Synthesis of N6,N6‐Dialkyladenine Nucleosides Using Hexaalkylphosphorus Triamides Produced in Situ

Lakshman, Mahesh K.; Choudhury, Asad; Bae, Suyeal; Rochttis, Eliezer; Pradhan, Padmanava; Kumar, Amit

doi:10.1002/ejoc.200800752

Cited by 12 publications

(15 citation statements)

References 60 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This was indeed the case and not only were we able to synthesize O 6 -(benzotriazol-1-yl)inosine analogues, but we have been able to utilize the underlying chemistry to load inosine and 2′-deoxyinosine onto a polymer linker 16,17. The intermediacy of nucleoside phosphonium salts has also proven important in our recently described N 2-modification of 2′-deoxyguanosine,18 and in chemistry leading to N , N -modified adenosine analogues via reaction of protected inosine and 2′-deoxyinosine with hexaalkylphosphorus triamides produced in situ and I 2 19. In this paper, we report our findings on the synthesis of O 6 -(benzotriazol-1-yl)guanosine and 2′-deoxyguanosine, and their applications leading to C-6 modified 2-amino purine nucleoside analogues.…”

Section: Introductionmentioning

confidence: 99%

A simple method for C-6 modification of guanine nucleosides

Lakshman

Frank

2009

Org. Biomol. Chem.

Self Cite

View full text Add to dashboard Cite

A facile method for the introduction of various substituents at the C-6 position of guanosine and 2′-deoxyguanosine is reported. In a simple, 1-step transformation, tert-butyldimethylsilyl protected guanosine and 2′-deoxyguanosine were converted to the O 6 -(benzotriazol-1-yl) derivatives via reaction with 1H-benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The easily isolated, stable and storable, O 6 -(benzotriazol-1-yl) guanosine derivatives upon exposure to range of nucleophiles, under appropriate conditions, led to the C-6 modified 2-amino purine nucleoside analogues in good yields.

show abstract

Section: Introductionmentioning

confidence: 99%

A simple method for C-6 modification of guanine nucleosides

Lakshman

Frank

2009

Org. Biomol. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Formation of compound 37 is not entirely unanticipated, as we have previously observed its formation in reactions of HMPT and I 2 . 34 ( c ) In variations of the procedure described in ( b ), PPh 3 was used in place of HMPT, and reactions were conducted at room temperature and at 45 °C. In both reactions dichlorobenzotriazole 35 was formed and significant amounts of the nucleoside precursor were left unreacted.…”

Section: Resultsmentioning

confidence: 99%

A novel bis(pinacolato)diboron-mediated N–O bond deoxygenative route to C6 benzotriazolyl purine nucleoside derivatives

et al. 2016

Self Cite

View full text Add to dashboard Cite

Reaction of amide bonds in t-butyldimethylsilyl-protected inosine, 2′-deoxyinosine, guanosine, 2′-deoxyguanosine, and 2-phenylinosine with commercially available peptide-coupling agents (benzotriazol-1H-yloxy)tris(dimethylaminophosphonium) hexafluorophosphate (BOP), (6-chloro-benzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophosphate (PyClocK), and (7-azabenzotriazol-1H-yloxy)trispyrrolidinophosphonium hexafluorophospate (PyAOP) gave the corresponding O6-(benzotriazol-1-yl) nucleoside analogues containing a C–O–N bond. Upon exposure to bis(pinacolato)diboron and base, the O6-(benzotriazol-1-yl) and O6-(6-chlorobenzotriazol-1-yl) purine nucleoside derivatives obtained from BOP and PyClocK, respectively, underwent N–O bond reduction and C–N bond formation, leading to the corresponding C6 benzotriazolyl purine nucleoside analogues. In contrast, the 7-azabenzotriazolyloxy purine nucleoside derivatives did not undergo efficient deoxygenation, but gave unsymmetrical nucleoside dimers instead. This is consistent with a prior report on the slow reduction of 1-hydroxy-1H-4-aza and 1-hydroxy-1H-7-azabenzotriazoles. Because of the limited number of commercial benzotriazole-based peptide coupling agents, and to show applicability of the method when such coupling agents are unavailable, 1-hydroxy-1H-5,6-dichlorobenzotriazole was synthesized. Using this compound, silyl-protected inosine and 2′-deoxyinosine were converted to the O6-(5,6-dichlorobenzotriazol-1-yl) derivatives via in situ amide activation with PyBroP. The O6-(5,6-dichlorobenzotriazol-1-yl) purine nucleosides so obtained also underwent smooth reduction to afford the corresponding C6 5,6-dichlorobenzotriazolyl purine nucleoside derivatives. A total of 13 examples were studied with successful reactions occurring in 11 cases (the azabenzotriazole derivatives, mentioned above, being the only unreactive entities). To understand whether these reactions are intra or intermolecular processes, a crossover experiment was conducted. The results of this experiment as well as those from reactions conducted in the absence of bis(pinacolato)diboron and in the presence of water indicate that detachment of the benzotriazoloxy group from the nucleoside likely occurs, followed by reduction, and reattachment of the ensuing benzotriazole, leading to products.

show abstract

“…[23] A HAPT was used to activate the C(6) carbonyl group in compounds 40a and 40b, followed by displacement with amines or imidazole. The imidazolylpurine derivatives 41a and 41b were obtained in 67 and 86 % yields, respectively.…”

Section: Reactions Under Appel Conditions For the Synthesis Of C(6)-lmentioning

confidence: 99%

Synthesis and Applications of Azolylpurine and Azolylpurine Nucleoside Derivatives

2015

View full text Add to dashboard Cite

Azolylpurines and azolylpurine nucleosides have important medicinal and biological applications. They are used as adenosine receptor agonists and antagonists and also as antivirals. Several compounds of this class exhibit fluorescent properties that can be applied in biological chemistry. This review summarizes and classifies all reported classes of purine‐azole conjugates, strategies for their syntheses, and suggestions of compound classes yet to be synthesized. Synthetic methodologies directed towards purine–azole conjugates, including SNAr reactions, cyclizations of amino‐ or hydrazinylpurines, and transition‐metal‐catalyzed cross‐coupling reactions, are discussed, as well as the use of selected azolylpurine derivatives as synthetic intermediates.

show abstract

Synthesis of N⁶,N⁶‐Dialkyladenine Nucleosides Using Hexaalkylphosphorus Triamides Produced in Situ

Cited by 12 publications

References 60 publications

A simple method for C-6 modification of guanine nucleosides

A simple method for C-6 modification of guanine nucleosides

A novel bis(pinacolato)diboron-mediated N–O bond deoxygenative route to C6 benzotriazolyl purine nucleoside derivatives

Synthesis and Applications of Azolylpurine and Azolylpurine Nucleoside Derivatives

Contact Info

Product

Resources

About