Structural properties of modified deoxyadenosine structures in solution. Impact of the <i>gauche</i> and anomeric effects on the furanose conformation

Koole, Léo H.; Buck, HM Henk; Nyilas, Ágnes; Chattopadhyaya, J.

doi:10.1139/v87-346

Cited by 42 publications

(6 citation statements)

References 24 publications

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“…The sugar−base torsion angle (χ) is −94.8° in the anti range. These values in the solid state differ from those based on solution 1 H NMR data 1 X-ray crystal structure of 3a . …”

Section: Resultscontrasting

confidence: 77%

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹

et al. 2007

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A variant of the semipinacol rearrangement that was observed in our laboratory has been applied to the synthesis of several furanose and pyranose derivatives. The process consists of an "orchestrated" [1,2]-hydride shift with departure of a leaving group from the opposite face. Transient formation of a C=O group is followed by rapid transfer of a hydride-equivalent from the same face from which the leaving group departed, which results in double inversion of stereochemistry at the two vicinal carbon atoms. Treatment of 2'-O- and 3'-O-tosyladenosine with lithium triethylborohydride in DMSO/THF gave the respective 2'- and 3'-deoxynucleoside analogues with beta-D-threo configurations. Identical treatment of 5'-O-TPS-2'-O-tosyladenosine gave 9-(5-O-TPS-2-deoxy-beta-D-threo-pentofuranosyl)adenine. The same [1,2]-hydride shift and stereochemistry with the 5'-OH and 5'-O-TPS compounds demonstrated the absence of remote hydroxyl-group participation. Application of this process to other nucleoside 2'-O-tosyl derivatives gave the 2'-deoxy-threo compounds in good yields. The reaction-rate order was OTs approximately Br >> Cl for 2'-O-tosyladenosine, 2'-bromo-2'-deoxyadenosine, and 2'-chloro-2'-deoxyadenosine (all with beta-d-ribo configurations). Analogous results were obtained with mannopyranoside derivatives with either 4,6-O-benzylidene protection or a free OH group at C4. Deuterium labeling clearly defined the stereochemical course as a cis-vicinal [1,2]-hydride shift on the face opposite to the original cis OH and OTs groups followed by hydride transfer from the face opposite to the [1,2]-hydride shift. Synthetic and mechanistic considerations are discussed.

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“…The sugar−base torsion angle (χ) is −94.8° in the anti range. These values in the solid state differ from those based on solution 1 H NMR data 1 X-ray crystal structure of 3a . …”

Section: Resultscontrasting

confidence: 77%

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹

et al. 2007

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“…All compounds used (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) were prepared in our laboratory and details are published elsewhere. 39-42 7-Cyano-7-deaza-2Јdeoxyguanosine was prepared very recently by cyanilation of protected 14 and subsequent deprotection.…”

Section: Methodsmentioning

confidence: 99%

“…In an extensive and detailed study Chattopadhyaya and coworkers were able to differentiate for the first time between the gauche and anomeric effects by comparison of the thermodynamics of the pseudorotational equilibrium of the pentofuranose moiety in various regular and modified N-and Cnucleosides. [3][4][5][6][7][8][9][10][11][12][13][14] In this manuscript we investigate this phenomenon on 7deazapurine nucleosides. In particular, the tuning of the sugar puckering and also indirectly the conformation about the C(4Ј)᎐C(5Ј) bond of corresponding 2Ј-deoxynucleosides is studied and the influence of various substituents on the steric and stereoelectronic (anomeric) effects is investigated.…”

Section: Introductionmentioning

confidence: 99%

Stereoelectronic effects of modified purine bases on the sugar conformation of nucleosides: pyrrolo[2,3-d]pyrimidines

Rosemeyer¹,

Seela²

1997

J. Chem. Soc., Perkin Trans. 2

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Steric and stereoelectronic effects of 7-and 8-substituents of 7-deaza-2Ј-deoxy-adenosine and -guanosine on the dynamic sugar puckering as well as on the conformation about the C(4Ј)᎐C(5Ј) bond have been studied. (i) The higher the electron-attracting effect of the substituents, the more the N S (North South) equilibrium of the pentofuranose moiety is biased towards the N-conformation. (ii) The higher the electron-withdrawing effect of the 7-substituents, the higher the (ϩ)g (ϩsc) rotamer population around the C(4Ј)᎐C(5Ј) bond. The interdependencies of the conformational equilibria of 7-deazapurine nucleosides and their influence on oligonucleotide secondary structures are discussed.

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“…Koole et al, 1987) because the 04' lone pair orientation in nucleosides is most optimal in 04'-exo (W-type) conformations, which are virtually inaccessible for steric reasons, as discussed above. However, as we will show subsequently, this effect may help stabilize conformations in the southwestern quadrant such as the rr conformation observed for some anti-HIV nucleosides.…”

Section: H>=mentioning

confidence: 99%

A Stereochemical Rationale for the Activity of Anti-HIV Nucleosides

Taylor

Roey

Schinazi

et al. 1990

Antivir Chem Chemother

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Crystallographic studies have shown that, in the solid state, nucleosides active against the human immunodeficiency virus (HIV) generally exhibit moderate to extreme S-type furanose conformations (pseudorotational phase angle up to 215°). Following this lead, it is shown that using principles of conformational analysis, one can rationalize the activity or inactivity of other nucleoside analogues (including many not yet studied by X-ray methods) in terms of the effects of substituents on the furanose ring conformation. An analysis of the various 1,4 interactions of the O4′ lone pairs, O4′ itself, and the substituents on C2′ and C3′ shows that S-type conformations are stabilized (relative to N-type) in all the active ribose analogues, whereas this effect is absent in most inactive compounds. The gauche effect is a major determinant of activity, and the O4′ lone pairs, which have been neglected in many previous force field studies, may also be involved in stabilizing extreme S-type conformations. In such conformations (particularly for P > 180°) the + sc orientation of O5′ is destabilized, increasing access to the ap orientation, which may be more favourable for activity.

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Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Cited by 42 publications

References 24 publications

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹

Stereoelectronic effects of modified purine bases on the sugar conformation of nucleosides: pyrrolo[2,3-d]pyrimidines

A Stereochemical Rationale for the Activity of Anti-HIV Nucleosides

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Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation

Cited by 42 publications

References 24 publications

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases1

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases1

Stereoelectronic effects of modified purine bases on the sugar conformation of nucleosides: pyrrolo[2,3-d]pyrimidines

A Stereochemical Rationale for the Activity of Anti-HIV Nucleosides

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Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹

Deoxygenative [1,2]-Hydride Shift Rearrangements in Nucleoside and Sugar Chemistry: Analogy with the [1,2]-Electron Shift in the Deoxygenation of Ribonucleotides by Ribonucleotide Reductases¹