29204-54-4

Upstream product

• 2004-06-0 6-Chloropurine riboside 
• 106-49-0 p-toluidine 
• 58-63-9 Inosine 
• 927818-53-9 O⁶-(benzotriazol-1-yl)inosine 

Relevant academic research and scientific papers

O6-(benzotriazol-1-yl)inosine derivatives: Easily synthesized, reactive nucleosides

A novel class of O6-(benzotriazol-1-yl)inosine as well as the corresponding 2′-deoxy derivatives can be conveniently prepared by a reaction between sugar-protected or -unprotected inosine or 2′- deoxyinosine nucleosides and 1H-benzotriazol-1-yloxy-tris(dimethylamino) phosphonium hexafluorophosphate (BOP). The reaction appears to proceed via a nucleoside phosphonium salt, and in the absence of any additional nucleophile, the released 1-hydroxybenzotriazole undergoes reaction with the formed phosphonium salt leading to the requisite O6-(benzotriazol-1-yl) inosine or 2′-deoxyinosine derivatives. Isolation and characterization of the phosphonium salt as well as analysis by 31P{1H} NMR appear to be consistent with this reaction pathway. The resulting O 6-(benzotriazol-1-yl)inosine derivatives are effective as electrophilic nucleosides, undergoing facile reactions with a variety of nucleophiles such as alcohols, phenols, amines, and a thiol. Unusual and challenging nucleoside derivatives such as an aryl-bridged dimer, a nucleoside-amino acid conjugate, and a nucleoside- nucleoside dimer have also been synthesized from the O6-(benzotriazol-1-yl)-2′- deoxyinosine derivative. Finally, a fully protected DNA building block, the O6-(benzotriazol-1-yl)-2′-deoxyinosine 5′-O-DMT 3′-O-phosphoramidite, has been prepared and a preliminary evaluation of its use for DNA modification has been performed. Results from these studies indicate several important facts: A single, simple methodological approach provides a class of stable, isolable ribo and 2′-deoxyribonucleoside derivatives that possess excellent reactivity for SNAr chemistry with a wide range of nucleophiles. Also, a benzotriazolyl nucleoside phosphoramidite appears to be a suitable reagent for incorporation into DNA for purposes of site-specific DNA modification.

Palladium-catalyzed aryl amination reactions of 6-bromo- and 6-chloropurine nucleosides

Palladium-catalyzed C-N bond forming reactions of 6-bromo- as well as 6-chloropurine ribonucleosides and the 2′-deoxy analogues with arylamines are described. Efficient conversions were observed with palladium(II) acetate/Xantphos/cesium carbonate, in toluene at 100°C. Reactions of the bromonucleoside derivatives could be conducted at a lowered catalytic loading [5 mol% Pd(OAc)2/7.5 mol% Xantphos], whereas good product yields were obtained with a higher catalyst load [10mol% Pd(OAc)2/ 15 mol% Xantphos] when the chloro analogue was employed. Among the examples evaluated, silyl protection for the hydroxy groups appears better as compared to acetyl. The methodology has been evaluated via reactions with a variety of arylamines and by synthesis of biologically relevant deoxyadenosine and adenosine dimers. This is the first detailed analysis of aryl amination reactions of 6-chloropurine nucleosides, and comparison of the two halogenated nucleoside substrates.

A highly facile and efficient one-step synthesis of N6-adenosine and N6-2′-deoxyadenosine derivatives

(Chemical Equation Presented) A highly facile and efficient one-step synthesis of N6-adenosine and N6-2′-deoxyadenosine derivatives has been developed. Treatment of inosine or 2′-deoxyinosine, without protection of sugar hydroxyl groups, with alkyl or arylamines, in the presence of BOP and DIPEA in DMF, led to the formation of N6- adenosine and N6-2′-deoxyadenosine derivatives in good to excellent yields. Carcinogenic polyaromatic hydrocarbon (PAH) N 6-2′-deoxyadenosine adduct 10 and a rare DNA constituent 11 were thus synthesized directly from 2′-deoxyinosine both in 98% yield.