Synthesis of 5‐/8‐Halogenated or Ethynylated Lipophilic Nucleobases as Potential Synthetic Intermediates for Supramolec­ular Chemistry

Abstract

El acceso a la versión del editor puede requerir la suscripción del recurso Access to the published version may require subscription Synthesis of 5-/8-Halogenated or Ethynylated Lipophilic Nucleobases as Potential Synthetic Intermediates for Supramolecular ChemistryNerea Bilbao, [a] Violeta Vázquez-González, [a] M. Teresa Aranda, [a] and David González-Rodríguez* [a] Abstract: A series of lipophilic nucleobases that are substituted at the 5-(pyrimidines) or 8-position (purines) with either a halogen atom or a terminal triple bond have been synthesized. The sequences and reactions studied in this work, which mainly comprise halogenation, alkylation, Sonogashira coupling, and trimethylsilylacetylene deprotection, have been carefully optimized in order to reach the final compounds in the most straightforward, convenient way and with the maximum purity and yield. These compounds include cytosine, isocytosine and uracil as pyrimidine heterocycles, and guanine, isoguanine, and 2-aminoadenine as complementary purine bases.Variability was introduced at the N-1/N-9 positions of these pyrimidine/purine nucleobases, which were functionalized with alkyl or benzyl groups, as well as with protected amine or carboxylic acid substituents. The molecules prepared constitute a useful collection of synthetic intermediates in the field of chemical self-assembly.

Functionalized Silver‐Ion‐Mediated α‐dC/β‐dC Hybrid Base Pairs with Exceptional Stability: α‐d‐5‐Iodo‐2′‐Deoxycytidine and Its Octadiynyl Derivative in Metal DNA

“… Synthesis of 5‐iodo‐ α ‐dC derivatives. i) I 2 , HIO 3 , AcOH, 40 °C, 16 h; ii) HMDS, TMSCl, reflux 5–6 h; iii) addition of Hoffer's sugar ( 7 ), pyridine, CH 2 Cl 2 , rt, 24 h; iv) NaOCH 3 , CH 3 OH, rt, 20 min; HCl neutralized; v) DMT‐Cl, pyridine, rt, 16 h; vi) AcOH, H 2 O, rt, 40 min; vii) (Bz) 2 O, DMF, rt, 4 d; viii) N , N ‐di‐ n‐ butylformamide dimethyl acetal, CH 3 OH, 55 °C, 4 h; ix) 2‐cyanoethyl diisopropylphosphoramidochloridite, DIPEA, CH 2 Cl 2 , rt, 1 h.…”

Impact of Conformational Effects on the Ring–Chain Equilibrium of Hydrogen‐Bonded Dinucleosides

“…Reaction solvents were thoroughly dried before use by using standard methods. The synthesis and characterization of G1 , C1 , U1 , G1 Alk2 , C1 Alk10 , G1 Alk10 , A1 Alk10 , and GC0 d have been recently reported by us. Compounds B′‐Me have been previously reported and their identity was checked only by means of 1 H NMR spectroscopic analysis.…”

Synthesis of Porphyrins Di‐ and Tetra‐Functionalized with Nucleobases

“…In order to increase the solubility of the nucleobases bearing ethynyl groups, a hexyl chain was introduced on the N1 position of pyrimidine derivatives and on the N9 site of purine derivatives. The targeted C5‐ethynyl‐functionalized pyrimidines, Ethynyl‐U and Ethynyl‐C , have been prepared following a methodology described by González‐Rodríguez et al [27] …”

“…The ethynyl‐functionalized nucleobases ( Ethynyl‐C , Ethynyl‐U , Ethynyl‐A , and Ethynyl‐G ) were reacted with zinc 5,15‐dibromo‐10,20‐dipentylporphyrin ZnPo3 [27] (Scheme 4) in a mixture of THF and triethylamine or a mixture of THF, DMF, and trimethylamine in the presence of bis(triphenylphosphine)palladium dichloride and copper iodide as catalysts.…”

“…All the starting reagents were obtained from commercial sources and used as received. The starting porphyrins: 5,15‐bis(4‐(bromomethyl)phenyl)‐10,20‐dimesitylporphyrin [23] ( Po1 ), 5,10,15,20‐tetrakis[4‐(bromomethyl)phenyl]porphyrin [26] ( Po2 ) and zinc 5,15‐dibromo‐10,20‐dipentylporphyrin [27] ( ZnPo3 ) were obtained following the described procedures. Brucker AC or AV‐300, AV‐400 or AV‐500 spectrometer was used to record NMR spectra at room temperature with the deuterated solvent as the internal reference.…”