Directed glycosidation of 8-bromoadenine. Synthesis and reactions of 8-substituted 3-glycosyladenine derivatives

Tindall, Charles G.; Robins, Roland K.; Tolman, Richard L.; Hutzenlaub, Wolfgang

doi:10.1021/jo00798a003

Cited by 26 publications

(13 citation statements)

References 4 publications

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“…The ESI-MS mass value (m/z = 270, M+H + for the 1′- 13 C substituted species) corresponds to [1′- 13 C]N3-isoinosine (but does not distinguish it from [1′- 13 C]inosine or [1′- 13 C]N7-isoinosine). UV-spectral properties at pH 1, 7, and 11 matched published findings for N3-isoinosine and are distinct from those reported for inosine and N7-isoinosine (Table S3) (Lehikoinen, et al, 1989; Montgomery and Thomas, 1969; Tindall, et al, 1972; Wolfenden, et al, 1966). The 1 H NMR spectrum of this isolated product agreed with the published chemical shift data for authentic N3-isoinosine but not for inosine or N7-isoinosine (Table S3) (Chenon, et al, 1975a; Lehikoinen, et al, 1989; Tindall, et al, 1972).…”

Section: Resultssupporting

confidence: 80%

“…The 1 H NMR spectra of [1′- 13 C]inosine with native PNP showed two new downfield singlets with chemical shifts of 8.55 and 8.18 ppm and another doublet of doublets with a chemical shift of 6.28 ppm between ∼3-6 and 24 h (Figure 4-II). The chemical shifts resemble those reported for the chemically synthesized N3-isomer of inosine (3-β- d -ribofuranosyl hypoxanthine or N3-isoinosine) [5] (s δ 8.67 or 8.59, s δ 8.32 or 8.25 and d δ 5.98 or 5.87 for H-8, H-2 and H-1′, respectively, in d 6 , DMSO) (Lehikoinen, et al, 1989; Tindall, et al, 1972). The rate of isomerization was approximately 1 × 10 -3 s -1 (Table 1).…”

Section: Resultssupporting

confidence: 71%

“…Spectra were processed with an exponential window function of 1 Hz. Spectra were assigned as described previously (Dorman and Roberts, 1970; Teijeira, et al, 1997; Tindall, et al, 1972). …”

Section: Methodsmentioning

confidence: 99%

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Ribocation Transition State Capture and Rebound in Human Purine Nucleoside Phosphorylase

Ghanem

Murkin

Schramm

2009

Chemistry & Biology

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Summary Purine nucleoside phosphorylase (PNP) catalyzes the phosphorolysis of 6-oxy-purine nucleosides to the corresponding purine base and α-d-ribose 1-phosphate. Its genetic loss causes a lethal T-cell deficiency. The highly reactive ribocation transition state of human PNP is protected from solvent by hydrophobic residues that sequester the catalytic site. The catalytic-site was enlarged by replacing individual catalytic site amino acids with glycine. Reactivity of the ribocation transition state was tested for capture by water and other nucleophiles. In the absence of phosphate, inosine is hydrolyzed by native, Y88G, F159G, H257G, and F200G enzymes. Phosphorolysis but not hydrolysis is detected when phosphate is bound. An unprecedented N9-to-N3 isomerization of inosine is catalyzed by H257G and F200G in the presence of phosphate and by all PNPs in the absence of phosphate. These results establish a ribocation lifetime too short to permit capture by water. An enlarged catalytic site permits ribocation formation with relaxed geometric constraints, permitting nucleophilic rebound and N3-inosine isomerization.

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Section: Resultssupporting

confidence: 80%

Section: Resultssupporting

confidence: 71%

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Ribocation Transition State Capture and Rebound in Human Purine Nucleoside Phosphorylase

Ghanem

Murkin

Schramm

2009

Chemistry & Biology

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“…The u.v.-absorption spectrum (Ammax 265 nm, Amin 230 nm) resembles that reported for the N-3 isomer (Amax 265 nm, Amin 232 nm) (Wolfenden et al, 1966), as does the 'H-n.m.r. spectrum: Tindall et al (1972) The line is that calculated for pH variation with pK2 values of 6.8 for inorganic phosphate and 6.2 for ribose 1-phosphate. 8 5.98 p.p.m., J1'_2' 6.0 Hz; we find H-8 s, 8 8.59 p.p.m., H-2 s, 8 8.25 p.p.m., and H-I' d, & 5.87 p.p.m., J1'_2' 6.4 Hz.…”

