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Nucleoside Modification with Boron Clusters and Their Metal Complexes

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Abstract
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Abstract

General methods for the synthesis of nucleosides modified with borane clusters and metallacarborane complexes are presented. These include: (1) the click chemistry approach based on Huisgen 1,3?dipolar cycloaddition and (2) tethering of the metallacarborane group to the aglycone of a nucleoside via a dioxane ring opening in oxonium metallacarborane derivatives. The proposed methodologies broaden the availability of nucleoside?borane cluster conjugates and open up new areas for their applications. Curr. Protoc. Nucleic Acid Chem. 38:4.37.1?4.37.26. © 2009 by John Wiley & Sons, Inc.

Keywords: boron clusters; metal complexes; click chemistry; nucleosides; bioorganic?inorganic materials

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Introduction
Basic Protocol 1: Preparation of Nucleoside‐Boron Cluster Conjugates via Click Chemical Ligation Method
Basic Protocol 2: Preparation of Nucleoside‐Boron Cluster Conjugates via Cyclic Ether Ring Opening in Cyclic Ether Boron Cluster Oxonium Adducts
Commentary
Literature Cited
Figures

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Basic Protocol 1: Preparation of Nucleoside‐Boron Cluster Conjugates via Click Chemical Ligation Method Materials

10‐Dioxane‐7,8‐dicarba‐nido ‐undecaborane zwitterion ( S.11 ) (J. Plešek, pers. comm.)
Sodium azide, pure
Dimethylformamide, anhydrous, 99.5% pure
Methylene chloride (CH 2 Cl 2 ), analytical grade
Methanol (CH 3 OH), analytical grade
Silica gel 60 (230 to 400 mesh)
PdCl 2
8‐Dioxane‐[3‐cobalt bis(1,2‐dicarbollide)] zwitterion ( S.13 ) or 8‐dioxane‐[3‐iron bis(1,2‐dicarbollide)] zwitterion ( S.14 )
60% sodium hydride (NaH) suspension in mineral oil
Propargyl alcohol, 99% pure
Toluene, anhydrous, 99.7% pure
Argon gas
7,8‐Dicarba‐nido ‐undecaborane anion ( S.18 ) (Hawthorne et al., )
98% sulfuric acid
Dioxane, anhydrous
99% dimethyl sulfate
30% and 50% ethanol (EtOH), analytical grade
[3‐Iron bis(1,2‐dicarbollide)](‐1)ate anion ( S.20 ) (Hawthorne et al., ; Sivaev and Bregadze, )
Nitrogen gas
Benzene, analytical grade
Hexane, analytical grade
Pentynyl tosylate (Rong et al., )
Thymidine ( S.21 )
Potassium carbonate, analytical grade
Diethylene glycol di(p ‐toluenesulfonate) (Chen and Barker, )
tert ‐Butanol, analytical grade
Water, deionized (Millipore)
100 mM CuSO 4 ⋅5H 2 O
100 mM potassium ascorbate

TLC plates, 20 × 20–cm, pre‐coated with 0.2‐mm layer thickness silica gel 60 F254
Evaporator with vacuum (SpeedVac Plus SC110A Savant)
1.5 × 20–cm and 2.5 × 20–cm sintered glass columns
Magnetic stir bar and plate
Separatory funnel
Filter paper (e.g., Whatman)
80°C heating block
Reflux condenser
Sintered disc filter funnel (e.g., Schott G3)
10‐mL syringes
Water aspirator
Vacuum pump
Lyophilizer

Basic Protocol 2: Preparation of Nucleoside‐Boron Cluster Conjugates via Cyclic Ether Ring Opening in Cyclic Ether Boron Cluster Oxonium Adducts Materials

3′,5′‐protected 2′‐deoxyribonucleoside S.23 , S.26 , S.29 , or S.32 (0.80 mmol)
8‐dioxane‐[3‐cobalt bis(dicarbollide)] zwitterion ( S.13 )
Phosphorus (V) oxide (P 2 O 5 ), 98% pure
Anhydrous toluene
Argon gas
60% sodium hydride (NaH) suspension in mineral oil
Silica gel
Methylene chloride (CH 2 Cl 2 ), analytical grade
Acetonitrile (CH 3 CN), anhydrous
3′,5′‐protected 2′‐deoxyadenosine S.32
8‐dioxane‐[3‐iron bis(dicarbollide)] zwitterion S.14
2′‐Deoxyadenosine
2′‐Deoxycytidine
2′‐Deoxyguanosine
2′‐Deoxythymidine
Tetrahydrofuran (THF), anhydrous
1 M tetra‐n ‐butylammonium fluoride (TBAF)
Ethyl acetate (EtOAc), analytical grade, absolute
Magnesium sulfate (Mg 2 SO 4 ), anhydrous, pure

Flasks with stoppers
Vacuum oil pump
Magnetic stir bar and heating plate
Water aspirator with vacuum attached
3.5 × 15–cm glass chromatography columns

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Figure 4.37.1 Synthesis of libraries of nucleoside‐boron cluster conjugates via chemical ligation using nucleoside boron cluster acceptors and boron cluster donors. R1 = 7,8‐dicarba‐ nido ‐undecaborane‐10‐yl, R2 = 3‐cobalt bis(1,2‐dicarbollide‐8‐yl), R3 = 3‐iron bis(1,2‐dicarbollide‐8‐yl).

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Figure 4.37.2 Synthesis of boron cluster donors containing terminal azido or alkynyl group.

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Figure 4.37.3 Synthesis of boron cluster cyclic oxonium derivatives—convenient precursors of boron cluster donors in Huisgen's 1,3‐dipolar cycloaddition reaction.

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Figure 4.37.4 Synthesis of nucleoside boron cluster acceptors.

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Figure 4.37.5 Synthesis of pyrimidine nucleoside‐metallacarborane conjugates via cyclic ether ring opening in cyclic ether boron cluster adducts.

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Figure 4.37.6 Synthesis of purine nucleoside‐metallacarborane conjugates via cyclic ether ring opening in cyclic ether boron cluster adducts.

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Figure 4.37.7 UV/vis (95% EtOH) spectrum of the thymidine boron cluster conjugate S.7 . Characteristic absorption for metallacarborane moiety appears ∼310 nm.

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Figure 4.37.8 FT‐IR (KBr) spectrum of the thymidine boron cluster conjugate S.7 . Characteristic B–H stretch appears at 2562 cm–1 .

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Figure 4.37.9 1 H NMR (CD3 OH, 250MHz, 25°C, TMS) spectrum of the thymidine boron cluster conjugate S.7 .

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Figure 4.37.10 MS‐ESI spectrum of the thymidine boron cluster conjugate S.7 . m/z (%): molecular formula: calcd. for C23 H49 B18 CoN5 O7 761.2, found 762.0 (100) [M+1]– .

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Literature Cited

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