Conformation of two 4'-thio-2'-deoxynucleoside analogs studied by 5000-MHz proton NMR spectroscopy and x-ray crystallography.

Koole, Léo H.; Plavec, Janez; Liu, Hongying; Vincent, Beverly R.; Dyson, Michael R.; Coe, Paul L.; Walker, Richard; Hardy, G.; Rahim, S. G.; Chattopadhyaya, J.

doi:10.1021/ja00051a028

Cited by 52 publications

(42 citation statements)

References 1 publication

(3 reference statements)

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“…The H-6/H-2 0 NOE was larger than the H-6/H-1 0 NOE, as expected if the thymine moiety preferentially populates the anti-conformation around the C-1 0 -N1 bond, as shown to be the case for the related 2 0 -deoxy-4 0 -thio system. 20 Under the optimized conditions, the treatment of selenoxide 15 with trimethylsilylated uracil gave the selenouridine derivative 18 in 56% yield, with complete b-stereoselectivity (Scheme 6). The TBS and acetonide protecting groups were removed in good yield by heating at reflux with 60% aqueous acetic acid for 30 min.…”

Section: Resultsmentioning

confidence: 99%

“…Water (30 mL) was added and removed under reduced pressure to remove the last of the HOAc. This crude product was purified by a silica gel column, eluted with CH 2 Cl 2 / MeOH (10:1) to give 17 as a pale tan-colored solid (20) N-Acetylcytosine (0.869 g, 5.68 mmol) was silylated using TMSOTf (3.1 mL, 17.04 mmol) and Et 3 N (1.2 mL, 8.52 mmol) in toluene (10 mL) according to the procedure of Matsuda 15 for the silylation of uracil. A solution of selenoxide 15 (1.04 g, 2.84 mmol) in dry CH 2 Cl 2 (10 mL) was added dropwise to the solution of the trimethylsilylated cytosine in toluene/CH 2 Cl 2 (2:1, 12 mL) at 0°C.…”

Section: -O-t-butyldimethylsilyl-23-di-o-isopropylidene-14-anhydromentioning

confidence: 99%

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Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

Jayakanthan

Johnston

Pinto

2008

Carbohydrate Research

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Section: Resultsmentioning

confidence: 99%

Section: -O-t-butyldimethylsilyl-23-di-o-isopropylidene-14-anhydromentioning

confidence: 99%

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

Jayakanthan

Johnston

Pinto

2008

Carbohydrate Research

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“…PET proliferation imaging should thus have an impact on oncology as a noninvasive clinical approach, and the present study demonstrated the high potential of 11 C-4DST. The structure of 11 C-4DST has the 49-oxo of thymidine replaced by 49-sulfur, so as to closely resemble the structure of thymidine (16). An in vitro study proved that 3 H-4DST is incorporated into DNA (17), and 14 C-4DST was confirmed to show metabolism similar to that of thymidine, maintaining stability in the blood (9,10).…”

Section: Discussionmentioning

confidence: 98%

4′-[Methyl-¹¹C]-Thiothymidine PET/CT for Proliferation Imaging in Non–Small Cell Lung Cancer

Minamimoto¹,

Toyohara²,

Seike³

et al. 2011

J Nucl Med

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A new tracer, 49-[methyl-11 C]-thiothymidine ( 11 C-4DST), has been developed as an in vivo cell proliferation marker based on the DNA incorporation method. This study evaluated the potential of 11 C-4DST PET/CT for imaging proliferation in nonsmall cell lung cancer (NSCLC), compared with 18 F-FDG PET/ CT. Methods: Eighteen patients with lung lesions were examined by PET/CT using 11 C-4DST and 18 F-FDG. We constructed decay-corrected time-activity curves of 9 major regions as the mean standardized uptake value. We then compared the maximum standardized uptake value (SUVmax) of lung tumors on both 11 C-4DST and 18 F-FDG PET/CT with the Ki-67 index of cellular proliferation and with CD31-positive vessels as a marker of angiogenesis in surgical pathology. Results: NSCLC was pathologically confirmed in 19 lesions of 18 patients. Physiologic accumulation of 11 C-4DST was high in liver, kidney, and bone marrow and low in aorta, brain, lung, and myocardium. Biodistribution of 11 C-4DST was almost stable by 20 min after injection of 11 C-4DST. Mean 11 C-4DST SUVmax for lung cancer was 2.9 6 1.0 (range, 1.5-4.7), significantly different from mean 18 F-FDG SUVmax, which was 6.2 6 4.5 (range, 0.9-17.3; P , 0.001). The correlation coefficient between SUVmax and Ki-67 index was higher with 11 C-4DST (r 5 0.82) than with 18 F-FDG (r 5 0.71). The correlation coefficient between SUVmax and CD31 was low with both 11 C-4DST (r 5 0.21) and 18 F-FDG (r 5 0.21), showing no significant difference between the tracers. Conclusion: A higher correlation with proliferation of lung tumors was seen for 11 C-4DST than for 18 F-FDG. 11 C-4DST PET/CT may allow noninvasive imaging of DNA synthesis in NSCLC.

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“…In addition, we needed a series of low energy structures of various sugar puckers to calculate the coefficients used in the PSEUROT calculations (vide infra) as has been done previously for systems with bond lengths and angles that are possibly distorted from "standard" nucleoside values. [35][36][37] In addition, we could use ab initio data to qualitatively compare the chemical shifts of proton and fluorine atoms in this small group of vicinal difluoro nucleosides (vide infra).…”

Section: Theory: Ab Initio Calculationsmentioning

confidence: 99%

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

et al. 2008

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The conformations of three 2′,3′-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that the two vicinal fluorine atoms play in the puckering preferences of the furanose ring. Two of the compounds examined contained fluorine atoms in either the arabino or xylo dispositions at C2′ and C3′ of a 2′, 3′-dideoxyuridine system. The third compound also incorporated fluorine atoms in the xylo configuration on the furanose ring but was substituted with a 6-azauracil base in place of uracil. A battery of NMR experiments in D 2 O solution was used to identify conformational preferences primarily from coupling constant and NOE data. Both 1 H and 19 F NMR data were used to ascertain the preferred sugar pucker of the furanose ring through the use of the program PSEUROT. Compound-dependent parameters used in the PSEUROT calculations were newly derived from complete sets of conformations calculated from high-level ab initio methods. The solution and theoretical data were compared to the conformations of each molecule in the solid state. It was shown that both gauche and antiperiplanar effects may be operative to maintain a pseudodiaxial arrangement of the C2′and C3′ vicinal fluorine atoms. These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations.

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Conformation of two 4'-thio-2'-deoxynucleoside analogs studied by 5000-MHz proton NMR spectroscopy and x-ray crystallography.

Cited by 52 publications

References 1 publication

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

4′-[Methyl-¹¹C]-Thiothymidine PET/CT for Proliferation Imaging in Non–Small Cell Lung Cancer

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

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Conformation of two 4'-thio-2'-deoxynucleoside analogs studied by 5000-MHz proton NMR spectroscopy and x-ray crystallography.

Cited by 52 publications

References 1 publication

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

Stereoselective synthesis of 4′-selenonucleosides using the Pummerer glycosylation reaction

4′-[Methyl-11C]-Thiothymidine PET/CT for Proliferation Imaging in Non–Small Cell Lung Cancer

Comprehensive Structural Studies of 2′,3′-Difluorinated Nucleosides: Comparison of Theory, Solution, and Solid State

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4′-[Methyl-¹¹C]-Thiothymidine PET/CT for Proliferation Imaging in Non–Small Cell Lung Cancer