Section: Equilibrium Constantmentioning

confidence: 97%

Investigation of α-deuterium kinetic isotope effects on the purine nucleoside phosphorylase reaction by the equilibrium-perturbation technique

Lehikoinen

Sinnott

Krenitsky

1989

Biochemical Journal

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1. alpha-Deuterium kinetic isotope effects on the phosphorolysis of inosine catalysed by Escherichia coli purine nucleoside phosphorylase were measured by the equilibrium-perturbation technique, by using the change in absorbance at 250 nm (approx. 20%). 2. Values of 2H(V/K) of 1.13(9) at pH 5.0, 1.10(5) at pH 6.1, 1.09(4) at pH 7.3, 1.08 at pH 8.4 and 1.16(4) at pH 9.4 were obtained. 3. These are compared with literature alpha-deuterium kinetic isotope effects for this and related reactions. 4. The equilibrium constant, defined as [inosine].[H2PO4-]/[hypoxanthine] [alpha-Rib f OPO3H-], is 46 at 25 degrees C. 5. N-3-beta-D-Ribofuranosylhypoxanthine, an impurity in chemically synthesized inosine, is a substrate.

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“…Hydrolysis of the nucleoside 161 by the action of sodium methoxide in methanol gave 3-β-Dribofuranosyladenine 163 (yield 87%). The nucleoside 164 (yield 75%) was synthesized by treatment of the nucleoside 161 with nitrosyl chloride, and 3-β-D-ribofuranosylhypoxanthine (yield 91%) was obtained from the product by debenzoylation with ammonia in methanol [96]. In the reaction of 2,6,9-tri(triethylsilyl)xanthine 166a with acetobromoglucose in nitromethane in the presence of AgClO 4 3-β-D-glucopyranosylxanthine 167 was obtained [97].…”

Section: Trialkylsilyl Protectionmentioning

confidence: 99%

The use of protecting groups in the synthesis of purine derivatives (review)

Александрова

Кочергин²

2009

Chem Heterocycl Comp

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During the synthesis of derivatives of purine from amino-, hydroxy-, thio-, or chloropurines there is often a need at position 2, 6, 7, or 9 of the purine ring to insert a protecting group that can be removed after the necessary chemical operations and retained or replaced by another pharmacophoric group during the search for biologically active substances. ALKYL (ARALKYL) PROTECTION OF POSITION 7(9)The following basic rules were established on the basis of experimental data from a large number of papers and patents relating to the nucleophilic substitution of chloropurines, reported in the monographs [1, 2]: In the series of chloro-, dichloro-, and trichloropurines the most reactive is the chlorine atom at position 6, in second place is the chlorine atom at position 8, and in third place the chlorine atom at position 2 of the purine bicycle. This rule persists in the series of 7(9)-alkyl-2,6-, -2,8-, and -6,8-dichloropurines.In the series of 7(9)-alkyl-2,6,8-trichloropurines the order of nucleophilic substitution of the chlorine atoms changes. In these compounds, unlike 2,6,8-trichloropurine, the most vulnerable center for nucleophilic attack is the chlorine atom at position 8 and then the chlorine atom at position 6 of the purine ring. The chlorine atom at position 2 was and remains the most inert in the series of 7(9)-alkyl-2,6,8-trichloropurines.In the synthesis of 8-substituted purines from 2,6,8-trichloro-7-methylpurine (1) the founder of purine chemistry E. Fischer used the methyl group as protection. Thus, 2,6-dichloro-7-methylpurin-8-one (2) was obtained by the reaction of the trichloride 1 with KOH in aqueous solution at 20°C [3].

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Directed glycosidation of 8-bromoadenine. Synthesis and reactions of 8-substituted 3-glycosyladenine derivatives

Cited by 26 publications

References 4 publications

Ribocation Transition State Capture and Rebound in Human Purine Nucleoside Phosphorylase

Ribocation Transition State Capture and Rebound in Human Purine Nucleoside Phosphorylase

Investigation of α-deuterium kinetic isotope effects on the purine nucleoside phosphorylase reaction by the equilibrium-perturbation technique

The use of protecting groups in the synthesis of purine derivatives (review)

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