylene) sulfone linker. These results have implications for DNA chemistry including the design of −antisense× candidates and the proposal of alternative genetic materials in the search for non-terrean life.Upon expanding the size of the oligosulfones beyond the dinucleoside level, however, major differences in the physicochemical behavior compared with natural DNA emerged. Particularly remarkable was the oligosulfone r(ASO 2 USO 2 GSO 2 GSO 2 U-SO 2 CSO 2 ASO 2 U) [5] (SO 2 corresponds to CH 2 SO 2 CH 2 instead of OP(O)(O À )O). The molecule displayed an extraordinary thermal denaturation curve, melting at ca. 808. Upon melting, a large hyperchromicity was observed (> 200%; 25% is typical for the melting of a DNA duplex). The sequence was not, in the Watson-Crick sense, selfcomplementary. Thus, it was concluded that this oligosulfone folded to a rather stable conformation, indeed one of the most stable single-stranded −RNA× structures known. Richert et al. have subsequently examined the conformation of sulfone-linked oligonucleotide analogs, establishing details of the folding [5].The results of these and other experiments suggested that each oligosulfone has its own unique properties and reactivity. Different oligosulfones differing (in some cases) by only one nucleobase displayed different levels of solubility, aggregation behavior, folding, chemical reactivity, and Watson-Crick base-pairing ability. Their properties were often influenced dramatically by adding a single charge to one end of the molecule [6].These results suggested that removing all the phosphate groups of an oligonucleotide introduces such a big change in the molecule×s physicochemical behavior that the effect cannot easily be interpreted. We, therefore, set out to synthesize chimeric sequences were the phosphate groups were replaced one at a time. We hoped to gain a more quantitative understanding of the influence of charge neutralization on duplex stability and conformation, which then would enable us by extrapolation to better understand the unexpected properties of the oligosulfones.The results with these chimeras were again surprising. The incorporation of one ...

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Synthesis Of Nucleosides

Vorbrüggen¹,

1999

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This chapter deals with the synthesis of nucleosides (e.g., the formation of N ‐glycosides of sugars such as D ‐ribose or 2‐deoxy‐D‐ribose with heterocyclic nitrogen bases). The methods of nucleoside synthesis have been treated in a number of reviews and monographs. It is now generally accepted that nucleosides were among the first organic compounds formed at the start of evolution in the early history of our planet earth. To support this point, guanine and adenine were heated with D ‐ribose in seawater, which contains the Lewis acid magnesium chloride as catalyst. One thus obtained the nucleosides guanosine and adenosine together with comparable yields of unnatural α‐nucleosides. The latter were gradually photoanomerized to the thermodynamically more stable compounds in overall yields of 5–6%. The furanose form of ribose reacts faster than the pyranose form. Corresponding syntheses of the pyrimidine nucleosides uridine and cytidine from uracil , cytosine and ribose are more problematic and remain an enigma. The recent conversion of glycolaldehyde‐ O ‐phosphate and formaldehyde to ribose‐2,4‐di‐ O ‐phosphate might give new insights into the prebiotic syntheses of uridine and cytidine. The evidence and hypotheses for these prebiotic conversions and the evolution of RNA, as well as the implications of an “RNA World,” have been reviewed. These RNA nucleosides are reduced in vivo as 5′‐ O ‐diphosphates by ribonucleotide reductases to the corresponding 2′‐deoxynucleosides—the building blocks of DNA such as 2′‐deoxyguanosine. The thermodynamically controlled synthesis of these four building blocks of RNA has implications for the design of efficient, high yielding, new methods for the synthesis of the naturally occurring nucleosides, nucleoside antibiotics, and modified nucleosides that may serve as antimetabolites to fight viral and parasitic diseases and cancer. The nucleoside rings in this chapter are depicted arbitrarily in the anti conformation, as occurs predominantly in the crystal and solution (based primarily on NOE‐ 1 H‐ and 13 C‐NMR measurements) forms of pyrimidine nucleosides. Only a few nucleosides, such as 6‐methyluridine, occur with the heterocyclic ring predominantly in the syn conformation. The synthesis of C ‐nucleosides has been reviewed previously and is not covered in this review.

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Use of 5-deoxy-ribo-hexofuranose derivatives for the preparation of 5'-nucleotide phosphonates and homoribonucleosides

Cited by 16 publications

References 0 publications

Synthesis of Phosphonate Isosteres of 2‘-Deoxy-1‘,2‘-seco-nucleotides

Synthesis of Phosphonate Isosteres of 2‘-Deoxy-1‘,2‘-seco-nucleotides

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Synthesis Of Nucleosides

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