Synthesis of 5-alkynylated uracil–morpholino monomers using Sonogashira coupling

Paul, Subhojit; Nandi, Bappaditya; Pattanayak, Sankha; Sinha, Surajit

doi:10.1016/j.tetlet.2012.05.141

Cited by 15 publications

(11 citation statements)

References 18 publications

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“…This methodology, which has also been applied to the alkynylation of 8-bromopurines, is carried out using Pd(OAc) 2 (10 mol %) as palladium source, CuI as cocatalyst (10 mol %), and TXPTS [trisodium tri(2,4-dimethyl-5-sulfonatophenyl)phosphine] ( 257 ) as water-soluble ligand, allowing one to perform the reaction in aqueous acetonitrile at 65 °C as solvent. In addition, 5-iodo uracil-morpholino monomers have been recently 5-alkynylated with different terminal alkynes using Pd(PPh 3 ) 4 (10 mol %) as catalyst under copper-cocatalyzed reaction conditions …”

Section: Chemicals By Palladium-catalyzed C–c Coupling Reactions Of A...mentioning

confidence: 99%

Chemicals from Alkynes with Palladium Catalysts

2013

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Section: Chemicals By Palladium-catalyzed C–c Coupling Reactions Of A...mentioning

confidence: 99%

Chemicals from Alkynes with Palladium Catalysts

2013

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“…Our previously established conditions for the iodination of uridine monomer [25] with ICl/K 2 CO 3 in MeOH (Table 1, Entry 1) failed miserably to give the desired product 3: we instead isolated the unreacted starting material 2 (20 %) and an assortment of unidentified side products. When Ag 2 CO 3 was used as a base (Table 1, Entry 2) the iodo compound 3 was obtained in very poor yield along with the detritylated monomer, unreacted starting material, and several other unidentified side products.…”

Section: Synthesis Of the Morpholino-modified 5-iodocytidine Nucleosidementioning

confidence: 98%

“…Many such C-modified nucleoside triphosphates can be enzymatically incorporated into oligonucleotides. [25] Here we describe the synthesis of 5-substituted cytidine and 8-substituted adenosine and guanosine morpholino monomers from the corresponding halo derivatives by means of Sonogashira, Suzuki, and Heck coupling reactions. [22] Incorporation of a propyne group in a nucleobase is known to provide better duplex stability in DNA.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Nucleobase‐Functionalized Morpholino‐Modified Nucleoside Monomers Through Palladium‐Catalyzed Cross‐Coupling Reactions

Nandi¹,

Pattanayak²,

Paul³

et al. 2013

Eur J Org Chem

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Morpholino‐modified nucleoside analogues have widespread applications in developmental biology. To achieve nucleobase‐functionalized forms of morpholino nucleosides, syntheses of 5‐substituted cytidine, 8‐substituted adenosine, and 8‐substituted guanosine morpholino nucleoside monomers are described for the first time. The syntheses are based on the use of 5‐iodocytidine, 8‐bromoadenosine, and 8‐bromoguanosine morpholino nucleosides as the key starting materials. These iodo or bromo derivatives have also been synthesized for the first time. Palladium‐mediated cross‐coupling reactions (Sonogashira, Suzuki, and Heck) were then employed with the halo derivatives to accomplish the substitutions. Different reaction conditions for C, A, and G were standardized to achieve the conversions. The strategy was devised in such a way that the useful N‐trityl protecting groups remain at the end. The catalyst combinations used for Sonogashira, Suzuki, and Heck reactions were Pd(PPh3)2Cl2·CuI, Pd(dppf)Cl2·CH2Cl2, and Pd(OAc)2, respectively. Heck coupling between 5‐iodocytidine monomer and methyl acrylate worked well, whereas with acrylonitrile the exocyclic amine of cytidine was found to form the aza‐Michael adduct. In this context, treatment of iodocytidine with methyl acrylate under two different sets of conditions was found to produce either the Michael addition product or the Heck coupling product. Four of the functionalized morpholino monomers have been further confirmed by single‐crystal X‐ray structural analysis. All of these functionalized monomers were obtained in good to excellent overall yields.

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“…27,28 Though the photophysical properties of nucleoside monomers are known in the literature, 5 the same is not reported in the case of morpholino monomers. As a part of our project toward the synthesis of morpholino monomers 29,30 and morpholino oligomers, 31 herein we report the synthesis, photophysical studies and self-assembly into submicron rings of functionalized uracil morpholino monomers which, to the best of our knowledge, is the first report. In addition, we reveal some insight into the mechanism of the formation of rings.…”

mentioning

confidence: 98%

“…Nucleoside monomers 3, 4, 5 and 6 were synthesized from 1 through Sonogashira coupling with appropriate aryl alkynes according to our reported procedure in good to excellent yields (Scheme 1). 29 The UV-Vis absorption spectra of compounds 3 to 6 were measured in chloroform (Fig. 1a).…”

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confidence: 99%